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Sample records for time intranasal vaccination

  1. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    Science.gov (United States)

    2003-01-01

    submitting a licence application in Europe, a $US27.5 million payment for approval of a refrigerator-stable liquid formulation of FluMist and as much as $US50 million for licensing of FluMist internationally. In July 2003 MedImmune announced that it had received approximately $US28 million in milestone payments during Q2 of 2003 for the approval of FluMist. CSL Ltd of Australia will collaborate on the development, sale and distribution of MedImmune Vaccine's vaccine in Australia, New Zealand and certain countries in the South Pacific. MedImmune is to acquire vaccine research programmes in respiratory syncytial virus and cytomegalovirus from MedImmune Vaccines. The company's primary interest is in FluMist. In May 2002, MedImmune licensed exclusive rights to Crucell's proprietary human cell line PER.C6 for use in its influenza vaccine programmes. On 11 March 2002, American Home Products changed its name and the names of its subsidiaries Wyeth-Ayerst and Wyeth-Lederle to Wyeth. Wyeth's vaccines division is called Wyeth Vaccines. On 29 September 2000, Aviron announced that it had been awarded a $US2.7 million Challenge Grant from NIAID for development of vaccines against pandemic strains of influenza based on FluMist intranasal technology. The cold-adapted live influenza vaccine has been widely evaluated in the US and Japan since 1975 in clinical trials involving several thousand people. Aviron completed phase II clinical trials in adults in the US and phase III trials in US children aged 15-71 months. Additional phase III trials in adults and the elderly are ongoing. Aviron also commenced phase III trials to test the safety of its intranasal live vaccine in children with moderate to severe asthma. The vaccine is delivered using the AccuSpray nasal delivery system by Becton Dickinson, which will supply the system for FluMist through the 2001-2002 influenza season under an agreement with Aviron made in August 1998. On 7 March 2000, Aviron announced that Wyeth-Lederle Vaccines

  2. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Directory of Open Access Journals (Sweden)

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  3. Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

    Science.gov (United States)

    Glickman, L T; Appel, M J

    1981-08-01

    Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

  4. Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate.

    Science.gov (United States)

    Ainai, Akira; Suzuki, Tadaki; Tamura, Shin-Ichi; Hasegawa, Hideki

    The effect of the current influenza vaccine, an inactivated virus vaccine administered by subcutaneous/intramuscular injection, is limited to reducing the morbidity and mortality associated with seasonal influenza outbreaks. Intranasal vaccination, by contrast, mimics natural infection and induces not only systemic IgG antibodies but also local secretory IgA (S-IgA) antibodies found on the surface of the mucosal epithelium in the upper respiratory tract. S-IgA antibodies are highly effective at preventing virus infection. Although the live attenuated influenza vaccine (LAIV) administered intranasally can induce local antibodies, this vaccine is restricted to healthy populations aged 2-49 years because of safety concerns associated with using live viruses in a vaccine. Instead of LAIV, an intranasal vaccine made with inactivated virus could be applied to high-risk populations, including infants and elderly adults. Normally, a mucosal adjuvant would be required to enhance the effect of intranasal vaccination with an inactivated influenza vaccine. However, we found that intranasal administration of a concentrated, whole inactivated influenza virus vaccine without any mucosal adjuvant was enough to induce local neutralizing S-IgA antibodies in the nasal epithelium of healthy individuals with some immunological memory for seasonal influenza viruses. This intranasal vaccine is a novel candidate that could improve on the current injectable vaccine or the LAIV for the prevention of seasonal influenza epidemics.

  5. Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

    NARCIS (Netherlands)

    Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

    Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often

  6. Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

    Science.gov (United States)

    Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki

    2016-01-01

    Influenza is a contagious, acute respiratory disease caused by the influenza virus. The mucosal lining in the host respiratory tract is not only the site of virus infection, but also the site of defense; it is at this site that the host immune response targets the virus and protects against reinfection. One of the most effective methods to prevent influenza is to induce specific antibody (Ab) responses in the respiratory tract by vaccination. Two types of influenza vaccines, intranasal live attenuated influenza virus (LAIV) vaccines and parenteral (injectable) inactivated vaccines, are currently used worldwide. These vaccines are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration. Live attenuated vaccines induce both secretory IgA (S-IgA) and serum IgG antibodies (Abs), whereas parenteral vaccines induce only serum IgG Abs. However, intranasal administration of inactivated vaccines together with an appropriate adjuvant induces both S-IgA and IgG Abs. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines revealed that nasal S-IgA Abs, a major immune component in the upper respiratory tract, reacted with homologous virus hemagglutinin (HA) and were highly cross-reactive with viral HA variants, resulting in protection and cross-protection against infection by both homologous and variant viruses, respectively. Serum-derived IgG Abs, which are present mainly in the lower respiratory tract, are less cross-reactive and cross-protective. In addition, our own clinical trials have shown that nasal-inactivated whole virus vaccines, including a built-in adjuvant (single-stranded RNA), induced serum hemagglutination inhibition (HI) Ab titers that fulfilled the EMA criteria for vaccine efficacy. The nasal-inactivated whole virus vaccines also induced high levels of nasal HI and neutralizing Ab titers, although we have not yet evaluated the nasal HI titers due to the lack of official criteria to establish efficacy based

  7. Virus detection by PCR following vaccination of naive calves with intranasal or injectable multivalent modified-live viral vaccines.

    Science.gov (United States)

    Walz, Paul H; Newcomer, Benjamin W; Riddell, Kay P; Scruggs, Daniel W; Cortese, Victor S

    2017-09-01

    We evaluated duration of PCR-positive results following administration of modified-live viral (MLV) vaccines to beef calves. Twenty beef calves were randomly assigned to either group 1 and vaccinated intranasally with a MLV vaccine containing bovine alphaherpesvirus 1 (BoHV-1), bovine respiratory syncytial virus (BRSV), and bovine parainfluenza virus 3 (BPIV-3), or to group 2 and vaccinated subcutaneously with a MLV vaccine containing bovine viral diarrhea virus 1 and 2 (BVDV-1, -2), BoHV-1, BRSV, and BPIV-3. Deep nasopharyngeal swabs (NPS) and transtracheal washes (TTW) were collected from all calves, and whole blood was collected from group 2 calves and tested by PCR. In group 1, the proportions of calves that tested PCR-positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 0%, 100%, 100%, and 10%, respectively. In group 1 calves, 100% of calves became PCR-positive for BoHV-1 by day 3 post-vaccination and 100% of calves became PCR-positive for BRSV by day 7 post-vaccination. In group 2, the proportions of calves that tested positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 50%, 40%, 10%, and 0%, respectively. All threshold cycle (Ct) values were >30 in group 2 calves, irrespective of virus; however, Ct values PCR-positive results for BoHV-1 and BRSV. All calves were PCR-negative for all viruses after day 28. Following intranasal MLV viral vaccination, PCR results and Ct values for BRSV and BoHV-1 suggest that attempts to differentiate vaccine virus from natural infection is unreliable.

  8. Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

    Science.gov (United States)

    Pinto, Eduardo Fonseca; Pinheiro, Roberta Olmo; Rayol, Alice; Larraga, Vicente; Rossi-Bergmann, Bartira

    2004-01-01

    We have previously demonstrated that oral delivery of a disease-promoting particulated antigen of Leishmania amazonensis (LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 μg of LaAg and were challenged 1 week postvaccination with L. amazonensis developed delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-γ) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 μg/dose) had no effect. Interestingly, LACK DNA (30 μg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-γ. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA. PMID:15271911

  9. Efficacy of vaccination strategies against intranasal challenge with Brucella abortus in BALB/c mice.

    Science.gov (United States)

    Surendran, Naveen; Sriranganathan, Nammalwar; Lawler, Heather; Boyle, Stephen M; Hiltbold, Elizabeth M; Heid, Bettina; Zimmerman, Kurt; Witonsky, Sharon G

    2011-03-24

    Brucellosis is a zoonotic disease affecting 500,000 people worldwide annually. Inhalation of aerosol containing a pathogen is one of the major routes of disease transmission in humans. Currently there are no licensed human vaccines available. Brucella abortus strain RB51 is a USDA approved live attenuated vaccine against cattle brucellosis. In a mouse model, strain RB51 over-expressing superoxide dismutase (SOD) administered intraperitoneally (IP) has been shown to be more protective than strain RB51 against an IP challenge with B. abortus pathogenic strain 2308. However, there is lack of information on the ability of these vaccine strains to protect against intranasal challenge. With the long-term goal of developing a protective vaccine for animals and people against respiratory challenge of Brucella spp., we tested a number of different vaccination strategies against intranasal infection with strain 2308. We employed strains RB51 and RB51SOD to assess the efficacy of route, dose, and prime-boost strategies against strain 2308 challenge. Despite using multiple protocols to enhance mucosal and systemic protection, neither rough RB51 vaccine strains provided respiratory protection against intranasal pathogenic Brucella infection. However, intranasal (IN) administration of B. abortus vaccine strain 19 induced significant (p≤0.05) pulmonary clearance of strain 2308 upon IN challenge infection compared to saline. Further studies are necessary to address host-pathogen interaction in the lung microenvironment and elucidate immune mechanisms to enhance protection against aerosol infection. Published by Elsevier Ltd.

  10. Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.

    Science.gov (United States)

    Lankelma, Jacqueline M; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W; Trentelman, Jos J A; Weehuizen, Tassili A F; Ersöz, Jasmin; Roelofs, Joris J T H; Hovius, Joppe W; Wiersinga, W Joost; Bins, Adriaan D

    2017-11-17

    Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

  11. Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

    Science.gov (United States)

    Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

    2017-12-01

    Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

  12. Cross-protection conferred by immunization with an rOmpH-based intranasal fowl cholera vaccine.

    Science.gov (United States)

    Varinrak, Thanya; Poolperm, Pichayanut; Sawada, Takuo; Sthitmatee, Nattawooti

    2017-10-01

    A previous study demonstrated that a recombinant outer membrane protein H (rOmpH)-based intranasal fowl cholera vaccine elicited efficient homologous protection against the Pasteurella multocida strain X-73 (A:1) in chickens. The present study aimed to determine the cross-protectivity against heterologous P. multocida strains. The rOmpH was purified via electroelution and formulated with two kinds of adjuvants. The vaccine formulations in a total volume of 100 µl were 100 µg rOmpH with 3 µg of Escherichia coli enterotoxin B or 10 µg of CpG ODN2007. Chickens were assigned to three experimental groups depending on bacterial strain challenge exposure as well as three control groups. The chickens were immunized intranasally three times at three-week intervals. Challenge exposures were conducted by inoculation with homologous strain X-73 or heterologous strains P-1059 (A:3) or P-1662 (A:4) at four weeks after the final immunization. The specific antibody against rOmpH was produced in vaccinated birds. Sera IgY and secretory IgA antibody titres were significantly increased (P < 0.05) post-immunization. The stimulation index values of the vaccinated groups were significantly different from stimulation index values of the non-vaccinated groups (P < 0.05). Chicken survival rates after exposure to avian P. multocida strains ranged from 70% to 100%. There was no significant difference in protection between two kinds of adjuvants in vaccine formulations. Statistical analysis indicated no significant differences in protection among avian P. multocida strains challenge exposure. We conclude that an in-house rOmpH-based intranasal fowl cholera vaccine produced efficient cross-protectivity against heterologous strains of P. multocida.

  13. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

    Science.gov (United States)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

  14. Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

    Directory of Open Access Journals (Sweden)

    Asher Maroof

    2014-01-01

    Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

  15. Immune Responses of Dairy Cattle to Parainfluenza-3 Virus in Intranasal Infectious Bovine Rhinotracheitis-Parainfluenza-3 Virus Vaccines

    OpenAIRE

    Burroughs, A.L.; Morrill, J.L.; Bostwick, J.L.; Ridley, R.K.; Fryer, H.C.

    1982-01-01

    Two hundred and fifty dairy heifers were vaccinated at three to six months of age with an intranasal infectious bovine rhinotracheitis-parainfluenza-3 vaccine. Eighteen additional heifers were tested prior to vaccination and again three to four weeks after vaccination. Neither cell-mediated nor humoral immunity was significantly raised to parainfluenza-3 virus in either group of cattle.

  16. Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine.

    Science.gov (United States)

    Riddle, Mark S; Kaminski, Robert W; Williams, Carlos; Porter, Chad; Baqar, Shahida; Kordis, Alexis; Gilliland, Theron; Lapa, Joyce; Coughlin, Melissa; Soltis, Chris; Jones, Erica; Saunders, Jackie; Keiser, Paul B; Ranallo, Ryan T; Gormley, Robert; Nelson, Michael; Turbyfill, K Ross; Tribble, David; Oaks, Edwin V

    2011-09-16

    Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device. Volunteers (N=36) were randomized to receive vaccine via the Dolphin™ (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N=8) received the 240 μg dose via pipette. Vaccine safety was actively monitored and antigen-specific humoral and mucosal immune responses were determined. There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 μg dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin™ resulted in higher plasma and ASC immune responses as compared to pipette delivery. In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery. Published by Elsevier Ltd.

  17. Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1

    Directory of Open Access Journals (Sweden)

    Nya L. Fraleigh

    2016-08-01

    Full Text Available Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system. Our nicotine vaccine candidate was administered intranasally using the Neisseria meningitidis serogroup B Adjuvant Finlay Proteoliposome 1 (AFPL1 as a part of the delivery system. This system was designed to generate a robust immune response by stimulating IL-1β production through Toll-like receptor 4 (TLR4, a potent mechanism for mucosal immunity. The vaccine induced high antibody titers in mice sera in addition to inducing mucosal antibodies. The efficacy of our vaccine was demonstrated using in vivo challenge experiments with radioactive [3H]-nicotine, followed by an analysis of nicotine distribution in the lung, liver, blood and brain. Our results were encouraging as the nicotine concentration in the brain tissue of mice vaccinated with our candidate vaccine was four times lower than in non-vaccinated controls; suggesting that the anti-nicotine antibodies were able to block nicotine from crossing the blood brain barrier. In summary, we have developed a novel nicotine vaccine for the treatment of tobacco addiction by intranasal administration and also demonstrated that the AFPL1 can be used as a potential adjuvant for this vaccine design.

  18. Safety and Immunogenicity Testing of an Intranasal Group B Meningococcal Native Outer Membrane Vesicle Vaccine in Healthy Volunteers

    National Research Council Canada - National Science Library

    Drabick, Joseph

    1998-01-01

    An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain and tested in 32 healthy adult volunteers...

  19. Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit antigens.

    Science.gov (United States)

    Fan, Yuchen; Sahdev, Preety; Ochyl, Lukasz J; Akerberg, Jonathan; Moon, James J

    2015-06-28

    Here we report the development of a new cationic liposome-hyaluronic acid (HA) hybrid nanoparticle (NP) system and present our characterization of these NPs as an intranasal vaccine platform using a model antigen and F1-V, a candidate recombinant antigen for Yersinia pestis, the causative agent of plague. Incubation of cationic liposomes composed of DOTAP and DOPE with anionic HA biopolymer led to efficient ionic complexation and formation of homogenous liposome-polymer hybrid NPs, as evidenced by fluorescence resonance energy transfer, dynamic light scattering, and nanoparticle tracking analyses. Incorporation of cationic liposomes with thiolated HA allowed for facile surface decoration of NPs with thiol-PEG, resulting in the formation of DOTAP/HA core-PEG shell nanostructures. These NPs, termed DOTAP-HA NPs, exhibited improved colloidal stability and prolonged antigen release. In addition, cytotoxicity associated with DOTAP liposomes (LC50~0.2mg/ml) was significantly reduced by at least 20-fold with DOTAP-HA NPs (LC50>4mg/ml), as measured with bone marrow derived dendritic cells (BMDCs). Furthermore, NPs co-loaded with ovalbumin (OVA) and a molecular adjuvant, monophosphoryl lipid A (MPLA) promoted BMDC maturation and upregulation of co-stimulatory markers, including CD40, CD86, and MHC-II, and C57BL/6 mice vaccinated with NPs via intranasal route generated robust OVA-specific CD8(+) T cell and antibody responses. Importantly, intranasal vaccination with NPs co-loaded with F1-V and MPLA induced potent humoral immune responses with 11-, 23-, and 15-fold increases in F1-V-specific total IgG, IgG1, and IgG2c titers in immune sera by day 77, respectively, and induced balanced Th1/Th2 humoral immune responses, whereas mice immunized with the equivalent doses of soluble F1-V vaccine failed to achieve sero-conversion. Overall, these results suggest that liposome-polymer hybrid NPs may serve as a promising vaccine delivery platform for intranasal vaccination against Y

  20. Intranasal immunization with a formalin-inactivated human influenza A virus whole-virion vaccine alone and intranasal immunization with a split-virion vaccine with mucosal adjuvants show similar levels of cross-protection.

    Science.gov (United States)

    Okamoto, Shigefumi; Matsuoka, Sumiko; Takenaka, Nobuyuki; Haredy, Ahmad M; Tanimoto, Takeshi; Gomi, Yasuyuki; Ishikawa, Toyokazu; Akagi, Takami; Akashi, Mitsuru; Okuno, Yoshinobu; Mori, Yasuko; Yamanishi, Koichi

    2012-07-01

    The antigenicity of seasonal human influenza virus changes continuously; thus, a cross-protective influenza vaccine design needs to be established. Intranasal immunization with an influenza split-virion (SV) vaccine and a mucosal adjuvant induces cross-protection; however, no mucosal adjuvant has been assessed clinically. Formalin-inactivated intact human and avian viruses alone (without adjuvant) induce cross-protection against the highly pathogenic H5N1 avian influenza virus. However, it is unknown whether seasonal human influenza formalin-inactivated whole-virion (WV) vaccine alone induces cross-protection against strains within a subtype or in a different subtype of human influenza virus. Furthermore, there are few reports comparing the cross-protective efficacy of the WV vaccine and SV vaccine-mucosal adjuvant mixtures. Here, we found that the intranasal human influenza WV vaccine alone induced both the innate immune response and acquired immune response, resulting in cross-protection against drift variants within a subtype of human influenza virus. The cross-protective efficacy conferred by the WV vaccine in intranasally immunized mice was almost the same as that conferred by a mixture of SV vaccine and adjuvants. The level of cross-protective efficacy was correlated with the cross-reactive neutralizing antibody titer in the nasal wash and bronchoalveolar fluids. However, neither the SV vaccine with adjuvant nor the WV vaccine induced cross-reactive virus-specific cytotoxic T-lymphocyte activity. These results suggest that the intranasal human WV vaccine injection alone is effective against variants within a virus subtype, mainly through a humoral immune response, and that the cross-protection elicited by the WV vaccine and the SV vaccine plus mucosal adjuvants is similar.

  1. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    International Nuclear Information System (INIS)

    Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

    2013-01-01

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  2. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Science.gov (United States)

    Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

    2013-05-01

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  3. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

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    Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

    2013-05-15

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  4. IgA polymerization contributes to efficient virus neutralization on human upper respiratory mucosa after intranasal inactivated influenza vaccine administration.

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    Terauchi, Yoshihiko; Sano, Kaori; Ainai, Akira; Saito, Shinji; Taga, Yuki; Ogawa-Goto, Kiyoko; Tamura, Shin-Ichi; Odagiri, Takato; Tashiro, Masato; Fujieda, Mikiya; Suzuki, Tadaki; Hasegawa, Hideki

    2018-02-09

    Unlike the current injectable influenza vaccines, intranasally administered influenza vaccines induce influenza virus-specific IgA antibodies in the local respiratory mucosa as well as IgG antibodies in the systemic circulation. Our previous study showed that after five volunteers underwent intranasal administration with inactivated H3N2 or H5N1 vaccines, their IgA antibodies on the upper respiratory tract were present as monomers, dimers, and multimers (trimers and tetramers). Moreover, the multimers associated with the highest virus neutralizing activity. However, it has remained elusive whether a more practical intranasal vaccination strategy could induce the high-performance IgA multimers in the nasal mucosa. In the present study, volunteers were administered with two doses of the intranasal trivalent whole-virus inactivated influenza vaccine and showed that in nasal wash samples the amount of multimeric IgA correlated positively with virus neutralizing titers, indicating that the multimeric IgA antibodies play an important role in the antiviral activity at the nasal mucosa. Surface plasmon resonance analysis of the binding dynamics of nasal wash derived IgA monomers, dimers, and multimers against recombinant trimeric influenza virus HA showed that sample fractions containing IgA multimers dissociated from HA less well than sample fractions without IgA multimers. Thus, IgA multimers may "stick" to the antigen more tightly than the other structures. In summary, intranasal administration of two doses of multivalent inactivated influenza vaccines induced multimeric IgA. Multimerization of mucosal IgA antibodies conferred higher neutralizing activity against viruses in the nasal mucosa, possibly by increasing their cohesion to virus antigens. (243 words Limit: 250 words).

  5. Intranasal delivery of a bivalent norovirus vaccine formulated in an in situ gelling dry powder.

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    Jordan P Ball

    Full Text Available The global health community is beginning to understand the burden of norovirus-associated disease, which has a significant impact in both developed and developing countries. Norovirus virus like particle (VLP-based vaccines are currently under development and have been shown to elicit systemic and mucosal immune responses when delivered intranasally. In the present study, we describe the use of a dry powder formulation (GelVac™ with an in situ gelling polysaccharide (GelSite™ extracted from Aloe vera for nasal delivery of a bivalent vaccine formulation containing both GI and GII.4 norovirus VLPs. Dose-ranging studies were performed to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs and determine any antigenic interference. A dose-dependent increase in systemic and mucosal immunogenicity against each of the VLPs were observed as well as a boosting effect for each VLP after the second dosing. A total antigen dose of ≥50 μg of each GI and GII.4 VLPs was determined to be the maximally immunogenic dose in guinea pigs. The immunogenicity results of this bivalent formulation, taken together with previous work on monovalent GelVac™ norovirus vaccine formulation, provides a basis for future development of this norovirus VLP vaccine.

  6. Vaccination with Toxoplasma lysate antigen and CpG oligodeoxynucleotides: comparison of immune responses in intranasal versus intramuscular administrations.

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    EL-Malky, Mohamed A; Al-Harthi, Saeed A; Mohamed, Raafat T; EL Bali, Mohamed A; Saudy, Niveen S

    2014-06-01

    Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoan parasites on earth and highly prevalent in most warm-blooded vertebrates. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance in disease control. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T-helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against intracellular pathogen. In this study, we compare the immune responses of Toxoplasma susceptible C57BL/6 mice following intranasal and intramuscular vaccination with Toxoplasma lysate antigen (TLA) with or without CpG ODN as adjuvant. Immunized and control non-immunized mice were challenged with 85 cyst of the moderately virulent Beverley strain of T. gondii. Intranasal vaccination gave significantly a higher protection compared to other groups as indicated by prolonged survival and significantly reduced brain cyst burden (P intramuscular vaccination enhanced humoral immunity towards a type Th1 pattern characterized by a significant increase of specific IgG and Ig2a. Our results suggest that intranasal administration of CpG/TLA would provide a stable, pronounced, and effective vaccine against toxoplasmosis through stimulation of Th1 cellular immunity and mucosal IgA.

  7. Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects.

    Science.gov (United States)

    Treanor, John; Nolan, Carrie; O'Brien, Diane; Burt, David; Lowell, George; Linden, Janine; Fries, Louis

    2006-01-16

    Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.

  8. Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)-Structure, function and species differences.

    Science.gov (United States)

    Pabst, Reinhard

    2015-08-26

    The advantage of mucosal vaccination in viral and bacterial infections in different age groups is of enormous clinical relevance. The advantages and potential hazards of intranasal vaccination have always to be considered. The intranasal route for vaccination is very successful for some antigens. Specific adjuvants are necessary. In the nose of rodents there is a structured lymphoid tissue (nose-associated lymphoid tissue (NALT)). This abbreviation should not be used for nasopharynx-associated lymphoid tissue, as this includes parts of the tonsils. In children lymphoid tissue is more dispersed in the nose and not concentrated at the bottom of the dorsal nose ducts as in rodents. There are no data on organized lymphoid tissue in the nose of adults. In NALT of rodents there is a unique structure of adhesion molecule expression; the postnatal development and the different composition of T and B lymphocytes in comparison with Peyer's patches document the uniqueness of this lymphoid organ. There is also a mucosa in the nose with antigen-presenting dendritic cells. Thus, it is often unclear whether intranasal vaccination is initiated via NALT or the diffuse nasal mucosa. There are still many open questions e. g., which adjuvant is necessary for a specific virus, bacterium or other allergen, how many doses are critical for an effective nasal vaccination. Species differences are of major importance when extrapolating results from rodents to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Preclinical evaluation of a replication-deficient intranasal DeltaNS1 H5N1 influenza vaccine.

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    Julia Romanova

    Full Text Available BACKGROUND: We developed a novel intranasal influenza vaccine approach that is based on the construction of replication-deficient vaccine viruses that lack the entire NS1 gene (DeltaNS1 virus. We previously showed that these viruses undergo abortive replication in the respiratory tract of animals. The local release of type I interferons and other cytokines and chemokines in the upper respiratory tract may have a "self-adjuvant effect", in turn increasing vaccine immunogenicity. As a result, DeltaNS1 viruses elicit strong B- and T- cell mediated immune responses. METHODOLOGY/PRINCIPAL FINDINGS: We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine virus was constructed by reverse genetics in Vero cells, as a 5:3 reassortant, encoding four proteins HA, NA, M1, and M2 of the A/Vietnam/1203/04 virus while the remaining genes were derived from IVR-116. The HA cleavage site was modified in a trypsin dependent manner, serving as the second attenuation factor in addition to the deleted NS1 gene. The vaccine candidate was able to grow in the Vero cells that were cultivated in a serum free medium to titers exceeding 8 log(10 TCID(50/ml. The vaccine virus was replication deficient in interferon competent cells and did not lead to viral shedding in the vaccinated animals. The studies performed in three animal models confirmed the safety and immunogenicity of the vaccine. Intranasal immunization protected ferrets and mice from being infected with influenza H5 viruses of different clades. In a primate model (Macaca mulatta, one dose of vaccine delivered intranasally was sufficient for the induction of antibodies against homologous A/Vietnam/1203/04 and heterologous A/Indonesia/5/05 H5N1 strains. CONCLUSION/SIGNIFICANCE: Our findings show that intranasal immunization with the replication deficient H5N1 DeltaNS1 vaccine candidate is sufficient to induce a protective immune response against H5N1 viruses. This approach

  10. Mucosal vaccination with formalin-inactivated avian metapneumovirus subtype C does not protect turkeys following intranasal challenge.

    Science.gov (United States)

    Kapczynski, Darrell R; Perkins, Laura L; Sellers, Holly S

    2008-03-01

    Studies were performed to determine if mucosal vaccination with inactivated avian metapneumovirus (aMPV) subtype C protected turkey poults from clinical disease and virus replication following mucosal challenge. Decreases in clinical disease were not observed in vaccinated groups, and the vaccine failed to inhibit virus replication in the tracheas of 96% of vaccinated birds. Histopathologically, enhancement of pulmonary lesions following virus challenge was associated with birds receiving the inactivated aMPV vaccine compared to unvaccinated birds. As determined by an enzyme-linked immunosorbent assay (ELISA), all virus-challenged groups increased serum immunoglobulin (Ig) G and IgA antibody production against the virus following challenge; however, the unvaccinated aMPV-challenged group displayed the highest increases in virus-neutralizing antibody. On the basis of these results it is concluded that intranasal vaccination with inactivated aMPV does not induce protective immunity, reduce virus shedding, or result in decreased histopathologic lesions.

  11. Plasmid DNA Vaccine Co-Immunisation Modulates Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice.

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    Deborah F L King

    Full Text Available An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice.Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFNγ responses were preserved in co-immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity.These data suggest that while IN inoculation alone elicits both cellular and humoral responses, co-administration with homologous DNA vaccination can tailor these towards a more balanced Th1/Th2 phenotype modulating the cellular cytokine profile while eliciting high-levels of antigen-specific antibody. This work provides insights on how to generate differential immune responses within the same vaccination visit, and supports co-immunisation with DNA and protein by a mucosal route as a potential delivery strategy for HIV vaccines.

  12. Microneedle Vaccination Elicits Superior Protection and Antibody Response over Intranasal Vaccination against Swine-Origin Influenza A (H1N1 in Mice.

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    Ju-Hyung Shin

    Full Text Available Influenza is one of the critical infectious diseases globally and vaccination has been considered as the best way to prevent. In this study, immunogenicity and protection efficacy between intranasal (IN and microneedle (MN vaccination was compared using inactivated swine-origin influenza A/H1N1 virus vaccine. Mice were vaccinated by MN or IN administration with 1 μg of inactivated H1N1 virus vaccine. Antigen-specific antibody responses and hemagglutination-inhibition (HI titers were measured in all immunized sera after immunization. Five weeks after an immunization, a lethal challenge was performed to evaluate the protective efficacy. Furthermore, mice were vaccinated by IN administration with higher dosages (> 1 μg, analyzed in the same manner, and compared with 1 μg-vaccine-coated MN. Significantly higher antigen-specific antibody responses and HI titer were measured in sera in MN group than those in IN group. While 100% protection, slight weight loss, and reduced viral replication were observed in MN group, 0% survival rate were observed in IN group. As vaccine dose for IN vaccination increased, MN-immunized sera showed much higher antigen-specific antibody responses and HI titer than other IN groups. In addition, protective immunity of 1 μg-MN group was similar to those of 20- and 40 μg-IN groups. We conclude that MN vaccination showed more potential immune response and protection than IN vaccination at the same vaccine dosage.

  13. Responses of primary human nasal epithelial cells to EDIII-DENV stimulation: the first step to intranasal dengue vaccination.

    Science.gov (United States)

    Nantachit, Nattika; Sunintaboon, Panya; Ubol, Sukathida

    2016-08-18

    About half of the world's population are living in the endemic area of dengue viruses implying that a rapid-mass vaccination may be required. In addition, a major target of dengue vaccine are children, thus, a needle-free administration is more attractive. These problems may be overcome by the alternative route of vaccination such as topical, oral and intranasal vaccination. Here, we investigated the possibility to deliver a dengue immunogen intranasally, a painless route of vaccination. The tested immunogen was the domain III of dengue serotype-3 E protein (EDIII-D3) loaded into trimethyl chitosan nanoparticles (EDIII-D3 TMC NPs). The primary human nasal epithelial cells, HNEpCs, were used as an in vitro model for nasal responses. At tested concentrations, EDIII-D3 TMC NPs not only exerted no detectable toxicity toward HNEpC cultures but also efficiently delivered EDIII-D3 immunogens into HNEpCs. Moreover, HNEpCs quickly and strongly produced proinflammatory cytokines (IL-1β, IL-6, TNF-α), type-I IFN, the growth factors (GM-CSF, IL-7), the chemokines (MCP-1, MIP-1β, IL-8), Th1-related cytokines (IL-2, IL-12p70, IL-17, IFN-γ) and Th2-related cytokine (IL-4) in response to EDIII-D3 TMC NPs treatment. A potential mucosal delivery system for dengue immunogens was revealed and found to stimulate a strong local innate antiviral response which possibly leading to a systemic adaptive immunity.

  14. Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.

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    Shu-Ting Ren

    Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

  15. Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves.

    Science.gov (United States)

    Mansoor, Fawad; Earley, Bernadette; Cassidy, Joseph P; Markey, Bryan; Doherty, Simon; Welsh, Michael D

    2015-08-21

    There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. There was a significant (P administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak.

  16. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs

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    Santosh Dhakal

    2018-05-01

    Full Text Available Annually, swine influenza A virus (SwIAV causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs administered through intranasal (IN route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage antigens (KAg were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg. The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage. Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL fluids, and lung lysates that were reactive against homologous (H1N2, heterologous (H1N1, and heterosubtypic (H3N2 influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC 4] and BAL fluid (DPC 6 were significantly (p < 0.05 reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared

  17. Effectiveness of intranasal vaccination against Angiostrongylus costaricensis using a serine/threonine phosphatase 2 A synthetic peptide and recombinant antigens.

    Science.gov (United States)

    Solano-Parada, J; Gonzalez-Gonzalez, G; Torró, L M de Pablos; dos Santos, M F Brazil; Espino, A M; Burgos, M; Osuna, A

    2010-07-19

    Intranasal immunization was assayed in C57BL/6 mice against Angiostrongylus costaricensis using a synthetic and a recombinant peptide belonging to the catalytic region of the serine/threonine phosphatase 2 A (PP2A) of the parasite. Immunization was carried out with the synthetic peptide (SP) polymerized either with itself or with the beta fraction of the cholera toxin (CTB) and then enclosed in nanocapsules of phosphatidyl choline, cholesterol and Quil A (ISCOM). Another group of mice was immunized with recombinant peptide. Immunization consisted of two intranasal inoculations at two-week intervals, and the challenge with L3 larvae was made one month after the last vaccination. The effectiveness of immunization was evaluated 30 days after infection by analysis of the number of parasites in the arteries of the immunized mice, as well as by measuring spleen sizes in the experimental groups. The response induced was determined by identifying the isotypes of IgG as well as the IgE and IgA specific antigen response. The interleukins produced by the splenocyte culture of the different groups were assessed after exposing them to the peptide used in the immunization. From our results, 60%, 80%, and 100% protection against the A. costaricensis challenge was achieved in mice immunized with polymerized synthetic peptide in ISCOM, synthetic peptide polymerized with the CTB in ISCOM and inclusion bodies respectively. Splenomegaly was found to be less evident in the immunized mice than in the controls. A significant increase in IFN gamma and IL-17 levels was observed in the group with 100% protection. The results showed that vaccination through the nasal mucosa may constitute a useful method of immunization and result in a protective immune response against A. costaricensis. (c) 2010 Elsevier Ltd. All rights reserved.

  18. Immunogenicity of a modified-live virus vaccine against bovine viral diarrhea virus types 1 and 2, infectious bovine rhinotracheitis virus, bovine parainfluenza-3 virus, and bovine respiratory syncytial virus when administered intranasally in young calves.

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    Xue, Wenzhi; Ellis, John; Mattick, Debra; Smith, Linda; Brady, Ryan; Trigo, Emilio

    2010-05-14

    The immunogenicity of an intranasally-administered modified-live virus (MLV) vaccine in 3-8 day old calves was evaluated against bovine viral diarrhea virus (BVDV) types 1 and 2, infectious bovine rhinotracheitis (IBR) virus, parainfluenza-3 (PI-3) virus and bovine respiratory syncytial virus (BRSV). Calves were intranasally vaccinated with a single dose of a multivalent MLV vaccine and were challenged with one of the respective viruses three to four weeks post-vaccination in five separate studies. There was significant sparing of diseases in calves intranasally vaccinated with the MLV vaccine, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding, greater white blood cell and platelet counts, and less severe pulmonary lesions than control animals. This was the first MLV combination vaccine to demonstrate efficacy against BVDV types 1 and 2, IBR, PI-3 and BRSV in calves 3-8 days of age. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines.

    Science.gov (United States)

    Gasper, David J; Neldner, Brandon; Plisch, Erin H; Rustom, Hani; Carrow, Emily; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M

    2016-12-01

    CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the

  20. Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines.

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    David J Gasper

    2016-12-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTLs are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory

  1. Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

    Science.gov (United States)

    Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-12-01

    H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  2. Intranasal vaccination of dogs with liver avirulent Bordetella bronchiseptica: correlation of serum agglutination titer and the formation of secretory IgA with protection against experimentally induced infectious tracheobronchitis.

    Science.gov (United States)

    Bey, R F; Shade, F J; Goodnow, R A; Johnson, R C

    1981-07-01

    Dogs inoculated intranasally with a live avirulent Bordetella bronchiseptica vaccine were monitored for the development of resistance to experimentally induced infectious tracheobronchitis (canine cough). Dogs were challenge exposed with a virulent strains of B bronchiseptica at various times after they were vaccinated. Clinical protection was detectable as early as 48 hours. At postvaccination days 4, 5, and 14, 56%, 83%, and 95% protection was observed. Humoral immunoglobulin (Ig) titers ranged from 1:8.6 on day 0 to 1:147 on postvaccination day 21. In the monitoring of B bronchiseptica-specific secretory IgA by indirect immunofluorescence, titers appeared as early as day 4 after vaccination. The IgA titers ranged from 1:16 on day 4 to 1: 1,024 on day 21. The appearance of IgA titers correlated with the development of resistance to clinical infection.

  3. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

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    Kristin Brekke

    Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

  4. Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity.

    Science.gov (United States)

    Bissa, Massimiliano; Quaglino, Elena; Zanotto, Carlo; Illiano, Elena; Rolih, Valeria; Pacchioni, Sole; Cavallo, Federica; De Giuli Morghen, Carlo; Radaelli, Antonia

    2016-10-01

    The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Considering the closely related animal poxviruses that also arise as zoonoses, and the increasing number of unvaccinated or immunocompromised people, a safer and more effective vaccine is still required. With this aim, new vectors based on avian poxviruses that cannot replicate in mammals should improve the safety of conventional vaccines, and protect from zoonotic orthopoxvirus diseases, such as cowpox and monkeypox. In this study, DNA and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VV IHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27 antibodies and IFNγ-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VV IHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/intranasal administration routes contributed to effective immune responses and mouse survival. Copyright

  5. Use of a Guinea pig-specific transcriptome array for evaluation of protective immunity against genital chlamydial infection following intranasal vaccination in Guinea pigs.

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    Wali, Shradha; Gupta, Rishein; Veselenak, Ronald L; Li, Yansong; Yu, Jieh-Juen; Murthy, Ashlesh K; Cap, Andrew P; Guentzel, M Neal; Chambers, James P; Zhong, Guangming; Rank, Roger G; Pyles, Richard B; Arulanandam, Bernard P

    2014-01-01

    Guinea pigs have been used as a second animal model to validate putative anti-chlamydial vaccine candidates tested in mice. However, the lack of guinea pig-specific reagents has limited the utility of this animal model in Chlamydia sp. vaccine studies. Using a novel guinea pig-specific transcriptome array, we determined correlates of protection in guinea pigs vaccinated with Chlamydia caviae (C. caviae) via the intranasal route, previously reported by us and others to provide robust antigen specific immunity against subsequent intravaginal challenge. C. caviae vaccinated guinea pigs resolved genital infection by day 3 post challenge. In contrast, mock vaccinated animals continued to shed viable Chlamydia up to day 18 post challenge. Importantly, at day 80 post challenge, vaccinated guinea pigs experienced significantly reduced genital pathology - a sequelae of genital chlamydial infections, in comparison to mock vaccinated guinea pigs. Sera from vaccinated guinea pigs displayed antigen specific IgG responses and increased IgG1 and IgG2 titers capable of neutralizing GPIC in vitro. Th1-cellular/inflammatory immune genes and Th2-humoral associated genes were also found to be elevated in vaccinated guinea pigs at day 3 post-challenge and correlated with early clearance of the bacterium. Overall, this study provides the first evidence of guinea pig-specific genes involved in anti-chlamydial vaccination and illustrates the enhancement of the utility of this animal model in chlamydial pathogenesis.

  6. Peripheral expression of LACK-mRNA induced by intranasal vaccination with PCI-NEO-LACK defines the protection duration against murine visceral leishmaniasis.

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    De Oliveira Gomes, Daniel Cláudio; Schwedersky, Rodrigo Porto; Barbosa De-Melo, Luiz Dione; Da Silva Costa Souza, Beatriz Lilian; De Matos Guedes, Herbert Leonel; Lopes, Ulisses Gazos; Rossi-Bergmann, Bartira

    2012-10-01

    LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in the protozoan of the genus Leishmania, which is associated with the immunopathogenesis and susceptibility of BALB/c mice to Leishmania major infection. We previously demonstrated that intranasal immunization with a plasmid DNA encoding the p36/LACK leishmanial antigen (pCI-neo-LACK) followed by challenge 7 days after a booster dose effectively protects BALB/c mice against both cutaneous and visceral leishmaniasis. In the present study, the correlation between systemic mRNA expression after nasal DNA uptake, and the duration of protective immunity was addressed. LACK mRNA transcripts were detected in the spleen, brain, cervical lymph nodes and popliteal lymph nodes as early as 7 days, lasting 3 months after vaccination with pCI-neo-LACK. The kinetics of transcript expression correlated with enhanced cutaneous hypersensitivity against parasite antigens. Leishmania chagasi infection at 7 days or 3 months, but not 6 months after vaccination resulted in significantly lower parasite loads as compared with non-vaccinated controls. Protection also correlated with enhanced spleen cell responsiveness to parasite antigens leading to increased IFN- γ and IL-4 and decreased IL-10 production. Together, these data demonstrate that the protection conferred by the intranasal DNA vaccine lasts at least 3 months and is associated with expression of vaccine mRNA in peripheral organs.

  7. Concurrent administration of an intranasal vaccine containing feline herpesvirus-1 (FHV-1) with a parenteral vaccine containing FHV-1 is superior to parenteral vaccination alone in an acute FHV-1 challenge model.

    Science.gov (United States)

    Reagan, K L; Hawley, J R; Lappin, M R

    2014-08-01

    The administration of intranasal (IN) or subcutaneous (SC) vaccines containing modified live feline herpesvirus 1 (FHV-1) offers some level of protection against FHV-1 challenge, but relative efficacy is vaccinated concurrently with IN and SC vaccines containing FHV-1 (Group 1, n = 8); (2) kittens vaccinated with a SC FHV-1 vaccine alone (Group 2, n = 8), and (3) unvaccinated control kittens (Group 3, n = 8). All kittens were FHV-1 naïve at enrolment, and challenge with a virulent strain of FHV-1 was performed 1 week after vaccination. Daily clinical signs and pharyngeal FHV-1 shedding were recorded over a 21-day infection period. Overall, kittens in Group 1 had significantly less severe clinical illness than those in Group 2 (P vaccines was superior to administration of the SC FHV-1 vaccine alone in this challenge model of FHV-1 naïve kittens. Copyright © 2014. Published by Elsevier Ltd.

  8. Canine infectious tracheobronchitis: effects of an intranasal live canine parainfluenza-Bordetella bronchiseptica vaccine on viral shedding and clinical tracheobronchitis (kennel cough).

    Science.gov (United States)

    Kontor, E J; Wegrzyn, R J; Goodnow, R A

    1981-10-01

    A modified-live intranasal (IN) canine parainfluenza (CPI)-virus Bordetella bronchiseptica vaccine was evaluated in dogs for efficacy against laboratory-induced canine infectious tracheobronchitis. The comparative efficacies of IN and parenteral administrations of the CPI virus fraction were also evaluated. The frequency and duration of clinical tracheobronchitis, blood serum agglutination titer, humoral antibody response, and duration of CPI virus and B bronchiseptica shedding were measured. Group A dogs were vaccinated subcutaneously or IM with an experimental CPI vaccine and challenge exposed with CPI virus. Group B dogs were vaccinated IN with avirulent CPI virus-B bronchiseptica live antigens and challenge exposed with virulent CPI virus and virulent B bronchiseptica. The IN vaccination (group B) significantly reduced (P less than or equal to 0.001) the occurrence of clinical tracheobronchitis by 96%. The combined challenge exposure of virulent CPI and virulent B bronchiseptica produced a synergistic enhancement of the clinical signs of kennel cough. The percentage of days after challenge exposure that virus shedding was detected for controls equaled 70% as compared with 50% and only 1% for parenterally and IN vaccinated dogs, respectively. Isolation of virulent B bronchiseptica microorganisms was reduced 89% in dogs vaccinated IN compared to controls. The geometric mean humoral antibody titers to CPI virus after 2 parenteral vaccinations and 1 IN vaccination were 1:43 and 1:34, respectively.

  9. Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.

    Science.gov (United States)

    Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L

    2013-11-01

    We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination. © 2013 Elsevier Inc. All rights reserved.

  10. Development and evaluation of chitosan microspheres for tetanus, diphtheria and divalent vaccines: a comparative study of subcutaneous and intranasal administration in mice.

    Science.gov (United States)

    Hashem, Fahima M; Fahmy, Sahar A; El-Sayed, Aly M; Al-Sawahli, Majid M

    2013-01-01

    There is a need to use the new technologies to induce immunity with minimum number of vaccination sessions to ensure compliance with reducing cost. To develop single shot vaccines of tetanus, diphtheria and divalent toxoids microsphere's formulations and to induce their immune response after intranasal and subcutaneous administration in mice. The microspheres were prepared using different concentrations of chitosan. Microsphere's morphology, particle size analysis, encapsulation efficiency and antigen integrity were performed and the best formulations were selected for in vitro and in vivo testing in mice. The developed microspheres have a yield percent of 70.3-91.5%. In vitro release of antigens indicated that tetanus release was increased up to 75 and 81% post T5 and TD5 formulations respectively, whereas diphtheria cumulative release increased up to 74 and 69% post D3 and TD5, respectively. Antibody levels produced were lower than that obtained from alum adsorbed vaccine but higher than the minimum level required to induce immunogenicity (>0.01 IU/mL). The subcutaneous route of administration was superior over the intranasal route in producing higher antibody levels. Chitosan microspheres were developed successfully and prove that chitosan represents a good candidate for vaccines delivery.

  11. Vaccination of children with a live-attenuated, intranasal influenza vaccine – analysis and evaluation through a Health Technology Assessment

    Directory of Open Access Journals (Sweden)

    Andersohn, Frank

    2014-10-01

    Full Text Available [english] Background: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the (STIKO as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view.Method: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++, if they met the criteria of Results: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction – RRR – of laboratory confirmed influenza infection approx. 80% and 50%, respectively. In children aged >7 to 17 years (= 18th year of their lives, LAIV is superior to a vaccination with TIV (RRR 32%. For this age group, no

  12. Intranasally administered Endocine formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets.

    Science.gov (United States)

    Maltais, Anna-Karin; Stittelaar, Koert J; Veldhuis Kroeze, Edwin J B; van Amerongen, Geert; Dijkshoorn, Marcel L; Krestin, Gabriel P; Hinkula, Jorma; Arwidsson, Hans; Lindberg, Alf; Osterhaus, Albert D M E

    2014-05-30

    Influenza is a contagious respiratory disease caused by an influenza virus. Due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. This allows annual vaccination with multivalent seasonal influenza vaccines, recommended especially for high-risk groups. There is a need for a seasonal influenza vaccine that induces broader and longer lasting protection upon easy administration. Endocine is a lipid-based mucosal adjuvant composed of endogenous lipids found ubiquitously in the human body. Intranasal administration of influenza antigens mixed with this adjuvant has been shown to induce local and systemic immunity as well as protective efficacy against homologous influenza virus challenge in mice. Here we used ferrets, an established animal model for human influenza virus infections, to further investigate the potential of Endocine as an adjuvant. Intranasal administration of inactivated pandemic H1N1/California/2009 split antigen or whole virus antigen mixed with Endocine induced high levels of serum hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers that were also cross reactive against distant swine viruses of the same subtype. HI and VN antibody titers were already demonstrated after a single nasal immunization. Upon intratracheal challenge with a homologous challenge virus (influenza virus H1N1/The Netherlands/602/2009) immunized ferrets were fully protected from virus replication in the lungs and largely protected against body weight loss, virus replication in the upper respiratory tract and pathological changes in the respiratory tract. Endocine formulated vaccines containing split antigen induced higher HI and VN antibody responses and better protection from body weight loss and virus shedding in the upper respiratory tract than the Endocine formulated vaccine containing whole virus antigen. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All

  13. Clinical protection against caprine herpesvirus 1 genital infection by intranasal administration of a live attenuated glycoprotein E negative bovine herpesvirus 1 vaccine

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    Meurens François

    2007-12-01

    Full Text Available Abstract Background Caprine herpesvirus 1 (CpHV-1 is responsible of systemic diseases in kids and genital diseases leading to abortions in goats. CpHV-1 is widespread and especially in Mediterranean countries as Greece, Italy and Spain. CpHV-1 is antigenically and genetically closely related to bovine herpesvirus 1 (BoHV-1. Taking into account the biological properties shared by these two viruses, we decided in the current study to assess the protection of a live attenuated glycoprotein E (gE negative BoHV-1 vaccine against a genital CpHV-1 infection in goats. Results The vaccine was inoculated intranasally twice three weeks apart followed by a subsequent CpHV-1 intravaginal challenge which is the natural route of infection in three goats. To analyse the safety and the efficacy of this marker vaccine, two groups of three goats served as controls: one immunised with a virulent CpHV-1 and one uninoculated until the challenge. Goats were clinically monitored and all sampling procedures were carried out in a blind manner. The vaccine did not induce any undesirable local or systemic reaction and goats did not excrete gE-negative BoHV-1. After challenge, a significant reduction in disease severity was observed in immunised goats. Moreover, goats immunised with either gE-negative BoHV-1 or CpHV-1 exhibited a significant reduction in the length and the peak of viral excretion. Antibodies neutralising both BoHV-1 and CpHV-1 were raised in immunised goats. Conclusion Intranasal application of a live attenuated gE-negative BoHV-1 vaccine is able to afford a clinical protection and a reduction of virus excretion in goats challenged by a CpHV-1 genital infection.

  14. Comparison of interferon and bovine herpesvirus-1-specific IgA levels in nasal secretions of dairy cattle administered an intranasal modified live viral vaccine prior to calving or on the day of calving.

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    Cortese, Victor S; Woolums, Amelia; Hurley, David J; Berghaus, Roy; Bernard, John K; Short, Thomas H

    2017-05-01

    Thirty-two Holstein cows were allocated to receive intranasal vaccination with modified live bovine herpesvirus-1 (BHV-1), bovine respiratory syncytial virus (BRSV) and parainfluenza type 3 virus (PI3V) vaccine either two weeks prior to their projected calving date, or within 24h after calving. Nasal secretions were collected twice at a 12-h interval on the day prior to vaccination (day 0) and at 2, 4, 7, 10 and 14days post vaccination to measure interferon (IFN) alpha, IFN-beta, IFN-gamma, and BHV-1-specific IgA by ELISA. Serum neutralizing antibody titers to BHV-1 and BRSV were measured on days 0, 7, and 14. There was a significant treatment effect (p<0.0004) and interaction (p<0.05) on nasal BHV-1 IgA levels, with higher IgA levels in cows vaccinated within 24h after calving. There was a significant treatment effect on nasal IFN-gamma concentration (p<0.05) and on nasal total IFN concentration (p<0.05), with higher IFN-gamma and total IFN concentrations seen in cows vaccinated within 24h after calving. There was no significant treatment or interaction effect on nasal IFN-alpha or IFN-beta concentrations, or on serum neutralizing titers to BRSV. In spite of prior viral vaccination during the previous lactation, cows vaccinated on the day of calving responded to an intranasal viral vaccination with increased concentrations of IFN-gamma and increased titers of IgA following vaccination which was significantly higher than cows vaccinated precalving. This study is the first to examine respiratory mucosal responses in immunologically mature dairy cattle vaccinated intranasally before and after calving. Copyright © 2017. Published by Elsevier B.V.

  15. Enhancement of Intranasal Vaccination in Mice with Deglycosylated Chain A Ricin by LTR72, a Novel Mucosal Adjuvant

    Science.gov (United States)

    2006-03-15

    in developing and applying adjuvants that can enhance mucosal immunity. Parenteral administration of aluminum (alum) hydroxide or phosphate (the... intramuscular immunization. Infect Immun 1999;67:4276–9. [16] O’Hagen DT, Rappuoli R. Novel delivery systems for intranasal immunization with inactivated

  16. Efficacy of an intranasal modified live bovine respiratory syncytial virus and temperature-sensitive parainfluenza type 3 virus vaccine in 3-week-old calves experimentally challenged with PI3V.

    Science.gov (United States)

    Vangeel, Ilse; Ioannou, Faye; Riegler, Lutz; Salt, Jeremy S; Harmeyer, Silke S

    2009-01-01

    Two experimental parainfluenza type 3 virus (PI3V) challenge studies were undertaken to evaluate the efficacy of a single intranasal dose of an attenuated live vaccine containing modified live bovine respiratory syncytial virus (BRSV) and temperature-sensitive PI3V in 3-week-old calves. In the first study, vaccine efficacy was evaluated in colostrum deprived calves. Nasal shedding of PI3V was highly significantly reduced in vaccinated calves challenged 10 days or 21 days after vaccination. In the second study, vaccine efficacy was assessed in calves with maternal antibodies against PI3V by challenge 66 days post-vaccination. Vaccination also significantly reduced PI3V excretion after challenge in this study. In both studies, clinical signs after challenge were very mild and were not different between vaccinated and control calves.

  17. A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.

    Science.gov (United States)

    Jiao, Yue-Ying; Fu, Yuan-Hui; Yan, Yi-Fei; Hua, Ying; Ma, Yao; Zhang, Xiu-Juan; Song, Jing-Dong; Peng, Xiang-Lei; Huang, Jiaqiang; Hong, Tao; He, Jin-Sheng

    2017-08-01

    Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully. The resulting VLPs showed similar immunoreactivity and function to RSV virion in vitro. Moreover, Th1 polarized response, and effective mucosal virus-neutralizing antibody and CD8 + T-cell responses were induced by a single intranasal (i.n.) administration of RSV VLPs rather than intramuscular (i.m.) inoculation, although the comparable RSV F-specific serum IgG and long-lasting RSV-specific neutralizing antibody were detected in the mice immunized by both routes. Upon RSV challenge, VLP-immunized mice showed increased viral clearance but decreased signs of enhanced lung pathology and fewer eosinophils compared to mice immunized with formalin-inactivated RSV (FI-RSV). In addition, a single i.n. RSV VLP vaccine has the capability to induce RSV-specific long-lasting neutralizing antibody responses observable up to 15 months. Our results demonstrate that the long-term and memory immune responses in mice against RSV were induced by a single i.n. administration of RSV VLP vaccine, suggesting a successful approach of RSV VLPs as an effective and safe mucosal vaccine against RSV infection, and an applicable and qualified platform of FGAd-infected Vero cells for VLP production. Copyright © 2017. Published by Elsevier B.V.

  18. Fc Receptor-Targeting of Immunogen as a Strategy for Enhanced Antigen Loading, Vaccination, and Protection Using Intranasally-Administered Antigen-Pulsed Dendritic Cells

    Science.gov (United States)

    Pham, Giang H.; Iglesias, Bibiana V.; Gosselin, Edmund J.

    2014-01-01

    Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naïve T cells. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Studies have also demonstrated that targeting Ags to Fcγ receptors (FcγR) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo. Specifically, our studies using an F. tularensis (Ft) infectious disease vaccine model have demonstrated that targeting immunogens to FcγR via intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft (iFt) immune complexes (ICs) enhances protection against Ft challenge. Ft is the causative agent of tularemia, a debilitating disease of humans and other mammals and a category A biothreat agent for which there is no approved vaccine. Therefore, using iFt Ag as a model immunogen, we sought to determine if ex vivo targeting of iFt to FcγR on DCs would enhance the potency of i.n. administered iFt-pulsed DCs. In this study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with iFt or mAb-iFt ICs. Intranasal administration of mAb-iFt-pulsed BMDCs enhanced humoral and cellular immune responses, as well as protection against Ft live vaccine strain (LVS) challenge. Increased protection correlated with increased iFt loading on the BMDC surface as a consequence of FcγR targeting. However, the inhibitory FcγRIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo to FcγR on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag required, while also avoiding the inhibitory impact of FcγRIIB. Thus, this represents a simple and less invasive strategy for increasing the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and cancer. PMID:25068496

  19. Intranasal vaccination with a secreted chlamydial protein enhances resolution of genital Chlamydia muridarum infection, protects against oviduct pathology, and is highly dependent upon endogenous gamma interferon production.

    Science.gov (United States)

    Murthy, Ashlesh K; Chambers, James P; Meier, Patricia A; Zhong, Guangming; Arulanandam, Bernard P

    2007-02-01

    There is currently no licensed vaccine against Chlamydia trachomatis, the leading cause of sexually transmitted bacterial disease worldwide. Conventional vaccination attempts using surface-exposed chlamydial antigens have achieved only partial success. We have employed a novel vaccination strategy using a secreted protein, chlamydial protease-like activity factor (CPAF), which has been shown to degrade host major histocompatibility complex transcription factors and keratin-8 and therefore may allow immune evasion and establishment of a productive infection. Intranasal immunization using recombinant CPAF (rCPAF) plus interleukin-12 (IL-12) (rCPAF+IL-12 immunization) was used to assess the protective immunity against genital Chlamydia muridarum infection in BALB/c mice. rCPAF+IL-12 immunization induced robust gamma interferon (IFN-gamma) production and minimal IL-4 production by splenocytes upon in vitro recall with rCPAF. The total and immunoglobulin G2a (IgG2a) anti-rCPAF antibody levels in serum were significantly elevated after rCPAF+IL-12 vaccination, as were the total antibody, IgG2a, and IgA levels in bronchoalveolar lavage and vaginal fluids when the animals were compared to animals that received rCPAF alone. rCPAF+IL-12-vaccinated mice displayed significantly reduced bacterial shedding upon chlamydial challenge and accelerated resolution of infection compared to mock-immunized (phosphate-buffered saline) animals. Moreover, rCPAF+IL-12-immunized animals exhibited protection against pathological consequences of chlamydial infection, including the development of hydrosalpinx and oviduct dilatation. This vaccination regimen also reduced the development of fibrosis and the influx of neutrophils into the upper genital tract when the animals were compared to mock-immunized (phosphate-buffered saline) animals after bacterial challenge. rCPAF+IL-12-mediated resolution of the bacterial infection and protection against Chlamydia-induced inflammatory disease were highly

  20. An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine.

    Science.gov (United States)

    Alejo, Diana M; Moraes, Mauro P; Liao, Xiaofen; Dias, Camila C; Tulman, Edan R; Diaz-San Segundo, Fayna; Rood, Debra; Grubman, Marvin J; Silbart, Lawrence K

    2013-04-26

    Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help prevent initial infection and viral spread. E. coli heat-labile enterotoxin (LT) has been described as one of the few molecules that have adjuvant activity at mucosal surfaces. The objective of this study was to evaluate the efficacy of replication-defective adenovirus 5 (Ad5) vectors encoding either of two LT-based mucosal adjuvants, LTB or LTR72. These vectored adjuvants were delivered intranasally to mice concurrent with an Ad5-FMDV vaccine (Ad5-A24) to assess their ability to augment mucosal and systemic humoral immune responses to Ad5-A24 and protection against FMDV. Mice receiving Ad5-A24 plus Ad5-LTR72 had higher levels of mucosal and systemic neutralizing antibodies than those receiving Ad5-A24 alone or Ad5-A24 plus Ad5-LTB. The vaccine plus Ad5-LTR72 group also demonstrated 100% survival after intradermal challenge with a lethal dose of homologous FMDV serotype A24. These results suggest that Ad5-LTR72 could be used as an important tool to enhance mucosal and systemic immunity against FMDV and potentially other pathogens with a common route of entry. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    Full Text Available INTRODUCTION: RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2 ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine. OBJECTIVE: To explore if intranasal (IN immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity. METHODS: We produced RSV-virosomes carrying TLR2 (Pam3CSK4 and/or NOD2 (L18-MDP ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice. RESULTS: Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced

  2. Effect of ambient temperature on viral replication and serum antibody titers following administration of a commercial intranasal modified-live infectious bovine rhinotracheitis-parainfluenza-3 virus vaccine to beef cattle housed in high- and moderate-ambient temperature environments.

    Science.gov (United States)

    Grissett, Gretchen P; White, Brad J; Anderson, David E; Larson, Robert E; Miesner, Matt D

    2014-12-01

    To evaluate the effect of ambient temperature on viral replication and serum antibody titers following administration of an intranasal modified-live infectious bovine rhinotracheitis (IBR)-parainfluenza-3 (PI3) virus vaccine to beef calves housed in high- (> 32°C) and moderate- (21°C) ambient temperature environments. 28 calves (mean weight, 206.8 kg). Calves were randomly allocated to 4 treatment groups (housed outdoors during high ambient temperature with [HAT; n = 10] or without [HAC; 4] vaccination or housed indoors in a moderate ambient temperature with [MAT; 10] or without [MAC; 4] vaccination). Rectal and nasal mucosal temperatures were recorded every 2 hours from 8 AM to 8 PM on days 0 (vaccination) and 1. Nasal swab specimens were obtained on days 0 through 7 for virus isolation. Serum samples were collected on days 0, 7, 14, and 28 for determination of antibody titers. Mean rectal temperature did not differ among the treatment groups. Mean nasal temperature for the HAT group was significantly higher than that for the MAT group at 6, 24, 30, 32, and 38 hours after vaccination. Viable IBR virus was isolated from all vaccinated calves on days 1 through 6. Two weeks after vaccination, vaccinated calves had anti-IBR antibody titers that were significantly greater than those for unvaccinated calves. Mean anti-IBR antibody titers did not differ significantly between the HAT and MAT groups. Results indicated that, following vaccination with an intranasal modified-live IBR-PI3 virus vaccine, IBR viral replication and serum antibody titers did not differ significantly between calves housed in high- and moderate-ambient temperature environments.

  3. Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

    Science.gov (United States)

    Gerlier, L; Lamotte, M; Grenèche, S; Lenne, X; Carrat, F; Weil-Olivier, C; Damm, O; Schwehm, M; Eichner, M

    2017-04-01

    We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0 ) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with

  4. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus–Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L.; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S.; Cox, Josephine H.

    2017-01-01

    Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35–vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH). Results. All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot–determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic. Conclusions. SeV-Gag primed functional, durable HIV-specific T

  5. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens.

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S; Cox, Josephine H

    2017-01-01

     We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (S L A); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (S H A); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (AS H ); and priming and boosting with a higher-dose SeV-Gag given intranasally (S H S H ).  All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (S L A and S H A) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8 + T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the S L A and S H A groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the AS H group. In contrast, the highest Gag-specific antibody titers were seen in the AS H group. Mucosal antibody responses were sporadic.  SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody

  6. Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis: effect of instillation volume and form of anesthesia.

    Directory of Open Access Journals (Sweden)

    Mark A Miller

    Full Text Available Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane vs. parenteral (ketamine/xylazine anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

  7. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low...

  8. Antibody Responses to Trivalent Inactivated Influenza Vaccine in Health Care Personnel Previously Vaccinated and Vaccinated for The First Time

    OpenAIRE

    Kuan-Ying A. Huang; Shih-Cheng Chang; Yhu-Chering Huang; Cheng-Hsun Chiu; Tzou-Yien Lin

    2017-01-01

    Inactivated influenza vaccination induces a hemagglutinin-specific antibody response to the strain used for immunization. Annual vaccination is strongly recommended for health care personnel. However, it is debatable if repeated vaccination would affect the antibody response to inactivated influenza vaccine through the time. We enrolled health care personnel who had repeated and first trivalent inactivated influenza vaccination in 2005?2008. Serological antibody responses were measured by hem...

  9. The effects of the time of intranasal splinting on bacterial colonization, postoperative complications, and patient discomfort after septoplasty operations.

    Science.gov (United States)

    Karatas, Abdullah; Pehlivanoglu, Filiz; Salviz, Mehti; Kuvat, Nuray; Cebi, Isil Taylan; Dikmen, Burak; Sengoz, Gonul

    The main reason for nasal tampon placement after septoplasty is to prevent postoperative hemorrhage, while the secondary purpose is internal stabilization after operations involving the cartilaginous-bony skeleton of the nose. Silicone intranasal splints are as successful as other materials in controlling postoperative hemorrhages of septal origin. The possibility of leaving the splints intranasally for extended periods helps stabilize the septum in the midline. However, there is nothing in the literature about how long these splints can be retained inside the nasal cavity without increasing the risk of infection, postoperative complications, and patient discomfort. The current study aimed to evaluate the association between the duration of intranasal splinting and bacterial colonization, postoperative complications, and patient discomfort. Patients who had undergone septoplasty were divided into three groups according to the day of removal of the silicone splints. The splints were removed on the fifth, seventh, and tenth postoperative days. The removed splints were microbiologically cultured. Early and late complications were assessed, including local and systemic infections, tissue necrosis, granuloma formation, mucosal crusting, synechia, and septal perforation. Postoperative patient discomfort was evaluated by scoring the levels of pain and nasal obstruction. No significant difference was found in the rate of bacterial colonization among the different groups. Decreased mucosal crusting and synechia were detected with longer usage intervals of intranasal silicone splints. Postoperative pain and nasal obstruction were also diminished by the third postoperative day. Silicone splints were well tolerated by the patients and any negative effects on postoperative patient comfort were limited. In fact, prolonged splint usage intervals reduced late complications. Long-term silicone nasal splint usage is a reliable, effective, and comfortable method in patients with

  10. The effects of the time of intranasal splinting on bacterial colonization, postoperative complications, and patient discomfort after septoplasty operations

    Directory of Open Access Journals (Sweden)

    Abdullah Karatas

    Full Text Available Abstract Introduction: The main reason for nasal tampon placement after septoplasty is to prevent postoperative hemorrhage, while the secondary purpose is internal stabilization after operations involving the cartilaginous-bony skeleton of the nose. Silicone intranasal splints are as successful as other materials in controlling postoperative hemorrhages of septal origin. The possibility of leaving the splints intranasally for extended periods helps stabilize the septum in the midline. However, there is nothing in the literature about how long these splints can be retained inside the nasal cavity without increasing the risk of infection, postoperative complications, and patient discomfort. Objective: The current study aimed to evaluate the association between the duration of intranasal splinting and bacterial colonization, postoperative complications, and patient discomfort. Methods: Patients who had undergone septoplasty were divided into three groups according to the day of removal of the silicone splints. The splints were removed on the fifth, seventh, and tenth postoperative days. The removed splints were microbiologically cultured. Early and late complications were assessed, including local and systemic infections, tissue necrosis, granuloma formation, mucosal crusting, synechia, and septal perforation. Postoperative patient discomfort was evaluated by scoring the levels of pain and nasal obstruction. Results: No significant difference was found in the rate of bacterial colonization among the different groups. Decreased mucosal crusting and synechia were detected with longer usage intervals of intranasal silicone splints. Postoperative pain and nasal obstruction were also diminished by the third postoperative day. Conclusions: Silicone splints were well tolerated by the patients and any negative effects on postoperative patient comfort were limited. In fact, prolonged splint usage intervals reduced late complications. Long-term silicone

  11. Intranasal sedatives in pediatric dentistry.

    Science.gov (United States)

    AlSarheed, Maha A

    2016-09-01

    To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol, and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry.  Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its' onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Intranasal midazolam, ketamine, and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine, and sufentanil have proven to be effective premedications.

  12. Intranasal sedatives in pediatric dentistry

    Science.gov (United States)

    AlSarheed, Maha A.

    2016-01-01

    Objectives: To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. Methods: A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry. Results: Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its’ onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Conclusion: Intranasal midazolam, ketamine and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine and sufentanil have proven to be effective premedications. PMID:27570849

  13. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    NARCIS (Netherlands)

    Verheul, R.J.

    2010-01-01

    Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need

  14. Welfare, maternal work, and on-time childhood vaccination rates.

    Science.gov (United States)

    Sohn, Min-Woong; Yoo, Joan; Oh, Elissa H; Amsden, Laura B; Holl, Jane L

    2011-12-01

    To examine effects of Temporary Assistance for Needy Families welfare cash assistance and maternal work requirements on "on-time" childhood vaccination rates. A stratified random sample of Illinois children from low-income families affected by welfare reform was monitored from 1997 to 2004. Medical records from pediatricians' offices and Medicaid claims data were used to identify the timeliness of 18 recommended vaccinations. Random-intercept logistic models were used to estimate on-time vaccine administration as a function of welfare receipt and maternal work with adjustment for characteristics of the children and mothers and time-varying covariates pertaining to the administration window for each recommended vaccine dose. Of all recommended vaccinations, 55.9% were administered on time. On-time vaccination rates were higher when families were receiving welfare than not (57.4% vs 52.8%). Children in families that either were receiving welfare or had working mothers were 1.7 to 2.1 times more likely to receive vaccinations on time compared with children in families that were not receiving welfare and did not have working mothers. When vaccine doses were stratified according to welfare status, maternal work was associated with decreased on-time vaccination rates (odds ratio: 0.73 [95% confidence interval: 0.59-0.90]) when families received welfare but increased on-time vaccination rates (odds ratio: 1.68 [95% confidence interval: 1.27-2.22]) when they did not receive welfare. These results indicate that maternal work requirements of Temporary Assistance for Needy Families had negative effects on timely administration of childhood vaccinations, although receipt of welfare itself was associated with increased on-time rates.

  15. Phase-I study MEDI-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children.

    Science.gov (United States)

    Gomez, Margarita; Mufson, Maurice A; Dubovsky, Filip; Knightly, Conor; Zeng, Wen; Losonsky, Genevieve

    2009-07-01

    A live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine was evaluated in healthy respiratory syncytial virus/parainfluenza virus type 3 seropositive children aged 1 to 9 years. Three cohorts of 40 children were randomized 1:1 to receive 10, 10, or 10 median tissue culture infectious dose50 MEDI-534 vaccine or placebo. The vaccine's safety profile was similar to placebo, no viral shedding was detected, and the vaccine was minimally immunogenic.

  16. Oral fluids as a live-animal sample for evaluating cross-reactivity and cross-protection following intranasal influenza A virus vaccination in pigs

    Science.gov (United States)

    In North American swine there are numerous antigenically distinct influenza A virus (IAV) H1 subtypes currently circulating, making vaccine development difficult due to the inability to formulate a vaccine that provides broad cross-protection. Live-attenuated influenza virus (LAIV) vaccines provide ...

  17. Intranasally administered Endocine™ formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets

    NARCIS (Netherlands)

    A.-K. Maltais (Anna-Karin); K.J. Stittelaar (Koert); E.J.B. Veldhuis Kroeze (Edwin); G. van Amerongen (Geert); M.L. Dijkshoorn (Marcel); G.P. Krestin (Gabriel); J. Hinkula (Jorma); H. Arwidsson (Hans); A. Lindberg (Alf); A.D.M.E. Osterhaus (Albert)

    2014-01-01

    textabstractInfluenza is a contagious respiratory disease caused by an influenza virus. Due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. This allows annual vaccination with multivalent seasonal influenza vaccines,

  18. Intranasal Vaccination with a Secreted Chlamydial Protein Enhances Resolution of Genital Chlamydia muridarum Infection, Protects against Oviduct Pathology, and Is Highly Dependent upon Endogenous Gamma Interferon Production▿

    OpenAIRE

    Murthy, Ashlesh K.; Chambers, James P.; Meier, Patricia A.; Zhong, Guangming; Arulanandam, Bernard P.

    2006-01-01

    There is currently no licensed vaccine against Chlamydia trachomatis, the leading cause of sexually transmitted bacterial disease worldwide. Conventional vaccination attempts using surface-exposed chlamydial antigens have achieved only partial success. We have employed a novel vaccination strategy using a secreted protein, chlamydial protease-like activity factor (CPAF), which has been shown to degrade host major histocompatibility complex transcription factors and keratin-8 and therefore may...

  19. Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV(mac251).

    Science.gov (United States)

    Zhou, Qifeng; Hidajat, Rachmat; Peng, Bo; Venzon, David; Aldrich, M Kristine; Richardson, Ersell; Lee, Eun Mi; Kalyanaraman, V S; Grimes, George; Gómez-Román, V Raúl; Summers, L Ebonita; Malkevich, Nina; Robert-Guroff, Marjorie

    2007-11-19

    Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIV(mac251) challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity.

  20. Research of beliefs concerning vaccination in modern times

    Directory of Open Access Journals (Sweden)

    Aggeliki Fragou

    2016-06-01

    Full Text Available Vaccinations are considered to be one of the most effective public health interventions. The rate of vaccination in developed countries is generally high. However, an increasing number of parents consider vaccines unsafe and unnecessary. The campaigns against vaccines have resulted in the decline in rates of vaccinated children and in the increase in outbreaks of preventable diseases. The time the first vaccines were discovered and implemented, it was when campaigns against them first emerged. Hesitation towards vaccination is a longstanding phenomenon which is closely linked to the socio-cultural background of populations in certain regions around the world. Philosophical or religious beliefs are one of the strongest arguments for refusing, even mandatory, vaccinations. Additionally, suspicion and concern about immunization is quite common. Internationally, in parts of Asia and Africa, the distrust of vaccines is associated sometimes with conspiracy theories. Health professionals play a central role in maintaining public confidence in immunization, a role which is becoming more and more difficult nowadays, since immunization programs have become more complex. Health professionals’ attitude of understanding and acceptance of different beliefs will help to strengthen the relationship of trust between the staff and patients / parents. The efforts of health professionals should focus on providing all the necessary information to enable parents to make informed decisions.

  1. Infection-enhancing lipopeptides do not improve intranasal immunization of cotton rats with a delta-G candidate live-attenuated human respiratory syncytial virus vaccine

    NARCIS (Netherlands)

    D.T. Nguyen (Tien); J. Boes (Jolande); G. van Amerongen (Geert); Y. van Remmerden (Yvonne); S. Yüksel (Selma); T. Guichelaar (Teun); A.D.M.E. Osterhaus (Albert); R.L. de Swart (Rik)

    2013-01-01

    textabstractDevelopment of live-attenuated human respiratory syncytial virus (HRSV) vaccines has proven to be difficult. Several vaccine candidates were found to be over-attenuated and displayed limited immunogenicity. Recently, we identified three synthetic cationic lipopeptides that enhanced

  2. Intranasal vaccination with replication defective adenovirus-5 encoding influenza hemagglutinin elicits protective immunity to homologous challenge and partial protection to heterologous challenge in pigs

    Science.gov (United States)

    Influenza A virus (IAV) is widely circulating in the swine population and causes significant economic loss. To combat IAV infection the swine industry utilizes adjuvanted whole inactivated virus (WIV) vaccines. These vaccines can provide sterilizing immunity towards homologous virus but often have l...

  3. Improved coverage and timing of childhood vaccinations in two post-Soviet countries, Armenia and Kyrgyzstan

    OpenAIRE

    Schweitzer, A.; Krause, G.; Pessler, F.; Akmatov, M. K.

    2015-01-01

    Abstract Background Timing of childhood vaccinations has received close attention in many countries. Little is known about the trends in correctly timed vaccination in former Soviet countries. We examined trends in vaccination coverage and correct timing of vaccination in two post-Soviet countries, Armenia and Kyrgyzstan, and analyzed factors associated with delayed vaccinations. Met...

  4. Timing of Haemophilus influenzae type b vaccination after cardiac surgery.

    Science.gov (United States)

    Takanashi, Manabu; Ogata, Shohei; Honda, Takashi; Nomoto, Keiko; Mineo, Eri; Kitagawa, Atsushi; Ando, Hisashi; Kimura, Sumito; Nakahata, Yayoi; Oka, Norihiko; Miyaji, Kagami; Ishii, Masahiro

    2016-08-01

    The best time for vaccination in infants with congenital heart disease (CHD) after cardiopulmonary bypass (CPB) surgery is unclear, but it is important to prevent Haemophilus influenzae type b (Hib) infection in infants with CHD after CPB surgery. To identify the best time for Hib vaccination in infants with CHD after CPB surgery, we investigated the immunological status, and the efficacy and safety of Hib vaccination after CPB surgery. Sixteen subjects who underwent surgical correction of ventricular septal defect with CPB were investigated. Immunological status and cytokines were analyzed before surgery, 2 months after surgery, and before Hib booster vaccination. Hib-specific IgG was also measured to evaluate the effectiveness of vaccination. Immunological status before and 2 months after surgery (e.g. whole blood cells and lymphocyte subset profile) was within the normal range and no subjects had hypercytokinemia. Additionally, all subjects who received Hib vaccination at 2-3 months after CPB surgery had effective serum Hib-specific IgG level for protection against Hib infection without any side-effects. CPB surgery does not influence acquired immunity and Hib vaccination may be immunologically safe to perform at 2 months after CPB surgery. Hib vaccination at 2-3 months after CPB surgery was effective in achieving immunization for infants with simple left-right shunt-type CHD. © 2015 Japan Pediatric Society.

  5. Compatibility of a bivalent modified-live vaccine against Bordetella bronchiseptica and CPiV, and a trivalent modified-live vaccine against CPV, CDV and CAV-2.

    Science.gov (United States)

    Jacobs, A A C; Bergman, J G H E; Theelen, R P H; Jaspers, R; Helps, J M; Horspool, L J I; Paul, G

    2007-01-13

    Eight puppies (group 1) were vaccinated once with a bivalent modified-live vaccine against infectious tracheobronchitis by the intranasal route and at the same time with an injectable trivalent vaccine against canine parvovirus, canine distemper virus and canine adenovirus; a second group of eight puppies (group 2) was vaccinated only with the intranasal bivalent vaccine, and a further eight puppies (group 3) were vaccinated only with the injectable trivalent vaccine. Three weeks later they were all challenged with wildtype Bordetella bronchiseptica and canine parainfluenza virus by the aerosol route, and their antibody responses to the five vaccine organisms were determined. Oronasal swabs were taken regularly before and after the challenge for the isolation of bacteria and viruses, and the puppies were observed for clinical signs for three weeks after the challenge. There were no significant differences in the puppies' titres against canine parvovirus, canine distemper virus and canine adenovirus type 2 between the groups vaccinated with or without the bivalent intranasal vaccine. After the challenge the mean clinical scores of the two groups vaccinated with the intranasal vaccine were nearly 90 per cent lower (P=0.001) than the mean score of the group vaccinated with only the trivalent injectable vaccine, and the puppies in this group all became culture-positive for B bronchiseptica and canine parainfluenza virus. There were only small differences between the rates of isolation of B bronchiseptica from groups 1, 2 and 3, but significantly lower yields of canine parainfluenza virus were isolated from groups 1 and 2 than from group 3.

  6. Intramuscular delivery of adenovirus serotype 5 vector expressing humanized protective antigen induces rapid protection against anthrax that may bypass intranasally originated preexisting adenovirus immunity.

    Science.gov (United States)

    Wu, Shipo; Zhang, Zhe; Yu, Rui; Zhang, Jun; Liu, Ying; Song, Xiaohong; Yi, Shaoqiong; Liu, Ju; Chen, Jianqin; Yin, Ying; Xu, Junjie; Hou, Lihua; Chen, Wei

    2014-02-01

    Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10⁸ infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD₅₀) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

  7. Addressing Parental Vaccine Concerns: Engagement, Balance, and Timing.

    Directory of Open Access Journals (Sweden)

    Jason M Glanz

    2015-08-01

    Full Text Available The recent United States measles epidemic has sparked another contentious national discussion about childhood vaccination. A growing number of parents are expressing concerns about the safety of vaccines, often fueled by misinformation from the internet, books, and other nonmedical sources. Many of these concerned parents are choosing to refuse or delay childhood vaccines, placing their children and surrounding communities at risk for serious diseases that are nearly 100% preventable with vaccination. Between 10% and 15% of parents are asking physicians to space out the timing of vaccines, which often poses an ethical dilemma for physicians. This trend reflects a tension between personal liberty and public health, as parents fight to control the decisions that affect the health of their children and public health officials strive to maintain high immunization rates to prevent outbreaks of vaccine-preventable diseases. Interventions to address this emerging public health issue are needed. We describe a framework by which web-based interventions can be used to help parents make evidence-based decisions about childhood vaccinations.

  8. Addressing Parental Vaccine Concerns: Engagement, Balance, and Timing.

    Science.gov (United States)

    Glanz, Jason M; Kraus, Courtney R; Daley, Matthew F

    2015-08-01

    The recent United States measles epidemic has sparked another contentious national discussion about childhood vaccination. A growing number of parents are expressing concerns about the safety of vaccines, often fueled by misinformation from the internet, books, and other nonmedical sources. Many of these concerned parents are choosing to refuse or delay childhood vaccines, placing their children and surrounding communities at risk for serious diseases that are nearly 100% preventable with vaccination. Between 10% and 15% of parents are asking physicians to space out the timing of vaccines, which often poses an ethical dilemma for physicians. This trend reflects a tension between personal liberty and public health, as parents fight to control the decisions that affect the health of their children and public health officials strive to maintain high immunization rates to prevent outbreaks of vaccine-preventable diseases. Interventions to address this emerging public health issue are needed. We describe a framework by which web-based interventions can be used to help parents make evidence-based decisions about childhood vaccinations.

  9. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

    Directory of Open Access Journals (Sweden)

    Rasmus Mortensen

    Full Text Available Streptococcus pyogenes (group A streptococcus, GAS is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

  10. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

    Science.gov (United States)

    Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus; Christensen, Jan Pravsgaard; Andersen, Peter; Dietrich, Jes

    2017-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

  11. Association between timely initiation of hepatitis B vaccine and completion of the hepatitis B vaccine and national immunization program vaccine series

    Directory of Open Access Journals (Sweden)

    Jiang-nan Wu

    2016-10-01

    Conclusions: Coverage with a timely first dose of HB vaccine is high in children in the community and newborns in hospital, and timely receipt of the first dose of HB vaccine is associated with an increased likelihood of completing the HB vaccine series and the NIPV series in Fujian, China.

  12. Hepatitis B vaccination timing: results from demographic health surveys in?47 countries

    OpenAIRE

    Schweitzer, Aparna; Akmatov, Manas K; Krause, G?rard

    2017-01-01

    Abstract Objective To examine the impact of hepatitis B vaccination schedules and types of vaccines on hepatitis B vaccination timing. Methods We used data for 211?643 children from demographic and health surveys in 47 low- and middle-income countries (median study year 2012). Data were from vaccination cards and maternal interviews. We grouped countries according to the vaccination schedule and type of vaccine used (monovalent or combination). For each country, we calculated hepatitis B vacc...

  13. Preparation of ESAT-6 Nanoparticles and Evaluation of Humoral Immunity after Intranasal Administration

    Directory of Open Access Journals (Sweden)

    H Najminezhad

    2013-01-01

    Full Text Available Introduction: Among several tuberculosis vaccine candidates for replacement of BCG, ESAT-6 protein has a special role. Since mycobacterium tuberculosis infection most often attacks the lungs, intranasal rout can be regarded as appropriate methods for tuberculosis vaccines and drug delivery. One of the appropriate systems for intranasal vaccine delivery is using biodegradable nanoparticles. Among biodegradable polymers, chitosan polymer has great features to increase the response of immunity system. This study aimed to investigate the specific humoral immune response of mice model after encapsulation of recombinant ESAT-6 antigen in chitosan nanoparticles. Methods: The chitosan nanoparticles containing ESAT-6 antigen were synthesized by ionic gelation. Nanoparticle properties including morphology, particle size, zeta potential, encapsulation rates, and protein release were measured in vitro. The immunization was performed through the nose for 3 times on days 0 and 14 and 28. 2 weeks after last administration, blood samples were collected and specific IgG titers were measured by indirect ELISA. Results: The nanoparticles synthesized had appropriate properties. The mean size of resulting nanoparticles was 242.8 nm by excellent antigen loading capacity (95.23 %. The vitro release of antigen from nanoparticles after 200 hours was detected as 67.5%. The Level of IgG antibody showed significant increase in the group that had received chitosan nanoparticles containing ESAT-6 compared with other groups. Conclusion: ESAT-6 protein was encapsulated in chitosan nanoparticles successfully. Administration of chitosan nanoparticles can be a suitable method for administration of humoral immunity antigens of Mycobacterium tuberculosis through intranasal rout.

  14. Delayed vaccine virus replication in chickens vaccinated subcutaneously with an immune complex infectious bursal disease vaccine: Quantification of vaccine virus by real-time polymerase chain reaction

    OpenAIRE

    Iván, Judit; Velhner, Maja; Ursu, Krisztina; Germán, Péter; Mató, Tamás; Drén, Csaba Nick; Mészáros, János

    2005-01-01

    The distribution of the immune complex vaccine virus for infectious bursal disease (IBD) in tissue was examined and the viral loads of the organs were quantitatively compared. One-day-old specific pathogen free (SPF) and maternally immune broiler chickens were injected subcutaneously with the vaccine. Lymphoid and non-lymphoid tissues were collected at various time intervals during the experiment to test for infectious bursal disease virus (IBDV)-RNA by using reverse transcriptase-polymerase ...

  15. Human Papillomavirus Vaccination at a Time of Changing Sexual Behavior.

    Science.gov (United States)

    Baussano, Iacopo; Lazzarato, Fulvio; Brisson, Marc; Franceschi, Silvia

    2016-01-01

    Human papillomavirus (HPV) prevalence varies widely worldwide. We used a transmission model to show links between age-specific sexual patterns and HPV vaccination effectiveness. We considered rural India and the United States as examples of 2 heterosexual populations with traditional age-specific sexual behavior and gender-similar age-specific sexual behavior, respectively. We simulated these populations by using age-specific rates of sexual activity and age differences between sexual partners and found that transitions from traditional to gender-similar sexual behavior in women sexual behavior and that increased risk for HPV infection attributable to transition is preventable by early vaccination. Our study highlights the importance of using time-limited opportunities to introduce HPV vaccination in traditional populations before changes in age-specific sexual patterns occur.

  16. Polymer hydrogels: Chaperoning vaccines

    Science.gov (United States)

    Staats, Herman F.; Leong, Kam W.

    2010-07-01

    A cationic nanosized hydrogel (nanogel) shows controlled antigen delivery in vivo following intranasal administration and hence holds promise for a clinically effective adjuvant-free and needle-free vaccine system.

  17. Non-specific Effects of Vaccines and Stunting: Timing May Be Essential

    Directory of Open Access Journals (Sweden)

    Mike L.T. Berendsen

    2016-06-01

    Conclusions: We found a general time-dependent pattern of non-specific effects of vaccination, with positive associations for vaccinations given early in life and negative associations for vaccinations given later in infancy. If confirmed in further research, our findings may provide a new perspective on the non-specific effects of vaccination.

  18. Improved coverage and timing of childhood vaccinations in two post-Soviet countries, Armenia and Kyrgyzstan.

    Science.gov (United States)

    Schweitzer, A; Krause, G; Pessler, F; Akmatov, M K

    2015-08-19

    Timing of childhood vaccinations has received close attention in many countries. Little is known about the trends in correctly timed vaccination in former Soviet countries. We examined trends in vaccination coverage and correct timing of vaccination in two post-Soviet countries, Armenia and Kyrgyzstan, and analyzed factors associated with delayed vaccinations. We used data from the Demographic and Health Surveys; the surveys were conducted in 2000 (n = 1726), 2005 (n = 1430) and 2010 (n = 1473) in Armenia and in 1997 (n = 1127) and 2012 (n = 4363) in Kyrgyzstan. We applied the Kaplan-Meier method to estimate age-specific vaccination coverage with diphtheria, tetanus and pertussis (DTP) vaccine and a measles-containing vaccine (MCV). A Cox proportional hazard regression with shared frailty was used to examine factors associated with delayed vaccinations. Vaccination coverage for all three doses of the DTP vaccine increased in Armenia from 92 % in 2000 to 96 % in 2010. In Kyrgyzstan, DTP coverage was 96 % and 97 % in 1997 and 2012, respectively. Vaccination coverage for MCV increased from 89 % (Armenia, 2000) and 93 % (Kyrgyzstan, 1997) to 97 % (Armenia, 2010) and 98 % (Kyrgyzstan, 2012). The proportion of children with correctly timed vaccinations increased over time for all examined vaccinations in both countries. For example, the proportion of children in Armenia with correctly timed first DTP dose (DTP1) increased from 46 % (2000) to 66 % (2010). In Kyrgyzstan, the proportion of correctly timed DTP1 increased from 75 % (1997) to 87 % (2012). In Armenia, delays in the third DTP dose (DTP3) and MCV vaccinations were less likely to occur in the capital, whereas in Kyrgyzstan DTP3 and MCV start was delayed in the capital compared to other regions of the country. Also, in Armenia living in urban areas was associated with delayed vaccinations. Vaccination coverage and timing of vaccination improved over the last years in both countries. Further

  19. Hepatitis B vaccination timing: results from demographic health surveys in 47 countries

    Science.gov (United States)

    Akmatov, Manas K; Krause, Gérard

    2017-01-01

    Abstract Objective To examine the impact of hepatitis B vaccination schedules and types of vaccines on hepatitis B vaccination timing. Methods We used data for 211 643 children from demographic and health surveys in 47 low- and middle-income countries (median study year 2012). Data were from vaccination cards and maternal interviews. We grouped countries according to the vaccination schedule and type of vaccine used (monovalent or combination). For each country, we calculated hepatitis B vaccination coverage and timely receipt of vaccine doses. We used multivariable logistic regression models to study the effect of vaccination schedules and types on vaccination delay. Findings Substantial delays in vaccination were observed even in countries with fairly high coverage of all doses. Median delay was 1.0 week (interquartile range, IQR: 0.3 to 3.6) for the first dose (n = 108 626 children) and 3.7 weeks (IQR: 1.4 to 9.3) for the third dose (n = 101  542). We observed a tendency of lower odds of delays in vaccination schedules starting at 6 and at 9 weeks of age. For the first vaccine dose, we recorded lower odds of delays for combination vaccines than for monovalent vaccines (adjusted odds ratio, aOR: 0.76, 95% confidence interval, CI: 0.71 to 0.81). Conclusion Wide variations in hepatitis B vaccination coverage and adherence to vaccination schedules across countries underscore the continued need to strengthen national immunization systems. Timely initiation of the vaccination process might lead to timely receipt of successive doses and improved overall coverage. We suggest incorporating vaccination timing as a performance indicator of vaccination programmes to complement coverage metrics. PMID:28250533

  20. [The time course of changes in cell immunological parameters during administration of live dry plague vaccine].

    Science.gov (United States)

    Bogacheva, N V; Darmov, I V; Borisevich, I V; Kriuchkov, A V; Pechenkin, D V

    2009-08-01

    The study of the time course of changes in cell immunological parameters by a magnetic separation technique in human beings during the administration of plague vaccine in relation to the immunological load revealed the higher blood levels of all T lymphocyte subpopulations on day 14 after vaccination. These changes are most typical of a primary vaccinated cohort. The increased frequency of plague vaccine administration and multiple immunizations with live plague, anthrax, and tularemia vaccines produce the time-course of changes in T lymphocyte populations (subpopulations) in response to the regular administration of plague vaccine. A high immunological load in man also promotes a significant reduction in the level of B lymphocytes.

  1. CT of intranasal pleomorphic adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Clark, M.; Fatterpekar, G.M.; Mukherji, S.K.; Buenting, J. [Department of Radiology, 3324 Infirmary CB F 7510, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7510 (United States)

    1999-08-01

    Intranasal pleomorphic adenoma is rare. We report the CT features this tumor in a 41-year-old woman who presented to us with right nasal obstruction and a 2-day history of epistaxis. (orig.) With 3 figs., 9 refs.

  2. Marketing research on intranasal medicines of domestic market

    Directory of Open Access Journals (Sweden)

    B. S. Burlaka

    2016-12-01

    Full Text Available Modern development of biopharmaceutical research in world science and practice promotes the use of new dosage forms or administration routes of active substances in the human body. Recently, researchers drew attention to the use of non-invasive route of administration that can be used for new drug substances and for existing ones. Non-invasive routes of drugs’ administration have some advantages over invasive one, namely: do not damage the skin, do not require special training and conditions of use, provide the appropriate level of therapeutic efficacy of medicinal products. One of these administration routes of active substances in the human body is the intranasal one. Intranasal formulations have been known for a long time, most of them are widely used for topical treatment of various diseases of the nasal cavity. In recent decades, scientists have positive results on the use of intranasal route for regular use. Nasal medicines for systemic use are also easy to use; they do not cause irritation of the gastrointestinal tract. While intranasal route of administration the active ingredients fall directly into the general circulation and unlike enteral route they escape the first-pass elimination, which prevents the premature destruction of the drug. Objective: marketing research on registered intranasal drugs for local and systemic applications of the domestic market. Materials and Methods: Official data from the Ukrainian State Register of medicines, with details to release forms of the drug, dosage, manufacturer, country of origin and pharmacotherapeutic group has been used as a research material. Results. According to the State Register of medicinal products 226 intranasal drugs of the domestic market are recorded. Conclusions. Marketing research on intranasal drugs for local and systemic applications of the domestic market has been performed. It has been found that vast majority – 94.7% among registered intranasal drugs are the medicines

  3. Infant vaccination timing: Beyond traditional coverage metrics for maximizing impact of vaccine programs, an example from southern Nepal.

    Science.gov (United States)

    Hughes, Michelle M; Katz, Joanne; Englund, Janet A; Khatry, Subarna K; Shrestha, Laxman; LeClerq, Steven C; Steinhoff, Mark; Tielsch, James M

    2016-02-10

    Immunization programs currently measure coverage by assessing the proportion of children 12-24 months who have been immunized but this does not address the important question of when the scheduled vaccines were administered. Data capturing the timing of vaccination in first 6 months, when severe disease is most likely to occur, are limited. To estimate the time to Bacillus Calmette-Guérin (BCG) (recommended at birth), diphtheria-tetanus-pertussis-H, influenza b-hepatitis B (DTP-Hib-HepB), and oral polio vaccine (OPV) (recommended at 6, 10, and 14 weeks) vaccinations and risk factors for vaccination delay in infants vaccination were visited weekly at home from birth through age 6 months to ascertain if any vaccinations had been given in the prior week. Infant, maternal, and household characteristics were recorded. BCG, DTP-Hib-HepB, and OPV vaccination coverage at 4 and 6 months was estimated. Time to vaccination was estimated through Kaplan-Meier curves; Cox-proportional hazards models were used to examine risk factors for delay for the first vaccine. The median age of BCG, first OPV and DTP-Hib-HepB receipt was 22, 21, and 18 weeks, respectively. Almost half of infants received no BCG by age 6 months. Only 8% and 7% of infants had received three doses of OPV and DTP-Hib-HepB, respectively, by age 6 months. A significant delay in receipt of infant vaccines was found in a prospective, population-based, cohort in southern Nepal despite traditional coverage metrics being high. Immunization programs should consider measuring time to receipt relative to the official schedule in order to maximize benefits for disease control and child health. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Intranasal delivery of antipsychotic drugs.

    Science.gov (United States)

    Katare, Yogesh K; Piazza, Justin E; Bhandari, Jayant; Daya, Ritesh P; Akilan, Kosalan; Simpson, Madeline J; Hoare, Todd; Mishra, Ram K

    2017-06-01

    Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses. We also review clinical studies in which intranasal delivery of peptides, like oxytocin (7 studies) and desmopressin (1), were used as an adjuvant to antipsychotic treatment with promising results. Experimental animal studies (17) investigating intranasal delivery of mainstream antipsychotic drugs have revealed successful targeting to the brain as suggested by pharmacokinetic parameters and behavioral effects. To improve delivery to the brain, nanotechnology-based carriers like nanoparticles and nanoemulsions have been used in several studies. However, human studies assessing intranasal delivery of mainstream antipsychotic drugs are lacking, and the potential toxicity of nanoformulations used in animal studies has not been explored. A brief discussion of future directions anticipates that if limitations of low aqueous solubility of antipsychotic drugs can be overcome and non-toxic formulations used, IN delivery (particularly targeting specific tissues within the brain) will gain more importance moving forward given the inherent benefits of IN delivery in comparison to other methods. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Attitudes and beliefs of parents concerned about vaccines: impact of timing of immunization information.

    Science.gov (United States)

    Vannice, Kirsten S; Salmon, Daniel A; Shui, Irene; Omer, Saad B; Kissner, Jennifer; Edwards, Kathryn M; Sparks, Robert; Dekker, Cornelia L; Klein, Nicola P; Gust, Deborah A

    2011-05-01

    To determine if giving vaccine-information materials before the 2-month vaccination visit to mothers with concerns about vaccine safety positively changed their attitudes and beliefs about vaccine safety. Mothers who indicated concerns about infant vaccinations were recruited from 2 separate sites in Tennessee and California and were given vaccine information at 1 of 3 times: during a prenatal visit; a 1-week postpartum well-child visit; or a 2-month vaccination visit. A separate group of concerned mothers was assigned to be followed longitudinally at all 3 time points and was analyzed separately. The mothers reviewed a new vaccine-information pamphlet and Vaccine Information Statements (VIS) from the Centers for Disease Control and Prevention. Attitudes and beliefs about immunization were assessed both before and after the review of materials with written surveys. A total of 272 mothers with immunization concerns participated in the study. After review of the materials, mothers in all groups were significantly more likely to respond positively to questions and statements supporting the safety and importance of vaccines. Mothers who received this information at earlier visits were not significantly more likely to respond positively than mothers who received the information at the child's 2-month vaccination visit; however, participating mothers did indicate a preference for receiving vaccine information before the first vaccination visit. Distribution of the vaccine-information pamphlet and Vaccine Information Statements significantly improved attitudes about vaccination regardless of at what visit they were provided. Allowing adequate time to review vaccine information, even if done at the vaccination visit, may benefit concerned mothers.

  6. Intranasal immunization with recombinant HA and mast cell activator C48/80 elicits protective immunity against 2009 pandemic H1N1 influenza in mice.

    Directory of Open Access Journals (Sweden)

    Shu Meng

    Full Text Available BACKGROUND: Pandemic influenza represents a major threat to global health. Vaccination is the most economic and effective strategy to control influenza pandemic. Conventional vaccine approach, despite being effective, has a number of major deficiencies including limited range of protection, total dependence on embryonated eggs for production, and time consuming for vaccine production. There is an urgent need to develop novel vaccine strategies to overcome these deficiencies. METHODOLOGY/PRINCIPAL FINDINGS: The major objective of this work was to develop a novel vaccine strategy combining recombinant haemagglutinin (HA protein and a master cell (MC activator C48/80 for intranasal immunization. We demonstrated in BALB/c mice that MC activator C48/80 had strong adjuvant activity when co-administered with recombinant HA protein intranasally. Vaccination with C48/80 significantly increased the serum IgG and mucosal surface IgA antibody responses against HA protein. Such increases correlated with stronger and durable neutralizing antibody activities, offering protection to vaccinated animals from disease progression after challenge with lethal dose of A/California/04/2009 live virus. Furthermore, protected animals demonstrated significant reduction in lung virus titers, minimal structural alteration in lung tissues as well as higher and balanced production of Th1 and Th2 cytokines in the stimulated splenocytes when compared to those without C48/80. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that the novel vaccine approach of combining recombinant HA and mucosal adjuvant C48/80 is safe and effective in eliciting protective immunity in mice. Future studies on the mechanism of action of C48/80 and potential combination with other vaccine strategies such as prime and boost approach may help to induce even more potent and broad immune responses against viruses from various clades.

  7. Optimizing Real-Time Vaccine Allocation in a Stochastic SIR Model.

    Directory of Open Access Journals (Sweden)

    Chantal Nguyen

    Full Text Available Real-time vaccination following an outbreak can effectively mitigate the damage caused by an infectious disease. However, in many cases, available resources are insufficient to vaccinate the entire at-risk population, logistics result in delayed vaccine deployment, and the interaction between members of different cities facilitates a wide spatial spread of infection. Limited vaccine, time delays, and interaction (or coupling of cities lead to tradeoffs that impact the overall magnitude of the epidemic. These tradeoffs mandate investigation of optimal strategies that minimize the severity of the epidemic by prioritizing allocation of vaccine to specific subpopulations. We use an SIR model to describe the disease dynamics of an epidemic which breaks out in one city and spreads to another. We solve a master equation to determine the resulting probability distribution of the final epidemic size. We then identify tradeoffs between vaccine, time delay, and coupling, and we determine the optimal vaccination protocols resulting from these tradeoffs.

  8. Development of a Vaccine for Neisseria Meningitidis Group B Based on Native Outer Membrane Vesicles

    National Research Council Canada - National Science Library

    Zollinger, W. D; Fisseha, M; Brandt, B. L; Drabick, J

    2006-01-01

    ...) as a vaccine have been investigated. The first is intranasal vaccination using NOMV prepared from a capsule negative mutant, and the second is intramuscular vaccination using NOMV prepared from a double mutant that is capsule negative...

  9. Timely measles vaccination in Tianjin, China: a cross-sectional study of immunization records and mothers.

    Science.gov (United States)

    Wagner, Abram L; Zhang, Ying; Montgomery, JoLynn P; Ding, Yaxing; Carlson, Bradley F; Boulton, Matthew L

    2014-08-29

    Measles is a highly infectious disease, and timely administration of two doses of vaccine can ensure adequate protection against measles for all ages in a population. This study aims to estimate the proportion of children aged 8 months to 6 years vaccinated on time with measles-containing vaccines (MCV) and vaccinated during the 2008 and 2010 measles supplementary immunization activities. This study also characterizes differences in mean age at vaccination and vaccination timeliness by demographic characteristics, and describes maternal knowledge of measles vaccination. Immunization records were selected from a convenience sample of immunization clinics in Tianjin, China. From the records, overall vaccination coverage and timely vaccination coverage were calculated for different demographic groups. Mothers were also interviewed at these clinics to ascertain their knowledge of measles vaccination. Within the 329 immunization clinic records, child's birth year and district of residence were found to be significant predictors of different measures of vaccine timeliness. Children born in 2009 had a lower age at MCV dose 2 administration (17.96 months) than children born in 2005 (22.00 months). Children living in Hebei, a district in the urban center of Tianjin were less likely to be vaccinated late than children living in districts further from the urban core of Tianjin. From the 31 interviews with mothers, most women believed that timely vaccination was very important and more than one dose was very necessary; most did not know whether their child needed another dose. When reviewing MCV coverage in China, most studies do not consider timeliness. However, this study shows that overall vaccination coverage can greatly overestimate vaccination coverage within certain segments of the population, such as young infants.

  10. Evaluation of timing of first vaccination in children after hematopoietic allogeneic stem cell transplantation.

    Science.gov (United States)

    Bauters, Tiene; Bordon Cueto De Braem, Victoria; Schelstraete, Petra; Van Lancker, Sophie; Laureys, Geneviève; Benoit, Yves; Dhooge, Catharina

    2016-04-01

    Protective immunity to vaccine preventable infectious diseases might be lost over time following hematopoietic stem cell transplantation (HSCT). Limited data are available on the appropriate follow-up of vaccination schedules in pediatric HSCT patients. This study aims to ascertain whether the guidelines for vaccination recommended in our hospital are followed and to which extent of conformity they are used. A 5-year survey, including all pediatric allogeneic HSCT patients, transplanted at the Ghent University hospital, Belgium. Data were collected from the patient's electronic (nursing and medical) charts. Data on vaccination schedules of 28 patients (54.9%) eligible for the recommended vaccinations were collected. Eleven patients (11/28; 39.3%) were vaccinated timely. In 14 out of 17 patients (82.4%) vaccination was postponed for medical reasons, while vaccination was postponed without medical reason in 17.6% (3/17). Vaccination data could not be retrieved in 43.1 (22/51) of patients. Vaccination was declined by the parents in one patient (2.0%). There is high level of agreement between the hospital guideline and the vaccination of pediatric HSCT patients. Health-care providers play a crucial role in effectively appropriate follow-up of vaccination schedules. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The use of reimbursement data for timely monitoring of vaccination coverage: the example of human papillomavirus vaccine following public concerns about vaccine safety.

    Science.gov (United States)

    Fonteneau, Laure; Ragot, Marine; Parent du Châtelet, Isabelle; Guthmann, Jean-Paul; Lévy-Bruhl, Daniel

    2015-12-12

    Since 2011 public concerns about Human Papillomavirus (HPV) vaccination safety and efficacy arose in France. We explored the relevance of using vaccines reimbursement data to assess the impact of those public concerns on vaccination coverage. We used the Permanent Sample of Beneficiaries which was, at the time of the study, a representative sample of 1/97(th) health insurance beneficiaries of the main Social Security scheme, the General Health Insurance Scheme, covering approximately 77 % of the French resident population. We estimated HPV vaccination coverage among girls born between 1995 and 1999 at their 15(th), 16(th) and 17(th) birthday. The coverage for complete vaccination among 16 years old girls decreased from 26.5 % in the first semester of 2011 to 18.6 % in the first semester of 2014. HPV vaccination coverage was already low in 2011 and continued to decrease thereafter. Vaccines reimbursement data allowed us to reactively monitor the impact of the controversy on vaccination coverage and design counteracting measures.

  12. Population Pharmacokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  13. Immunity Response of Gumboro and ND Vaccination Result Which Given with TIME Spacing in Broiler Chicken

    OpenAIRE

    Yuwono, Endro; Setyawati, SJA

    2001-01-01

    An experiment was planed to know  the possibility of negative effect on Gumboro vaccination program. This program has a possibility to cause “Sick” condition on fabrious bursal of broiler chicken. From that case, it need time spacing for subsequent vaccination program, for instance ND vaccination program.  Time spacing is very importance to broiler chicken for recovering that “Sick” condition because of Gumboro vaccination effect. The purpose of his research was to know the best time spacing ...

  14. Glucose recovery after intranasal glucagon during hypoglycaemia in man

    DEFF Research Database (Denmark)

    Hvidberg, A; Djurup, R; Hilsted, J

    1994-01-01

    We compared the hyperglycaemic effect of intranasal and intramuscular (i.m.) administration of glucagon after insulin-induced hypoglycaemia. Twelve healthy subjects were examined twice, receiving on both occasions an intravenous insulin bolus. Somatostatin and propranolol were administered to block...... endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose...... concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose...

  15. Assessing and responding in real time to online anti-vaccine sentiment during a flu pandemic.

    Science.gov (United States)

    Seeman, Neil; Ing, Alton; Rizo, Carlos

    2010-01-01

    The perceived safety of vaccination is an important explanatory factor for vaccine uptake and, consequently, for rates of illness and death. The objectives of this study were (1) to evaluate Canadian attitudes around the safety of the H1N1 vaccine during the fall 2009 influenza pandemic and (2) to consider how public health communications can leverage the Internet to counteract, in real time, anti-vaccine sentiment. We surveyed a random sample of 175,257 Canadian web users from October 27 to November 19, 2009, about their perceptions of the safety of the HINI vaccine. In an independent analysis, we also assessed the popularity of online flu vaccine-related information using a tool developed for this purpose. A total of 27,382 unique online participants answered the survey (15.6% response rate). Of the respondents, 23.4% considered the vaccine safe, 41.4% thought it was unsafe and 35.2% reported ambivalence over its safety. Websites and blog posts with anti-vaccine sentiment remained popular during the course of the pandemic. Current public health communication and education strategies about the flu vaccine can be complemented by web analytics that identify, track and neutralize anti-vaccine sentiment on the Internet, thus increasing perceived vaccine safety. Counter-marketing strategies can be transparent and collaborative, engaging online "influencers" who spread misinformation.

  16. Maternal determinants of timely vaccination coverage among infants in rural Bangladesh.

    Science.gov (United States)

    Vasudevan, Lavanya; Labrique, Alain B; Mehra, Sucheta; Wu, Lee; Levine, Orin; Feikin, Danny; Klemm, Rolf; Christian, Parul; West, Keith P

    2014-09-22

    Timely vaccination, i.e., the receipt of all scheduled vaccinations in an age-appropriate fashion, is critical for the prevention of deadly diseases in infants and achievement of the UN Millennium Development Goal to reduce infant mortality. Infants, especially in rural or underprivileged settings often receive delayed vaccinations leaving them susceptible to vaccine-preventable illnesses early in the first year of life. In this study, we examined rates of timely vaccination among 24,435 infants born in Gaibandha and Rangpur rural districts of Bangladesh from 2001 to 2007. Vaccinations due by 14 weeks of age and administered through routine government immunization services were assessed using interviews with enrolled mothers between 11 and 18 weeks postpartum. We created a Timely Vaccination (TV) score to classify infants as vaccinated fully and on schedule (TV=1) or not (TV=0), and used multivariable logistic regression to identify maternal characteristics associated with infant's timely vaccination status. Our results suggest that only 19% of infants in this cohort received scheduled vaccinations on time by 11-18 weeks postpartum. Mothers' engagement in paid employment [OR=1.13, 95% CI: 1.03-1.23], receipt of tetanus toxoid vaccination [OR=1.24, 95% CI: 1.11-1.38], history of antenatal care [OR=1.22, 95% CI: 1.12-1.32], or higher socioeconomic status [OR=1.07, 95% CI: 1.03-1.11] were positively associated with timely vaccination of their infants. Mother's perception of small infant size at birth was negatively associated with timely vaccination [OR=0.89, 95% CI: 0.82-0.97]. Timely vaccination coverage of infants in rural Gaibandha and Rangpur districts is extremely low. This analysis identifies important shortcomings associated with the 1-year vaccination benchmark of routine immunization performance and suggests the need for specific interventions based on potential maternal determinants as well as known system and programmatic barriers of timely vaccination

  17. Intranasal immunization with LACK-DNA promotes protective immunity in hamsters challenged with Leishmania chagasi.

    Science.gov (United States)

    DE Oliveira Gomes, Daniel Claudio; DA Silva Costa Souza, Beatriz Lilian; DE Matos Guedes, Herbert Leonel; Lopes, Ulisses Gazos; Rossi-Bergmann, Bartira

    2011-12-01

    LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in protozoans of the genus Leishmania which is associated with the immunopathogenesis and susceptibility of BALB/c mice to L. major infection. Previously, we demonstrated that intranasal immunization with a plasmid carrying the LACK gene of Leishmania infantum (LACK-DNA) promotes protective immunity in BALB/c mice against Leishmania amazonensis and Leishmania chagasi. In the present study, we investigated the protective immunity achieved in hamsters intranasally vaccinated with 2 doses of LACK-DNA (30 μg). Compared with controls (PBS and pCI-neo plasmid), animals vaccinated with LACK-DNA showed significant reduction in parasite loads in the spleen and liver, increased lymphoproliferative response and increased nitric oxide (NO) production by parasite antigen-stimulated splenocytes. Furthermore, hamsters vaccinated with LACK-DNA presented high IgG and IgG2a serum levels when compared to control animals. Our results showed that intranasal vaccination with LACK-DNA promotes protective immune responses in hamsters and demonstrated the broad spectrum of intranasal LACK-DNA efficacy in different host species, confirming previous results in murine cutaneous and visceral leishmaniasis.

  18. Is It Time for Vaccination to "Go Viral"?

    Science.gov (United States)

    Philip, Roy K; Shapiro, Marla; Paterson, Pauline; Glismann, Steffen; Van Damme, Pierre

    2016-12-01

    To promote and sustain excellent vaccination coverage, while preserving the key core values of ethics, truth, transparency and trust, the vaccine community should adopt modern digital communication strategies. This article summarizes our views-as experts in multidisciplinary field of vaccinology (consisting of an anthropologist, a public health policy advisor, a vaccine industry expert, a health care journalist and a practicing physician)-which were presented at a satellite symposium held at the 33rd European Society of Paediatric Infectious Disease conference in Leipzig, Germany, in May 2015. This article aims to suggest and recommend strategies to promote vaccination awareness, and highlight proactive measures for building, maintaining and enhancing trust in vaccination through innovative communication and evidence-based interaction with the end user. We believe that converting the results of vaccine research into a successful vaccination program, and replacing misinformation with evidence-based communication, will require a multidisciplinary approach that embraces modern digital and tailored applications to reach out to all populations.

  19. Parental migration and children's timely measles vaccination in rural China: a cross-sectional study.

    Science.gov (United States)

    Tang, Xianyan; Geater, Alan; McNeil, Edward; Zhou, Hongxia; Deng, Qiuyun; Dong, Aihu; Li, Qiao

    2016-07-01

    With the rapid economic development in China, millions of rural residents are migrating to the cities to gain employment, resulting in numerous left-behind children (LBC). Simultaneously, outbreaks of measles continue to occur, yet the effect of parental migration on children's vaccination status is largely unknown. This study aimed to evaluate the association between parental migration and children's timely measles vaccination in rural China, after adjusting for family socio-economic status (SES) indicators. We conducted a cross-sectional survey using multistage sampling among children aged 18-54 months in rural Guangxi of China. Information on measles vaccination status was obtained from the child's vaccination certificate, and data on SES were collected by interviewing the child's primary guardian. Family SES and vaccination coverage were compared between LBC and non-left-behind children (NLBC) using weighted logistic regression, while the delay in vaccination was compared using Kaplan-Meier survival analysis. Of the 1216 study children, 46% were LBC and 54% were NLBC. Compared to NLBC, the coverage of timely measles vaccination was significantly lower, and the median delay period was longer among LBC. After adjusting for SES indicators, LBC were significantly more likely to have an untimely vaccination for their first dose of measles vaccine than NLBC (OR = 1.33, 95% CI = 1.02-1.75). Due to the negative effect of parental migration and family SES, LBC were more likely to encounter serious delays of measles vaccination in rural China. Optimising vaccination policies could facilitate timely vaccination among LBC in rural China. © 2016 John Wiley & Sons Ltd.

  20. Coccyx fractures treated with intranasal calcitonin.

    Science.gov (United States)

    Foye, Patrick M; Shupper, Peter; Wendel, Ian

    2014-01-01

    Treating pain associated with acute coccyx fractures can be challenging. Intranasal calcitonin has been used to treat acute pain after vertebral fracture, and may even accelerate fracture healing. However, intranasal calcitonin has never previously been published as part of the treatment of acute coccyx fractures. To examine a series of cases in which intranasal calcitonin was used to treat coccydynia related to coccyx fractures. Case series and literature review. Outpatient university-based coccyx pain center. After use of intranasal calcitonin, pain levels decreased, adverse events were minimal, and the medication was generally well tolerated. As this is not a randomized control trial, the patients treated with intranasal calcitonin were not compared to a control group. Additionally, the sample size of 8 patients is relatively small. We propose that clinicians consider use of intranasal calcitonin for the treatment of pain due to acute coccyx fractures.

  1. Non-specific Effects of Vaccines and Stunting: Timing May Be Essential

    NARCIS (Netherlands)

    Berendsen, M.L.T.; Smits, J.P.J.M.; Netea, M.G.; Ven, A.J.A.M. van der

    2016-01-01

    BACKGROUND - Bacillus Calmette-Guérin (BCG) vaccination possesses effects on health beyond its target disease, the so called “non-specific effects”. We evaluate these effects, as well as the effect of timing of BCG and other vaccinations, on stunting in Sub-Saharan African (SSA) children under

  2. Non-specific Effects of Vaccines and Stunting: Timing May Be Essential

    NARCIS (Netherlands)

    Berendsen, M.L.; Smits, J.; Netea, M.G.; Ven, A. van der

    2016-01-01

    BACKGROUND: Bacillus Calmette-Guerin (BCG) vaccination possesses effects on health beyond its target disease, the so called "non-specific effects". We evaluate these effects, as well as the effect of timing of BCG and other vaccinations, on stunting in Sub-Saharan African (SSA) children under five.

  3. Intranasal immunization with novel EspA-Tir-M fusion protein induces protective immunity against enterohemorrhagic Escherichia coli O157:H7 challenge in mice.

    Science.gov (United States)

    Lin, Ruqin; Zhu, Bo; Zhang, Yiduo; Bai, Yang; Zhi, Fachao; Long, Beiguo; Li, Yawen; Wu, Yuhua; Wu, Xianbo; Fan, Hongying

    2017-04-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and hemolytic uremic syndrome in humans. Due to the risks associated with antibiotic treatment against EHEC O157:H7 infection, vaccines represent a promising method for prevention of EHEC O157:H7 infection. Therefore, we constructed the novel bivalent antigen EspA-Tir-M as a candidate EHEC O157:H7 subunit vaccine. We then evaluated the immunogenicity of this novel EHEC O157:H7 subunit vaccine. Immune responses to the fusion protein administered by intranasal and subcutaneous routes were compared in mice. Results showed higher levels of specific mucosal and systemic antibody responses induced by intranasal as compared to subcutaneous immunization. Intranasal immunization enhanced the concentration of interleukin-4, interleukin-10, and interferon-γ, while subcutaneous immunization enhanced only the latter two. In addition, intranasal immunization protected against EHEC O157:H7 colonization and infection in mice at a rate of 90%.Histopathological analysis revealed that vaccination reduced colon damage, especially when administered intranasally. In contrast, subcutaneous immunization elicited a weak immune response and exhibited a low protection rate. These findings demonstrate that intranasal immunization with the fusion protein induces both humoral and cellular immune (Th1/Th2) responses in mice. The novel EspA-Tir-M novel fusion protein therefore represents a promising subunit vaccine against EHEC O157:H7 infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...... was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4+Foxp3+ T cells and even more significant induction of γδ T cells in mucosal...

  5. Update on Intranasal Medications in Rhinosinusitis.

    Science.gov (United States)

    Snidvongs, Kornkiat; Thanaviratananich, Sanguansak

    2017-07-01

    This review describes beneficial effects and adverse events of various intranasal medications in treating rhinosinusitis. Application of intranasal steroids has been described in treating all subtypes of adult rhinosinusitis, but reports are limited in pediatrics and mostly in acute pediatric subgroups resulted in benefits While saline irrigation is effective for patients with chronic rhinosinusitis without polyps and in pediatric acute rhinosinusitis, there is no evidence yet for saline drips and sprays. Application of intranasal antifungals and nasal irrigation with surfactant brings more harm than benefits. There is no evidence supporting the use of intranasal antibiotics. We also review influence of devices, methods, and patient head position on nasal and paranasal sinus drug delivery.

  6. Porcine reproductive and respiratory syndrome virus infection at the time of porcine circovirus type 2 vaccination has no impact on vaccine efficacy.

    Science.gov (United States)

    Sinha, A; Shen, H G; Schalk, S; Beach, N M; Huang, Y W; Halbur, P G; Meng, X J; Opriessnig, T

    2010-12-01

    Several porcine circovirus type 2 (PCV2) vaccines are now commercially available and have been shown to be effective at decreasing the occurrence of porcine circovirus-associated disease (PCVAD). Many herds are coinfected with PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV). Some producers and veterinarians are concerned that if pigs are vaccinated for PCV2 at or near the time that they are typically infected with PRRSV, the efficacy of the PCV2 vaccine will be compromised. The impact of PRRSV on PCV2 vaccination is unclear and has not been investigated under controlled conditions. The objective of the present study was to determine whether the presence of PRRSV viremia has an effect on the efficacy of commercial PCV2 vaccinations. Three-week-old PCV2-negative conventional pigs with passively derived anti-PCV2 antibodies were either vaccinated with one of three commercial PCV2 vaccines or left nonvaccinated. A portion of the pigs were infected with PRRSV 1 week prior to PCV2 vaccination. To determine vaccine efficacy, a PCV2 challenge was conducted at 8 weeks of age. PCV2 vaccination, regardless of PRRSV infection status at the time of vaccination, was similarly effective in inducing an anti-PCV2 IgG response in the presence of maternally derived immunity and in protecting the pigs from PCV2 challenge, as determined by a reduction in the level of PCV2 viremia and a reduction in the prevalence and amount of PCV2 antigen in lymphoid tissues in vaccinated pigs compared to nonvaccinated pigs. The results indicate that acute PRRSV infection at the time of PCV2 vaccination has no adverse effect on PCV2 vaccine efficacy.

  7. Comparison of dexmedetomidine versus midazolam for intranasal ...

    African Journals Online (AJOL)

    not cause mucosal stimulation, making it suitable for intranasal administration in paediatric patients.9,10. Objective. The aim of this study was to compare the effect of dexmedetomidine versus midazolam for intranasal premedication in children posted for elective surgery on preoperative anxiety, sedation, heart rate.

  8. Adenovirus 2, Bordetella bronchiseptica, and Parainfluenza Molecular Diagnostic Assay Results in Puppies After vaccination with Modified Live Vaccines.

    Science.gov (United States)

    Ruch-Gallie, R; Moroff, S; Lappin, M R

    2016-01-01

    Canine adenovirus 2, parainfluenza, and Bordetella bronchiseptica cause respiratory disease in dogs, and each has a modified live intranasal vaccine available. Molecular diagnostic assays to amplify specific nucleic acids are available for each of these agents. If positive molecular diagnostic assay results are common after vaccination, the positive predictive value of the diagnostic assays for disease would be decreased. To determine the impact of administration of commercially available modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza vaccine has on the results of a commercially available PCR panel. Eight puppies from a research breeding facility negative for these pathogens. Blinded prospective pilot study. Puppies were vaccinated with a single dose of modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza and parenteral dose of adenovirus 2, canine distemper virus, and parvovirus. Nasal and pharyngeal swabs were collected on multiple days and submitted for PCR assay. Nucleic acids of all 3 organisms contained in the topical vaccine were detected from both samples multiple times through 28 days after vaccination with higher numbers of positive samples detected between days 3 and 10 after vaccination. Vaccine status should be considered when interpreting respiratory agent PCR results if modified live vaccines have been used. Development of quantitative PCR and wild-type sequencing are necessary to improve positive predictive value of these assays by distinguishing vaccinate from natural infection. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  9. Vaccinations

    Science.gov (United States)

    ... will not work well for all pets. Your veterinarian will determine a vaccination schedule most appropriate for ... programs, but in some instances may help your veterinarian determine if your pet has a reasonable expectation ...

  10. Observational study to estimate the changes in the effectiveness of bacillus Calmette-Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK.

    Science.gov (United States)

    Mangtani, Punam; Nguipdop-Djomo, Patrick; Keogh, Ruth H; Trinder, Lucy; Smith, Peter G; Fine, Paul Em; Sterne, Jonathan; Abubakar, Ibrahim; Vynnycky, Emilia; Watson, John; Elliman, David; Lipman, Marc; Rodrigues, Laura C

    2017-07-01

    Until recently, evidence that protection from the bacillus Calmette-Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK's universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. Two case-control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0-19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10-29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case-cohort analysis based on Cox regression. In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10-15 years after vaccination and 57% (95% CI 33% to 72%) 15-20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar

  11. [Real-time monitoring of anti-influenza vaccination in the 65 and over population in France based on vaccine sales].

    Science.gov (United States)

    Pivette, M; Auvigne, V; Guérin, P; Mueller, J E

    2017-04-01

    The aim of this study was to describe a tool based on vaccine sales to estimate vaccination coverage against seasonal influenza in near real-time in the French population aged 65 and over. Vaccine sales data available on sale-day +1 came from a stratified sample of 3004 pharmacies in metropolitan France. Vaccination coverage rates were estimated between 2009 and 2014 and compared with those obtained based on vaccination refund data from the general health insurance scheme. The seasonal vaccination coverage estimates were highly correlated with those obtained from refund data. They were also slightly higher, which can be explained by the inclusion of non-reimbursed vaccines and the consideration of all individuals aged 65 and over. We have developed an online tool that provides estimates of daily vaccination coverage during each vaccination campaign. The developed tool provides a reliable and near real-time estimation of vaccination coverage among people aged 65 and over. It can be used to evaluate and adjust public health messages. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration

    NARCIS (Netherlands)

    de Haan, Aalzen; Haijema, Bert Jan; Voorn, Petra; Meijerhof, Tjarko; van Roosmalen, Maarten L.; Leenhouts, Kees

    2012-01-01

    Administration of influenza vaccines through the intranasal (IN) route forms an attractive alternative to conventional intramuscular (IM) injection. It is not only a better accepted form of vaccine administration but it also has the potential to induce, in addition to systemic antibodies, local

  13. Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G.

    Directory of Open Access Journals (Sweden)

    Lauren G Holinka

    Full Text Available Prophylactic vaccination using live attenuated classical swine fever (CSF vaccines has been a very effective method to control the disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccination although the mechanisms mediating the protection are poorly characterized. Here we present the events occurring after the administration of our in-house developed live attenuated marker vaccine, FlagT4Gv. We previously reported that FlagT4Gv intramuscular (IM administered conferred effective protection against intranasal challenge with virulent CSFV (BICv as early as 7 days post-vaccination. Here we report that FlagT4Gv is able to induce protection against disease as early as three days post-vaccination. Immunohistochemical testing of tissues from FlagT4Gv-inoculated animals showed that tonsils were colonized by the vaccine virus by day 3 post-inoculation. There was a complete absence of BICv in tonsils of FlagT4Gv-inoculated animals which had been intranasal (IN challenged with BICv 3 days after FlagT4Gv infection, confirming that FlagT4Gv inoculation confers sterile immunity. Analysis of systemic levels of 19 different cytokines in vaccinated animals demonstrated an increase of IFN-α three days after FlagT4Gv inoculation compared with mock infected controls.

  14. Utility of Respiratory Vaccination With Recombinant Subunit Vaccines for Protection Against Pneumonic Plague

    Science.gov (United States)

    2002-01-01

    Immunity at mucosal sites can prevent pathogen infection of the host. A) oral poliovirus vaccine B) inhaled influenza vaccine C) kennel cough & Newcastle... vaccine : Respiratory Vaccination : Proof-of-Principle Experiments Species: Mus musculus, Swiss/Webster strain , adult, both sexes Experiment outline...IM/IM IM IN/IN IN IM/IN Challenge strain : Yersinia pestis CO92 Challenge dose: 100 LD50 IgG titers after vaccination using intranasal F1-V as a

  15. Decreased rhinovirus shedding after intranasal oxymetazoline application in adults with induced colds compared with intranasal saline.

    Science.gov (United States)

    Winther, Birgit; Buchert, Dagobert; Turner, Ronald B; Hendley, J Owen; Tschaikin, Marion

    2010-01-01

    Intranasal oxymetazoline (OMZ) is used as a decongestant during common colds. Recently, intracellular adhesion molecule (ICAM) 1 receptor expression in vitro has been shown to be diminished by OMZ. ICAM-1 is the major receptor used by rhinovirus to gain entry to human cells. The objective of this study was to assess the effect of OMZ on geometric mean titer of rhinovirus in nasal lavage fluid after rhinovirus inoculation. Volunteers with antibody titers of ≤1:4 to rhinovirus type 39 were enrolled in a randomized, reference-controlled, double-blind study. Beginning 3 hours after intranasal challenge with 100-300 tissue culture infectious dose (TCID)₅₀ of virus, subjects received active 0.05% OMZ (45 μL containing 22.5 μg of OMZ hydrochloride in citrate buffer) or reference control (physiological saline solution [PSS]) three times daily for 5 days. Rhinovirus was detected in fibroblast cultures. Geometric mean viral titer (log₁₀) in 34 rhinovirus-infected subjects receiving OMZ was 1.49 on day 2 compared with 2.24 in the 38 infected subjects receiving PSS (p = 0.04). On day 3, the mean titers were 1.45 and 2.08, respectively. Median length of viral shedding was 3.3 days (OMZ) and 3.4 (PSS). Duration of clinical illness was 6.1 days in both groups. Topical OMZ decreased viral titer on day 2 during experimental rhinovirus infection in normal volunteers.

  16. Intranasal glukagon til behandling af hypoglykaemi. En fremtidig behandlingsmulighed

    DEFF Research Database (Denmark)

    Carstens, S; Andersen, I; Gustafsson, Ida

    1994-01-01

    Nearly 10% of IDDM patients receiving conventional insulin treatment and about three times as many in intensive insulin therapy yearly experience severe hypoglycaemia (requiring external assistance) The conventional treatment of severe hypoglycaemia is glucagon given intramuscularly by a relative...... or glucose administered intravenously by a physician. These are however not optimal treatments. Obtaining intravenous access requires a medical doctor and glucagon injection is not always properly done by family members. Glucagon administered intranasally has been proven to raise blood glucose levels...

  17. Intranasal Insulin: A Novel Treatment for Gulf War Multisymptom Illness

    Science.gov (United States)

    2017-10-01

    different doses of intranasal insulin on other symptoms that are characteristic of or associated with CMI (e.g., fatigue, pain, sleep quality ...and mood and sleep problems (Proctor et al., 1998; Sullivan et al., 2003). Despite the passage of time, the symptom complex persists for many...paramount importance to identify effective, safe, and tolerable treatments for Gulf War CMI. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17

  18. PPS nanoparticles as versatile delivery system to induce systemic and broad mucosal immunity after intranasal administration.

    Science.gov (United States)

    Stano, Armando; van der Vlies, André J; Martino, Mikael M; Swartz, Melody A; Hubbell, Jeffrey A; Simeoni, Eleonora

    2011-01-17

    Degradable polymer nanoparticles (NPs, 50 nm) based on polypropylene sulfide (PPS) were conjugated to thiolated antigen and adjuvant proteins by reversible disulfide bonds and evaluated in mucosal vaccination. Ovalbumin was used as a model antigen, and antigen-conjugated NPs were administered intranasally in the mouse. We show penetration of nasal mucosae, transit via M cells, and uptake by antigen-presenting cells in the nasal-associated lymphoid tissue. Ovalbumin-conjugated NPs induced cytotoxic T lymphocytic responses in lung and spleen tissues, as well as humoral response in mucosal airways. Co-conjugation of the TLR5 ligand flagellin further enhanced humoral responses in the airways as well as in the distant vaginal and rectal mucosal compartments and induced cellular immune responses with a Th1 bias, in contrast with free flagellin. The PPS NP platform thus appears interesting as a platform for intranasally-administered mucosal vaccination for inducing broad mucosal immunity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Characteristics of Articles About Human Papillomavirus Vaccination in Japanese Newspapers: Time-Series Analysis Study.

    Science.gov (United States)

    Ueda, Nao; Yokouchi, Ryoki; Onoda, Taro; Ogihara, Atsushi

    2017-12-19

    Media coverage and reports have a major influence on individual vaccination and other health-related activities. People use the media to seek information and knowledge on health-related behaviors. They obtain health-related information from media such as television and newspapers, and they trust such information. While several studies have examined the relation between media coverage and individual health, there is a lack of studies that have analyzed media reports of health information. In particular, we have found no analyses related to cervical cancer (human papillomavirus [HPV]) vaccine. This study aimed to identify mentions of cervical cancer vaccine in Japan's printed news media and to determine their characteristics. We used the archival databases of 2 Japanese newspapers, Yomiuri Shimbun (Yomidasu Rekishikan) and Asahi Shimbun (Kikuzo II Visual), for text mining. First, we created a database by extracting articles published between January 1, 2007, and December 31, 2014, that matched the terms "cervical cancer" AND "vaccination" in a keyword search. Then, we tallied the extracted articles based on the month of publication and number of characters in order to conduct a time-series analysis. We extracted a total of 219 articles. Of these, 154 (70.3%) were positive and 51 (23.3%) were negative toward HPV vaccination. Of the 51 negative articles, 4 (7.8%) were published before June 2013, when routine vaccination was temporarily discontinued due to concerns regarding side effects, and 47 (92.2%) were published since then. The negative reports commonly cited side effects, although prior to June 2013, these issues were hardly mentioned. Although foreign media reports mentioned side effects before routine vaccination was temporarily discontinued, fewer articles mentioned side effects than recommendations for vaccination. Furthermore, on June 13, 2013, the World Health Organization's advisory body Global Advisory Committee on Vaccine Safety issued a statement

  20. Microneedle and mucosal delivery of influenza vaccines

    Science.gov (United States)

    Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

    2017-01-01

    In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

  1. Effect of vaccines and antivirals during the major 2009 A(H1N1 pandemic wave in Norway--and the influence of vaccination timing.

    Directory of Open Access Journals (Sweden)

    Birgitte Freiesleben de Blasio

    Full Text Available To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7-29.8%, with highest disease rates among children 0-14 years (43-44%. Vaccination started in week 43 and came too late to have a strong influence on the pandemic in Norway. Our results indicate that the countermeasures prevented approximately 11-12% of potential cases relative to an unmitigated pandemic. Vaccination was found responsible for roughly 3 in 4 of the avoided infections. An estimated 50% reduction in the clinical attack rate would have resulted from vaccination alone, had the campaign started 6 weeks earlier. Had vaccination been prioritized for children first, the intervention should have commenced approximately 5 weeks earlier in order to achieve the same 50% reduction. In comparison, we estimate that a non-adjuvanted vaccination program should have started 8 weeks earlier to lower the clinical attack rate by 50%. In conclusion, vaccination timing was a critical factor in relation to the spread of the 2009 A(H1N1 influenza. Our results also corroborate the central role of children for the transmission of A(H1N1 pandemic influenza.

  2. Timing and delay in children vaccination; evaluation of expanded program of immunization in outskirt of Iranian cities.

    Science.gov (United States)

    Rejali, Mehri; Mohammadbeigi, Abolfazl; Mokhtari, Mohsen; Zahraei, Seyed Mohsen; Eshrati, Babak

    2015-01-01

    Most studies evaluated the vaccine coverage, but the time of vaccination is important as coverage. This study was conducted to evaluate the Expanded Program of Immunization (EPI) in outskirt of Iranian cities regarding to incidence of delay vaccination among children less than 4 years. This cross sectional descriptive study was conducted among children 24-47 months old, living in the suburbs of five metropolises of Iran. Totally, 3610 eligible children selected with proportioned cluster sampling method and data of vaccination card extracted after interview with child parents. Delayed incidence rate reported and predictive factors assessed by Chi square test and Multivariate logistic regression. Overall, 56.6% to 93.2% vaccines were administered out of time. Delayed vaccination incidence with more than one-week delay varies from 5.5% to 74.9% for polio at birth and MMR2 at 18 month, respectively. Mother's educational level and birth order were the most important predictors of delayed vaccination. Incidence of delayed vaccination was enlarged by increasing birth order and decreased in lower educated mothers. Incidence rate of delayed vaccination is more than expectation. Regarding to high coverage vaccines in Iran, heath officers and health policy makers should attempt for on-time vaccination beside of high immunization coverage especially in slum areas with more concentrated immigrants due to low literature and crowded families.

  3. [Epidemiological characteristics of children aged 1-4 years without timely birth dose of hepatitis B vaccine vaccination in China, 2014].

    Science.gov (United States)

    Wang, F Z; Zhang, G M; Shen, L P; Liu, J H; Zheng, H; Wang, F; Miao, N; Sun, X J; Liang, X F; Cui, F Q

    2017-01-10

    Objective: To evaluate the epidemiological characteristics of the children aged 1-4 years without timely birth dose of hepatitis B vaccine (HepB(1)) vaccination. Methods: Based on the data from 160 disease surveillance points in 31 provinces of China, two-stage cluster random sampling was used to select the target population aged 1-4 years. A standard questionnaire was used to collect the information about the birth date, gender, ethnic group, place of birth, HepB immunization history of the children selected. A blood sample (3 ml) was taken from each subject for HBsAg testing. SAS software (Version 9.4) was used in our study. We analyzed the age, gender, ethnic group, area specific distributions of the children aged 1-4 years without timely HepB(1) vaccination and the influencing factors, and the relationship between the HepB(1) vaccination time and HBsAg prevalence rate. Results: A total of 12 587 children aged 1-4 years were analyzed and the non-timely HepB(1) vaccination rate was 10.12 % . The place of birth, ethnic group, urban/rural area, eastern/central/western area, age were the main influencing factor of the non-timely HepB(1) vaccination. The non-timely HepB(1) vaccination rate was higher in 3-4 years old children (11.13 % ) than in 1-2 years old children (8.97 % ), in rural area (12.05 % ) than in urban area (8.19 % ), in western area (13.41 % ) than in central area (9.27 % ) and eastern area (7.72 % ), in minority ethnic group (18.06 % ) than in Han ethnic group (8.77 % ) and in children born outside hospital (57.66 % ) than in children born in hospital (9.27 % ). The HBsAg prevalence rate among 1-4 years children was 0.31 % . The HBsAg prevalence rate of the children with timely HepB(1) vaccination (0.25 % ) was lower than that of the children without timely HepB(1) vaccination (0.89 % ). Conclusions: In China, the HBsAg prevalence rate among 1-4 years children with HepB vaccination decreased to vaccination rate reached to 90 % . We should strengthen

  4. Protection of a live Pasteurella multocida B:3,4 vaccine against haemorrhagic septicaemia in cattle

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    Adin Priadi

    2002-03-01

    Full Text Available Cross protection conferred by a live Pasteurella multocida B:3,4 vaccine to infection by P. multocida B:2, the haemorrhagis septicaemia causing bacteria in cattle was investigated. Intranasal aerogenic immunization and subcutaneous injection of the live vaccine were applied to groups I and II of 5 Bali cattle respectively. Another group (III of 5 cattle were vaccinated with standard oli adjuvant killed vaccine intramuscularly. Cattle were observed for clinical signs and body temperatures were measured. Sera were collected monthly for 12 month and kept at -200C for further testing by ELISA. No adverse sign was observed at cattle of groups I and II after vaccination with the live vaccine. Both intranasal and subcutaneous vaccination of live vaccine showed a similar serological response which started at month-5, peaked at month-(6-7 after vaccination and still sustained at the level above positive cut-off (88 ELISA Unit at the end of observation month-12. Cattle vaccinated with killed adjuvanted vaccine responded earlier, peaked at 5-6 month after vaccination and declined steadily till the end of investigation. At 6 and 12 months after vaccination catlle were challenged with P. multocida B:2. All vaccinated cattle challenged at 6 months (C-1 and 12 (C-2 months after vaccination survived and showed no clinical signs. Body temperatures of all vaccinated cattle were normal and ranged from 38.10C to 39.10C and 38.50C to 39.50C for cattle chalenged at C-1 and C-2 respectively. However, there was 1 cattle of group I at C-1 showed an initial increase of body temperature to 400C and decreased to normal at 42 hours after challenge. One catlle of group II had a body temperature of 40.70C detected at 5 hours post C-2 and reached a normal temperature at hour-11. Both unvaccinated cattle at C-1 and C-2 died and had body temperatures of 41.40C and 41.10C respectively at the time of death. This investigation shows that live vaccine P. multocida B:3,4 is safe and

  5. Intranasal Midazolam May Prevent Gagging Reflex: a Case Report

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    Meral Arslan Malkoc

    2013-10-01

    Full Text Available Background: Gagging can become a conditioned response that makes dental treatment difficult or impossible for both the individual and the dentist. The aim of this study is to report a 50 year old female and two children (15 and 11 years old with exaggerated gag reflex referred to Faculty of Dentistry of Selçuk University.Methods: During obtaining records, taking impression procedure was elicited the patients’ hypersensitive gagging reflex. Therefore, it was decided to administer intranasal midazolam to facilitate the taking of accurate dental impressions. After given verbal information about the procedure, 2.5 mg intranasal midazolam (Demizolam, Dem Medikal, Istanbul were applied incrementally in both nostrils.Results: Five minutes later; patients had no gagging reflex and allowed the clinician to take satisfying impressions. No serious adverse effects were observed and the patients remained cooperative during the entire procedure which was completed to the full satisfaction of all involved. The short absorption time and the fast relief process of anaesthetics transferred to the systemic circulatory system are important advantages of nasal application.Conclusions: Intranasal midazolam may be very useful for the treatment of gag reflex probably effecting on the depression of upper airway reflex sensitivity.

  6. Intranasal midazolam may prevent gagging reflex: a case report.

    Science.gov (United States)

    Malkoc, Meral Arslan; Demir, Necla; Ileri, Zehra; Erdur, Aybuke; Apiliogullari, Seza

    2013-01-01

    Gagging can become a conditioned response that makes dental treatment difficult or impossible for both the individual and the dentist. The aim of this study is to report a 50 year old female and two children (15 and 11 years old) with exaggerated gag reflex referred to Faculty of Dentistry of Selçuk University. During obtaining records, taking impression procedure was elicited the patients' hypersensitive gagging reflex. Therefore, it was decided to administer intranasal midazolam to facilitate the taking of accurate dental impressions. After given verbal information about the procedure, 2.5 mg intranasal midazolam (Demizolam, Dem Medikal, Istanbul) were applied incrementally in both nostrils. Five minutes later; patients had no gagging reflex and allowed the clinician to take satisfying impressions. No serious adverse effects were observed and the patients remained cooperative during the entire procedure which was completed to the full satisfaction of all involved. The short absorption time and the fast relief process of anaesthetics transferred to the systemic circulatory system are important advantages of nasal application. Intranasal midazolam may be very useful for the treatment of gag reflex probably effecting on the depression of upper airway reflex sensitivity.

  7. Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection.

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    Fenghua Zhang

    Full Text Available Maternally-derived antibodies (MDAs can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP or intranasal (IN route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition.

  8. Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

    Science.gov (United States)

    Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

    2017-12-01

    We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

  9. Intranasal co-administration with the mouse zona pellucida 3 expressing construct and its coding protein induces contraception in mice.

    Science.gov (United States)

    Zhang, Ailian; Li, Jinyao; Zhao, Gan; Geng, Shuang; Zhuang, Shuzhen; Wang, Bin; Zhang, Fuchun

    2011-09-09

    The zona pellucida 3 (ZP3), an autoantigen, once used to develop contraceptive vaccine has been faced a safety issue. Avoiding its pathogenic T cell activation, we intranasally co-delivered the mZP3 DNA- and protein-based vaccines in mice and observed that a higher level of sIgA and IgG antibodies in vaginal washes, bronchoalveolar lavages and serum and yielded a lower level of fertility and mean litter size. Importantly, histological analysis showed that normal follicular developments of the infertile mice were not disrupted in the co-delivered group. Thus, the intranasal co-delivery may present a safe strategy for the development of contraceptive vaccine. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah

    2015-01-01

    International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model...... with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high......-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital Ig...

  11. Comparison of Intranasal and Intravenous Diazepam on Status Epilepticus in Stroke Patients

    Science.gov (United States)

    Inokuchi, Ryota; Ohashi-Fukuda, Naoko; Nakamura, Kensuke; Wada, Tomoki; Gunshin, Masataka; Kitsuta, Yoichi; Nakajima, Susumu; Yahagi, Naoki

    2015-01-01

    Abstract Administering diazepam intravenously or rectally in an adult with status epilepticus can be difficult and time consuming. The aim of this study was to examine whether intranasal diazepam is an effective alternative to intravenous diazepam when treating status epilepticus. We undertook a retrospective cohort study based on the medical records of 19 stroke patients presenting with status epilepticus to our institution. We measured the time between arrival at the hospital, the intravenous or intranasal administration of diazepam, and the seizure termination. Intranasal diazepam was administered about 9 times faster than intravenous diazepam (1 vs 9.5 minutes, P = 0.001), resulting in about 3-fold reduction in the time to termination of seizure activity after arrival at the hospital (3 minutes compared with 9.5 minutes in the intravenous group, P = 0.030). No adverse effects of intranasal diazepam were evident from the medical records. Intranasal diazepam administration is safer, easier, and quicker than intravenous administration. PMID:25700327

  12. Ontology-based time information representation of vaccine adverse events in VAERS for temporal analysis.

    Science.gov (United States)

    Tao, Cui; He, Yongqun; Yang, Hannah; Poland, Gregory A; Chute, Christopher G

    2012-12-20

    The U.S. FDA/CDC Vaccine Adverse Event Reporting System (VAERS) provides a valuable data source for post-vaccination adverse event analyses. The structured data in the system has been widely used, but the information in the write-up narratives is rarely included in these kinds of analyses. In fact, the unstructured nature of the narratives makes the data embedded in them difficult to be used for any further studies. We developed an ontology-based approach to represent the data in the narratives in a "machine-understandable" way, so that it can be easily queried and further analyzed. Our focus is the time aspect in the data for time trending analysis. The Time Event Ontology (TEO), Ontology of Adverse Events (OAE), and Vaccine Ontology (VO) are leveraged for the semantic representation of this purpose. A VAERS case report is presented as a use case for the ontological representations. The advantages of using our ontology-based Semantic web representation and data analysis are emphasized. We believe that representing both the structured data and the data from write-up narratives in an integrated, unified, and "machine-understandable" way can improve research for vaccine safety analyses, causality assessments, and retrospective studies.

  13. Ontology-based time information representation of vaccine adverse events in VAERS for temporal analysis

    Directory of Open Access Journals (Sweden)

    Tao Cui

    2012-12-01

    Full Text Available Abstract Background The U.S. FDA/CDC Vaccine Adverse Event Reporting System (VAERS provides a valuable data source for post-vaccination adverse event analyses. The structured data in the system has been widely used, but the information in the write-up narratives is rarely included in these kinds of analyses. In fact, the unstructured nature of the narratives makes the data embedded in them difficult to be used for any further studies. Results We developed an ontology-based approach to represent the data in the narratives in a “machine-understandable” way, so that it can be easily queried and further analyzed. Our focus is the time aspect in the data for time trending analysis. The Time Event Ontology (TEO, Ontology of Adverse Events (OAE, and Vaccine Ontology (VO are leveraged for the semantic representation of this purpose. A VAERS case report is presented as a use case for the ontological representations. The advantages of using our ontology-based Semantic web representation and data analysis are emphasized. Conclusions We believe that representing both the structured data and the data from write-up narratives in an integrated, unified, and “machine-understandable” way can improve research for vaccine safety analyses, causality assessments, and retrospective studies.

  14. Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

    Science.gov (United States)

    Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

    2018-01-01

    Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p fentanyl and intravenous paracetamol in Wilson Sedation Scale (p fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Surgical treatment of a canine intranasal meningoencephalocele.

    Science.gov (United States)

    Martlé, Valentine A; Caemaert, Jacques; Tshamala, Mulenda; Van Soens, Iris; Bhatti, Sofie F M; Gielen, Ingrid; Piron, Koen; Chiers, Koen; Tiemessen, Ilse; Van Ham, Luc M

    2009-06-01

    To report the clinical signs, diagnosis, and surgical treatment of an intranasal meningoencephalocele in a dog. Case report. Female Border collie, 5 months old. A right intranasal meningoencephalocele was identified by computed tomography and magnetic resonance imaging. The lesion was approached by a modified transfrontal craniotomy. Surgical closure of the defect at the level of the cribriform plate and removal of extruded brain tissue resulted in regression of lacrimation and coincided with absence of seizuring. Treatment with phenobarbital was gradually reduced and stopped at 7 months after surgery. At 28 months the dog remained free of seizures. Meningoencephalocele, although rare, can cause seizures in dogs and can be treated surgically. A transfrontal craniotomy with excision of the meningoencephalocele and closure of the defect can be an effective treatment for an intranasal meningoencephalocele in dogs.

  16. HIV vaccine: it may take two to tango, but no party time yet

    Directory of Open Access Journals (Sweden)

    Paxton William A

    2009-10-01

    Full Text Available Abstract A press conference on Thursday September 24 in Bangkok, Thailand, released data that an experimental vaccine provided mild protection against HIV-1 infection. This is the first positive signal of any degree of vaccine efficacy in humans, more than a quarter-century after scientists discovered the virus that causes AIDS. The research was conducted by a team including Thai researchers, the U.S. Army and the U.S. National Institutes of Health. The RV144 Phase III clinical trial, which began in 2003, had been disparaged by many critics as a waste of time and money because each of the two components had been shown to produce no benefit as individual vaccines and because the scientific rationales behind the immunogens were just wrong. It was nevertheless speculated that using them together in the prime-boost scenario could be more effective, with the aim to induce heightened CD4+ cellular immune responses against the viral Envelope protein. This optimism seems to have been validated. In fact, this would not be the first time that the discovery of an effective vaccine relied as much on serendipity as opposed to scientific rationale. On the other hand, many questions remain about the RV144 trial, and these issues will be addressed in this editorial.

  17. HIV vaccine: it may take two to tango, but no party time yet

    Science.gov (United States)

    Berkhout, Ben; Paxton, William A

    2009-01-01

    A press conference on Thursday September 24 in Bangkok, Thailand, released data that an experimental vaccine provided mild protection against HIV-1 infection. This is the first positive signal of any degree of vaccine efficacy in humans, more than a quarter-century after scientists discovered the virus that causes AIDS. The research was conducted by a team including Thai researchers, the U.S. Army and the U.S. National Institutes of Health. The RV144 Phase III clinical trial, which began in 2003, had been disparaged by many critics as a waste of time and money because each of the two components had been shown to produce no benefit as individual vaccines and because the scientific rationales behind the immunogens were just wrong. It was nevertheless speculated that using them together in the prime-boost scenario could be more effective, with the aim to induce heightened CD4+ cellular immune responses against the viral Envelope protein. This optimism seems to have been validated. In fact, this would not be the first time that the discovery of an effective vaccine relied as much on serendipity as opposed to scientific rationale. On the other hand, many questions remain about the RV144 trial, and these issues will be addressed in this editorial. PMID:19818121

  18. Ear Infection and Vaccines

    Science.gov (United States)

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  19. Bacterium-like Particles for efficient immune stimulation of existing vaccines and new subunit vaccines in mucosal applications

    Directory of Open Access Journals (Sweden)

    Natalija eVan Braeckel-Budimir

    2013-09-01

    Full Text Available The successful development of a mucosal vaccine critically depends on the use of a safe and effective immunostimulant and/or carrier system. This review describes the effectiveness and mode of action of an immunostimulating particle derived from bacteria in mucosal subunit vaccines. The non-living particles, designated Bacterium-like Particles (BLPs are based on the food-grade bacterium Lactococcus lactis. The focus of the overview is on the development of intranasal BLP-based vaccines to prevent diseases caused by influenza and respiratory syncytial virus, and includes a selection of Phase I clinical data for the intranasal FluGEM vaccine.

  20. An update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.

    Science.gov (United States)

    Romano, Marta; Huygen, Kris

    2012-12-01

    Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.

  1. Time-Dependent Propensity Score for Assessing the Effect of Vaccine Exposure on Pregnancy Outcomes through Pregnancy Exposure Cohort Studies

    Directory of Open Access Journals (Sweden)

    Ronghui Xu

    2014-03-01

    Full Text Available Women are advised to be vaccinated for influenza during pregnancy and may receive vaccine at any time during their pregnancy. In observational studies evaluating vaccine safety in pregnancy, to account for such time-varying vaccine exposure, a time-dependent predictor can be used in a proportional hazards model setting for outcomes such as spontaneous abortion or preterm delivery. Also, due to the observational nature of pregnancy exposure cohort studies and relatively low event rates, propensity score (PS methods are often used to adjust for potential confounders. Using Monte Carlo simulation experiments, we compare two different ways to model the PS for vaccine exposure: (1 logistic regression treating the exposure status as binary yes or no; (2 Cox regression treating time to exposure as time-to-event. Coverage probability of the nominal 95% confidence interval for the exposure effect is used as the main measure of performance. The performance of the logistic regression PS depends largely on how the exposure data is generated. In contrast, the Cox regression PS consistently performs well across the different data generating mechanisms that we have considered. In addition, the Cox regression PS allows adjusting for potential time-varying confounders such as season of the year or exposure to additional vaccines. The application of the Cox regression PS is illustrated using data from a recent study of the safety of pandemic H1N1 influenza vaccine during pregnancy.

  2. Safety of intranasal human insulin: a review.

    Science.gov (United States)

    Schmid, Vera; Kullmann, Stephanie; Gfrörer, Wieland; Hund, Verena; Hallschmid, Manfred; Lipp, Hans-Peter; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas; Heni, Martin

    2018-03-06

    The nasal application of human insulin is frequently used for investigating brain insulin action. It is utilized in studies on the physiological role of insulin in the human brain as well as in therapeutic interventional trials and its effects have been investigated after both acute and long-term administration. This review aimed to assess the safety of intranasal human insulin in human studies and the temporal stability of nasal insulin sprays. The electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were excerpted. Thirty-eight studies on 1092 persons with acute application and 18 studies on 832 persons with treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycemia or severe adverse events were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other adverse events were less commonly reported. There are no reports of subjects who were excluded due to adverse events. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks revealed that it had a chemical stability of up to 57 days. Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns. There is, however, insufficient data to ensure long-term safety of this modality of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment. This article is protected by copyright. All rights reserved.

  3. Oxytocin intranasal administration as a new hope for hypogonadotropic hypogonadism patients.

    Science.gov (United States)

    Salehi, Mohammad Saied; Pandamooz, Sareh; Khazali, Homayoun

    2017-11-01

    Hypogonadotropic hypogonadism (HH) is a form of hypogonadism which also known as secondary or central hypogonadism. Congenital HH can occur due to defect in gonadotropin releasing hormone (GnRH) neurons, upstream regulators of GnRH neurons or pituitary gonadotropic cells. Testosterone or gonadotropins therapy are widely used to treat HH patients, however both have undesirable effects and GnRH treatment for HH patients is time and cost consuming. Direct delivery of therapeutics to the brain via the nasal route is located in the center of attention during the last decade and trial application of intranasal oxytocin as a method of enhancing social interactions are reported. It has been delineated that oxytocin stimulates GnRH release from the rat hypothalamic explants and intranasal applied oxytocin up-regulates GnRH expression in the male rat hypothalamus. Therefore application of intranasal oxytocin might be a new strategy to cure HH patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Clustered lot quality assurance sampling: a pragmatic tool for timely assessment of vaccination coverage.

    Science.gov (United States)

    Greenland, K; Rondy, M; Chevez, A; Sadozai, N; Gasasira, A; Abanida, E A; Pate, M A; Ronveaux, O; Okayasu, H; Pedalino, B; Pezzoli, L

    2011-07-01

    To evaluate oral poliovirus vaccine (OPV) coverage of the November 2009 round in five Northern Nigeria states with ongoing wild poliovirus transmission using clustered lot quality assurance sampling (CLQAS). We selected four local government areas in each pre-selected state and sampled six clusters of 10 children in each Local Government Area, defined as the lot area. We used three decision thresholds to classify OPV coverage: 75-90%, 55-70% and 35-50%. A full lot was completed, but we also assessed in retrospect the potential time-saving benefits of stopping sampling when a lot had been classified. We accepted two local government areas (LGAs) with vaccination coverage above 75%. Of the remaining 18 rejected LGAs, 11 also failed to reach 70% coverage, of which four also failed to reach 50%. The average time taken to complete a lot was 10 h. By stopping sampling when a decision was reached, we could have classified lots in 5.3, 7.7 and 7.3 h on average at the 90%, 70% and 50% coverage targets, respectively. Clustered lot quality assurance sampling was feasible and useful to estimate OPV coverage in Northern Nigeria. The multi-threshold approach provided useful information on the variation of IPD vaccination coverage. CLQAS is a very timely tool, allowing corrective actions to be directly taken in insufficiently covered areas. © 2011 Blackwell Publishing Ltd.

  5. Vaccination against pandemic influenza A/H1N1v in England: a real-time economic evaluation.

    Science.gov (United States)

    Baguelin, Marc; Hoek, Albert Jan Van; Jit, Mark; Flasche, Stefan; White, Peter J; Edmunds, W John

    2010-03-11

    Decisions on how to mitigate an evolving pandemic are technically challenging. We present a real-time assessment of the effectiveness and cost-effectiveness of alternative influenza A/H1N1v vaccination strategies. A transmission dynamic model was fitted to the estimated number of cases in real-time, and used to generate plausible autumn scenarios under different vaccination options. The proportion of these cases by age and risk group leading to primary care consultations, National Pandemic Flu Service consultations, emergency attendances, hospitalisations, intensive care and death was then estimated using existing data from the pandemic. The real-time model suggests that the epidemic will peak in early November, with the peak height being similar in magnitude to the summer wave. Vaccination of the high-risk groups is estimated to prevent about 45 deaths (80% credibility interval 26-67), and save around 2900 QALYs (80% credibility interval 1600-4500). Such a programme is very likely to be cost-effective if the cost of vaccine purchase itself is treated as a sunk cost. Extending vaccination to low-risk individuals is expected to result in more modest gains in deaths and QALYs averted. Extending vaccination to school-age children would be the most cost-effective extension. The early availability of vaccines is crucial in determining the impact of such extensions. There have been a considerable number of cases of H1N1v in England, and so the benefits of vaccination to mitigate the ongoing autumn wave are limited. However, certain groups appear to be at significantly higher risk of complications and deaths, and so it appears both effective and cost-effective to vaccinate them. The United Kingdom was the first country to have a major epidemic in Europe. In countries where the epidemic is not so far advanced vaccination of children may be cost-effective. Similar, detailed, real-time modelling and economic studies could help to clarify the situation.

  6. The protoxin Cry1Ac of Bacillus thuringiensis improves the protection conferred by intranasal immunization with Brucella abortus RB51 in a mouse model.

    Science.gov (United States)

    González-González, Edith; García-Hernández, Ana Lilia; Flores-Mejía, Raúl; López-Santiago, Rubén; Moreno-Fierros, Leticia

    2015-02-25

    Brucellosis is a zoonotic disease affecting many people and animals worldwide. Preventing this infection requires improving vaccination strategies. The protoxin Cry1Ac of Bacillus thuringiensis is an adjuvant that, in addition to increasing the immunogenicity of different antigens, has shown to be protective in different models of parasitic infections. The objective of the present study was to test whether the intranasal co-administration of pCry1Ac with the RB51 vaccine strain of Brucella abortus confers protection against an intranasal challenge with the virulent strain B. abortus 2308 in BALB/c mice. The results showed that co-administration of pCry1Ac and RB51, increased the immunoprotection conferred by the vaccine as evidenced by the following: (1) decrease of the splenic bacterial load when challenged intranasally with the virulent strain; (2) greater in vivo cytotoxic activity in response to the transference of previously infected cells; (3) further proliferation of cytotoxic TCD8+ cells in response to stimulation with heat-inactivated bacteria; (4) increased production of TNF-α and IFN-γ; and (5) significant IgG2a response. These results indicate that the use of the Cry1Ac protein as a mucosal adjuvant via the intranasal route can be a promising alternative for improving current RB51 vaccine against brucellosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. An increasing, potentially measles-susceptible population over time after vaccination in Korea.

    Science.gov (United States)

    Kang, Hae Ji; Han, Young Woo; Kim, Su Jin; Kim, You-Jin; Kim, A-Reum; Kim, Joo Ae; Jung, Hee-Dong; Eom, Hye Eun; Park, Ok; Kim, Sung Soon

    2017-07-24

    In Korea, measles occurs mainly in infants measles infection. Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012). The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined. Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. DNA vaccination of rainbow trout against viral hemorrhagic septicemia virus: A dose-response and time-course study

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Einer-Jensen, Katja; Martinussen, T.

    2000-01-01

    Viral hemorrhagic septicemia (VHS) in rainbow trout Oncorhynchus mykiss is caused by VHS virus (VHSV), which belongs to the rhabdovirus family. Among the different strategies for immunizing fish with a recombinant vaccine, genetic immunization has recently proven to be highly effective. To further...... investigate the potential for protecting fish against VHS by DNA vaccination, experiments were conducted to determine the amount of plasmid DNA needed for induction of protective immunity. The time to onset of immunity and the duration of protection following administration of a protective vaccine dose were...... serologically different from the isolate used for vaccine development. Following administration of 1 mug of a DNA vaccine, significant protection against VHS was observed in the fish as early as 8 d postvaccination. At 168 d postvaccination, the fish had increased in size by a factor of 10 and protection...

  9. Intranasal immunization of the combined lipooligosaccharide conjugates protects mice from the challenges with three serotypes of Moraxella catarrhalis.

    Directory of Open Access Journals (Sweden)

    Dabin Ren

    Full Text Available There are no licensed vaccines available against Moraxella catarrhalis, a significant human respiratory pathogen. Lipooligosaccharide (LOS based conjugate vaccines derived from individual serotype M. catarrhalis only showed partial protection coverage. A vaccine combining LOS conjugates of two or three serotypes might provide a broader protection.Mice were immunized intranasally with the combined conjugates consisting of LOS from serotype A and B or serotype A, B, and C followed by challenge with different M. catarrhalis strains of three serotypes. Mouse lungs, nasal washes, and sera were collected after each challenge for bacterial counts, histological evaluation, cytokine profiles, antibody level and binding activity determinations.Intranasal administration of the combined LOS conjugates not only enhanced pulmonary bacterial clearance of all three serotypes of M. catarrhalis strains in vaccinated mice, but also elevated serotype-specific anti-LOS immunoglobulin (IgA and IgG titers in nasal wash and serum respectively. Mice vaccinated with the combined LOS conjugates also showed increased interferon (IFN-γ, interleukin (IL-12, and IL-4 in the lungs after challenges. Compared to the control group, mice immunized with the combined LOS conjugates also showed reduced lung inflammation after M. catarrhalis infections. The hyperimmune sera induced by the combined conjugates exhibited a broad cross-reactivity toward all three serotypes of M. catarrhalis under transmission electron microscopy.The combined vaccine of serotype A and B LOS conjugates provides protection against most M. catarrhalis strains by eliciting humoral and cellular immune responses.

  10. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

    Science.gov (United States)

    Daughters, Katie; Manstead, Antony S R; Hubble, Kelly; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H M

    2015-01-01

    The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

  11. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

    Directory of Open Access Journals (Sweden)

    Katie Daughters

    Full Text Available The use of intranasal oxytocin (OT in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

  12. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    Science.gov (United States)

    Harmon, Brendan Trevor

    -of-principle study with pCG, a new plasmid was created by Copernicus Therapeutics, Inc. to better mimic their long-lasting pGDNF plasmid while providing both GDNF as well as the reporter function of eGFP. This eGFP-GDNF plasmid was used to monitor expression and cell-types transfected. This expression plasmid, called pUGG, was first characterized in vitro to verify protein expression. Transfection experiments in SHEP-1 neuroblastoma cells, ventral midbrain cultures, and N27 dopaminergic cells all demonstrated that pUGG expressed bioactive eGFP and GDNF. However, cleavage of the two proteins did not occur and the expressed protein emerged as a fusion construct which was not detectable by GDNF-ELISA, although it was detected by GFP-ELISA. The next goal was to determine if pUGG was able to transfect cells in vivo in rat brain. Direct striatal injection of pUGG nanoparticles showed significant eGFP expression at the site of injection both 7 and 14 days post-administration with no difference in eGFP expression between the two time-points. GFP-immunohistochemistry at the striatal injection site revealed expression of eGFP-positive cells as well as evidence of GDNF's bioactivity as indicated by neurite outgrowth. Moving forward, we administered pUGG nanoparticles intranasally to rats and found significant expression seven days later throughout the brain, with highest levels in the forebrain areas (olfactory bulb and frontal cortex). Significant expression was also seen along the rostral-caudal axis of the brain compared with naked pUGG plasmid. The final goal of this work was to examine whether intranasal pGDNF pre-treatment could generate sufficient GDNF to protect SN dopamine neurons after a unilateral 6-hydroxydopmaine (6-OHDA) lesion, a common animal model for PD. Copernicus' pGDNF plasmid was utilized for the neuroprotection experiments to avoid possible confounds due to the GFP fusion produced by pUGG. Tyrosine hydroxylase-immunostaining density was used as a marker for dopamine

  13. Comparison of intranasal azelastine to intranasal fluticasone propionate for symptom control in moderate-to-severe seasonal allergic rhinitis.

    Science.gov (United States)

    Carr, Warner W; Ratner, Paul; Munzel, Ullrich; Murray, Ruth; Price, David; Canonica, G Walter; Mullol, Joaquim; Virchow, J Christian; Lieberman, Phil; Meltzer, Eli; Bachert, Claus

    2012-01-01

    Intranasal corticosteroids are considered the most effective therapy for moderate-to-severe seasonal allergic rhinitis (SAR) and recommended first line in guidelines. It is uncertain whether intranasal antihistamines have comparable efficacy. This study was designed to compare the efficacy of azelastine (AZE; 137 μg/spray) and fluticasone propionate (FP; 50 μg/spray), both given as 1 spray/nostril bid (i.e., approved dosing regimen in the United States), in SAR via a post hoc analysis of data from a previously published direct-comparison study. Six hundred ten moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, parallel-group trial. The primary efficacy variable was change from baseline in reflective total nasal symptom score (rTNSS (morning and evening), over 14 days. Reflective total ocular symptom score (rTOSS) was a key secondary variable. Reflective total of seven symptom scores (rT7SS [nasal plus ocular symptoms]) and time to ≥50% reduction from baseline in these key parameters were also analyzed. AZE and FP reduced rTNSS from baseline by a similar degree (-3.25 versus -3.84; p = 0.2014). Patients experienced comparable improvement in rTOSS (-2.62 versus -2.17; p = 0.2371) and rT7SS (-5.83 versus -6.05; p = 0.7820). FP was superior to AZE in alleviating rhinorrhea (-1.15 versus -0.87; p = 0.0433), but AZE showed comparable efficacy for all other nasal and ocular symptoms. There was no clinically or statistically significant difference between AZE (-1.17) and FP (-1.43) for reduction in the overall rhinitis quality of life questionnaire score (although FP, but not AZE, significantly differed from placebo). A similar proportion of patients in the AZE and FP groups achieved a 50% reduction in rTNSS. However, more AZE patients (53.0%) exhibited a 50% reduction in rTOSS by day 14 versus FP (39.6%), and ≤3 days faster (p = 0.028). Intranasal AZE (137 micrograms/spray) and intranasal FP (50 micrograms

  14. Decrease in Anti-HBs Antibodies over Time in Medical Students and Healthcare Workers after Hepatitis B Vaccination

    Directory of Open Access Journals (Sweden)

    H. V. Sahana

    2017-01-01

    Full Text Available Background. Hepatitis B is one of the most important occupational hazards among healthcare workers (HCWs. This study aimed to measure the anti-HBs titres among the medical students and HCWs vaccinated against hepatitis B virus and to determine the association between anti-HBs levels and time since vaccination. Materials and Methods. In this cross-sectional study, medical students and healthcare workers who had received all three doses of hepatitis B vaccination and completed at least six months after vaccination since the last dose were included. 3 ml blood was collected from subjects (n=340 and anti-HBs titre was estimated using ELISA. Results. A total of 340/400 subjects were aged between 18 and 60 years; 204 were females and 136 males. The median and interquartile range for time since vaccination were 5 and 5 years, respectively. Duration since vaccination was ≤5 years in 223 (65.5%, 6–10 years in 84 (24.7%, and >10 years in 33 (9.70%; among them, antibody titres were >10 mIU/ml in 94.1%, 79.7%, and 72.7% subjects, respectively. There was significant decline in antibody titres as duration of postvaccination increased. Conclusion. The proportion of subjects who were unprotected after 5 and 10 years after vaccination were 20% and 27%, respectively. The need for a booster dose can be made mandatory at least for healthcare professionals.

  15. Use of intranasal corticosteroids in adenotonsillar hypertrophy.

    Science.gov (United States)

    Sakarya, E U; Bayar Muluk, N; Sakalar, E G; Senturk, M; Aricigil, M; Bafaqeeh, S A; Cingi, C

    2017-05-01

    This review examined the efficacy of intranasal corticosteroids for improving adenotonsillar hypertrophy. The related literature was searched using PubMed and Proquest Central databases. Adenotonsillar hypertrophy causes mouth breathing, nasal congestion, hyponasal speech, snoring, obstructive sleep apnoea, chronic sinusitis and recurrent otitis media. Adenoidal hypertrophy results in the obstruction of nasal passages and Eustachian tubes, and blocks the clearance of nasal mucus. Adenotonsillar hypertrophy and obstructive sleep apnoea are associated with increased expression of various mediators of inflammatory responses in the tonsils, and respond to anti-inflammatory agents such as corticosteroids. Topical nasal steroids most likely affect the anatomical component by decreasing inspiratory upper airway resistance at the nasal, adenoidal or tonsillar levels. Corticosteroids, by their lympholytic or anti-inflammatory effects, might reduce adenotonsillar hypertrophy. Intranasal corticosteroids reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil and adenoid mixed-cell culture system. Intranasal corticosteroids have been used in adenoidal hypertrophy and adenotonsillar hypertrophy patients, decreasing rates of surgery for adenotonsillar hypertrophy.

  16. Evaluation of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer nanomicelle for trigeminal ganglion neurons delivering with intranasal administration.

    Science.gov (United States)

    Li, Mengshuang; Xin, Meng; Song, Kaichao; Sun, Fengyuan; Hou, Yuzhen; Li, Jun; Wu, Xianggen

    2018-03-01

    Purpose How to deliver enough medical agents to the trigeminal ganglion (TG) neurons conveniently still remains a challenge in pharmaceutics and clinics. The purpose of this study was to reveal that intranasal administration of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG) nanomicelle formulation could efficiently deliver agent to TG neurons in mice. Methods Ocular topical or intranasal administration of nanomicelle coumarin-6 was performed in mice, and tissue distribution after administration (0.25, 1, 2, 4, 6, 8, and 10 h) was analyzed. Fluoro-Gold was used as a retrograde tracer to identify corneal and nasal neurons in the TG. Pharmacokinetic profiles after ocular topical or intranasal administration were explored in detail. Results Coumarin-6 levels in the TG neurons were significantly higher in intranasal administration groups than in topical administration groups, and the difference was statistically significant (P < 0.05) at all time points except for 10 h. Interestingly, in cornea, coumarin-6 was detected after intranasal administration. For intranasal administration groups, it was also interestingly found that coumarin-6 levels in the TG neurons were much higher than that in the brain, suggesting that the TG neurons was a target tissue after the intranasal administration of nanomicelle coumarin-6. These levels also indicated the safety of brain tissue after intranasal administration. Using Fluoro-Gold tract tracing techniques, coumarin-6 was detected in TG neurons after either ocular topical or intranasal administration of nanomicelle coumarin-6, indicating the high colocalization of corneal and nasal neurons in the TG. Conclusions Intranasal administration of PVCL-PVA-PEG nanomicelle formulation could efficiently deliver to TG neurons, and it might be a promising therapy for pathological TG neurons.

  17. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

    Directory of Open Access Journals (Sweden)

    Shana P C Barroso

    Full Text Available Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling. Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  18. Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45

    Directory of Open Access Journals (Sweden)

    Michael Pritsch

    2016-01-01

    Full Text Available Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3 were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 105 could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases.

  19. Transethmoidal intranasal meningoencephalocele in an adult with recurrent meningitis.

    Science.gov (United States)

    Hasegawa, Takafumi; Sugeno, Naoto; Shiga, Yusei; Takeda, Atsushi; Karibe, Hiroshi; Tominaga, Teiji; Itoyama, Yasuto

    2005-08-01

    Intranasal meningoencephalocele is a rarely encountered congenital malformation. We report a case of transethmoidal intranasal meningoencephalocele in a 52-year old man with recurrent purulent meningitis. After treatment of the acute meningitis, frontal craniotomy followed by the removal of the stalk of the meningoencephalocele and repair of the bony defect was successfully performed. He has had no further meningitis or CSF rhinorrhea post-operatively. Detailed neuroradiological examination and appropriate surgical treatment are important to prevent fatal neurological complications of intranasal meningoencephalocele.

  20. Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, J C; Madsbad, S; Rasmussen, M H

    1996-01-01

    Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...... subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment...

  1. Influenza (Flu) vaccine (Live, Intranasal): What you need to know

    Science.gov (United States)

    ... nose. LAIV does not contain thimerosal or other preservatives. It is made from weakened flu virus and ... people should not get LAIV because of age, health conditions, or other reasons. Most of these people ...

  2. Influenza vaccines: Evaluation of the safety profile

    Science.gov (United States)

    Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele

    2018-01-01

    ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746

  3. Time will tell: community acceptability of HIV vaccine research before and after the “Step Study” vaccine discontinuation

    Directory of Open Access Journals (Sweden)

    Paula M Frew

    2010-09-01

    Full Text Available Paula M Frew1,2,3,4, Mark J Mulligan1,2,3, Su-I Hou5, Kayshin Chan3, Carlos del Rio1,2,3,61Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA; 2Emory Center for AIDS Research, Atlanta, Georgia, USA; 3The Hope Clinic of the Emory Vaccine Center, Decatur, Georgia, USA; 4Department of Behavioral Sciences and Health Education, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; 5Department of Health Promotion and Behavior, College of Public Health, University of Georgia, Athens, Georgia, USA; 6Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USAObjective: This study examines whether men-who-have-sex-with-men (MSM and transgender (TG persons’ attitudes, beliefs, and risk perceptions toward human immunodeficiency virus (HIV vaccine research have been altered as a result of the negative findings from a phase 2B HIV vaccine study.Design: We conducted a cross-sectional survey among MSM and TG persons (N = 176 recruited from community settings in Atlanta from 2007 to 2008. The first group was recruited during an active phase 2B HIV vaccine trial in which a candidate vaccine was being evaluated (the “Step Study”, and the second group was recruited after product futility was widely reported in the media.Methods: Descriptive statistics, t tests, and chi-square tests were conducted to ascertain differences between the groups, and ordinal logistic regressions examined the influences of the above-mentioned factors on a critical outcome, future HIV vaccine study participation. The ordinal regression outcomes evaluated the influences on disinclination, neutrality, and inclination to study participation.Results: Behavioral outcomes such as future recruitment, event attendance, study promotion, and community mobilization did not reveal any differences in participants’ intentions between the groups. However, we observed

  4. Long-term exposure to intranasal oxytocin in a mouse autism model.

    Science.gov (United States)

    Bales, K L; Solomon, M; Jacob, S; Crawley, J N; Silverman, J L; Larke, R H; Sahagun, E; Puhger, K R; Pride, M C; Mendoza, S P

    2014-11-11

    Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8  IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.

  5. Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery.

    Science.gov (United States)

    Salatin, Sara; Barar, Jaleh; Barzegar-Jalali, Mohammad; Adibkia, Khosro; Milani, Mitra Alami; Jelvehgari, Mitra

    2016-09-01

    Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.

  6. Time-Series Adaptive Estimation of Vaccination Uptake Using Web Search Queries

    OpenAIRE

    Hansen, Niels Dalum; Mølbak, Kåre; Cox, Ingemar J.; Lioma, Christina

    2017-01-01

    Estimating vaccination uptake is an integral part of ensuring public health. It was recently shown that vaccination uptake can be estimated automatically from web data, instead of slowly collected clinical records or population surveys. All prior work in this area assumes that features of vaccination uptake collected from the web are temporally regular. We present the first ever method to remove this assumption from vaccination uptake estimation: our method dynamically adapts to temporal fluc...

  7. Dynamical analysis of rumor spreading model with impulse vaccination and time delay

    Science.gov (United States)

    Huo, Liang'an; Ma, Chenyang

    2017-04-01

    Rumor cause unnecessary conflicts and confusion by misleading the cognition of the public, its spreading has largely influence on human affairs. All kinds of rumors and people's suspicion are often caused by the lack of official information. Hence, the official should take a variety of channels to deny the rumors. The promotion of scientific knowledge is implemented to improve the quality of the whole nation, reduce the harm caused by rumor spreading. In this paper, regarding the process of the science education that official deny the rumor many times as periodic impulse, we propose a XWYZ rumor spreading model with impulse vaccination and time delay, and analyze the global dynamics behaviors of the model. By using the discrete dynamical system determined by the comparison theory and Floquet theorem, we show that there exists a rumor-free periodic solution. Further, we show that the rumor-free periodic solution is globally attractive under appropriate conditions. We also obtain a sufficient condition for the permanence of model. Finally, with the numerical simulation, our results indicate that large vaccination rate, short impulse period or long latent period is sufficient condition for the extinction of the rumors.

  8. CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

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    Olga Dal Monte

    Full Text Available Oxytocin (OT in the central nervous system (CNS influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline to 15 primates (Macaca mulatta, using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

  9. [Vaccination against hepatitis B. Impact of vaccination programmes after 20 years of use in Spain. Is it time for a change?].

    Science.gov (United States)

    Arístegui Fernández, Javier; Díez-Domingo, Javier; Marés Bermúdez, Josep; Martinón Torres, Federico

    2015-02-01

    The highest incidence rate of hepatitis B (HB) in Spain is detected in adults between 20 and 54 years old, whereas the incidence in children under 1 year old is almost nil. The low prevalence of HB in children under 1 year is mainly due to the success of gestational screening strategies for the detection of HBsAg(+) in pregnant women, and vaccination campaigns during childhood. Currently, in Spain, the last dose of the HB included in the national childhood immunization program is administered at 6 months of age, although some studies show that delaying the age of the administration of the last dose of HB vaccine and increasing the time between doses, may improve immune memory by offering greater protection against this virus in the adulthood. In this article, the impact of HB vaccination in Spain is reviewed, and other potential vaccination strategies in our environment are discussed, such as extending the interval between doses, and administering the last dose in the second year of life, adapting the valid strategy in Spain to the current epidemiological context in order to reduce the prevalence of HB in adulthood. Copyright © 2015. Published by Elsevier España.

  10. Deposition of intranasal glucocorticoids--preliminary study.

    Science.gov (United States)

    Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

    2015-01-01

    Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

  11. Development of real-time PCR to detect oral vaccine-like poliovirus and its application to environmental surveillance.

    Science.gov (United States)

    Iwai-Itamochi, Masae; Yoshida, Hiromu; Obara-Nagoya, Mayumi; Horimoto, Eiji; Kurata, Takeshi; Takizawa, Takenori

    2014-01-01

    In order to perform environmental surveillance to track oral poliovirus vaccine-like poliovirus sensitively and conveniently, real-time PCR was developed and applied to a raw sewage concentrate. The real-time PCR method detected 0.01-0.1 TCID50 of 3 serotypes of Sabin strain specifically. The method also detected the corresponding serotypes of oral poliovirus vaccine-like poliovirus specifically, but detected neither wild poliovirus, except Mahoney for type 1 and Saukett for type 3, nor other enteric viruses, as far as examined. When real-time PCR was applied to environmental surveillance, the overall agreement rates between real-time PCR and the cell culture were 83.3% for all serotypes. Since real-time PCR has the advantages of rapid detection of viruses and minimum requirement of sampling volume as compared with ordinary cell culture, it is suitable to monitor oral poliovirus vaccine-like poliovirus in the environment, especially in areas where an oral vaccine is being replaced by an inactivated vaccine. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Effects of Intranasal Oxytocin on the Interpretation and Expression of Emotions in Anorexia Nervosa.

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    Leppanen, J; Cardi, V; Ng, K W; Paloyelis, Y; Stein, D; Tchanturia, K; Treasure, J

    2017-03-01

    Altered social-emotional functioning is considered to play an important role in the development and maintenance of anorexia nervosa (AN). Recently, there has been increasing interest in investigating the role of intranasal oxytocin in social-emotional processing. The present study aimed to investigate the effects of intranasal oxytocin on the interpretation and expression of emotions among people with AN. Thirty women with AN and 29 age-matched healthy women took part in the present study, which used a double-blind, placebo-controlled, cross-over design. The participants received a single dose of 40 IU of intranasal oxytocin in one session and a placebo spray in the other. Fifteen minutes after administration, the participants completed the Reading the Mind in the Eyes Test to assess the interpretation of complex emotions and mental states followed by a video task, which assessed expressions of facial affect when they were viewing humorous and sad film clips. The intranasal oxytocin did not significantly influence the expression or interpretation of emotions in the AN or healthy comparison groups. The AN group expressed significantly less positive emotion, spent more time looking away and reported experiencing a significantly more negative affect in response to the film clips. The finding that intranasal oxytocin had little to no effect on the interpretation or expression of emotions in either group supports the notion that the effects of oxytocin on social-emotional processing are not straightforward and may depend on individual and environmental differences, as well as the emotion being processed. Replication of these findings is necessary to explore the effect of timing on the effects of oxytocin before firm conclusions can be drawn. Nonetheless, these findings add to the steady accumulation of evidence that people with AN have reduced emotional expression and avoidance of emotionally provoking stimuli. © 2017 The Authors. Journal of Neuroendocrinology

  13. Influence of anatomy and head position on intranasal drug deposition

    NARCIS (Netherlands)

    Merkus, Paul; Ebbens, Fenna A.; Muller, Barbara; Fokkens, Wytske J.

    2006-01-01

    The objective of this study was to determine the influence of individual anatomical differences on intranasal drug deposition. The data of a comparison of seven different administration techniques in ten healthy volunteers was used in this single-blind crossover pilot study. After intranasal

  14. Iatrogenic Cushing's syndrome following short-term intranasal steroid use.

    Science.gov (United States)

    Dutta, Deep; Shivaprasad, K S; Ghosh, Sujoy; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2012-09-01

    Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. In this paper, we present the case of a child who developed CS after intranasal application of combined moxifloxacin-dexamethasone eye drops for epistaxis for a period of 3 months. CS caused by ocular preparations of steroids has not been reported previously. This case report highlights the fact that even eye drops can contain high doses of steroids and can lead to CS especially in children and especially if used intranasally. Ocular steroid drops should not be used intranasally. To minimize gastrointestinal absorption and therefore the risk of CS, nasal sprays should be preferred over nasal drops for intranasal steroid application.

  15. Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

    Directory of Open Access Journals (Sweden)

    Joseph Prescott

    2014-01-01

    Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

  16. Vaccination against 2009 pandemic H1N1 in a population dynamical model of Vancouver, Canada: timing is everything

    Science.gov (United States)

    2011-01-01

    Background Much remains unknown about the effect of timing and prioritization of vaccination against pandemic (pH1N1) 2009 virus on health outcomes. We adapted a city-level contact network model to study different campaigns on influenza morbidity and mortality. Methods We modeled different distribution strategies initiated between July and November 2009 using a compartmental epidemic model that includes age structure and transmission network dynamics. The model represents the Greater Vancouver Regional District, a major North American city and surrounding suburbs with a population of 2 million, and is parameterized using data from the British Columbia Ministry of Health, published studies, and expert opinion. Outcomes are expressed as the number of infections and deaths averted due to vaccination. Results The model output was consistent with provincial surveillance data. Assuming a basic reproduction number = 1.4, an 8-week vaccination campaign initiated 2 weeks before the epidemic onset reduced morbidity and mortality by 79-91% and 80-87%, respectively, compared to no vaccination. Prioritizing children and parents for vaccination may have reduced transmission compared to actual practice, but the mortality benefit of this strategy appears highly sensitive to campaign timing. Modeling the actual late October start date resulted in modest reductions in morbidity and mortality (13-25% and 16-20%, respectively) with little variation by prioritization scheme. Conclusion Delays in vaccine production due to technological or logistical barriers may reduce potential benefits of vaccination for pandemic influenza, and these temporal effects can outweigh any additional theoretical benefits from population targeting. Careful modeling may provide decision makers with estimates of these effects before the epidemic peak to guide production goals and inform policy. Integration of real-time surveillance data with mathematical models holds the promise of enabling public health

  17. Conditioned social preference, but not place preference, produced by intranasal oxytocin in female mice.

    Science.gov (United States)

    Kosaki, Yutaka; Watanabe, Shigeru

    2016-04-01

    Oxytocin (OT) has been implicated in a variety of mammalian reproductive and social behaviors, and the use of intranasal OT for clinical purposes is on the rise. However, basic actions of OT, including the rewarding or reinforcing properties of the drug, are currently not fully understood. In this study, the authors investigated whether intranasally administered OT has different reinforcing properties for social and nonsocial stimuli and whether such effects are variable between male and female subjects. Conditioned social preference (CSP) and conditioned place preference (CPP) paradigms were used to examine social and nonsocial reinforcing properties of OT. In CSP, the presence of a same-sex unfamiliar conspecific was repeatedly paired with intranasal OT, while a different conspecific was associated with saline. The reinforcing effect of OT was assessed in a postconditioning choice test under a drug-free condition. In CPP, the 2 conspecifics were replaced with nonsocial black and white compartments. The authors found that intranasal OT (12 μg) in females supported the formation of CSP (Experiment 1) but not CPP (Experiment 3). Neither CSP (Experiment 2) nor CPP (Experiment 4) was formed in males. Extended conditioning with higher dose OT (36 μg), however, abolished the initial CSP in females and produced an aversion to the OT-paired stimulus mouse. Experiment 5 indicated that it was the repeated administrations rather than the higher dose that produced the abolition of the original preference. Overall, the current results demonstrate for the first time a sex- and stimulus-dependent reinforcing property of intranasal OT in mice. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection against Naegleria fowleri Meningoencephalitis

    Science.gov (United States)

    Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A.; López-Revilla, Rubén; Reséndiz-Albor, Aldo A.; Moreno-Fierros, Leticia

    2004-01-01

    Cry1Ac protoxin has potent mucosal and systemic adjuvant effects on antibody responses to proteins or polysaccharides. In this work, we examined whether Cry1Ac increased protective immunity against fatal Naegleria fowleri infection in mice, which resembles human primary amoebic meningoencephalitis. Higher immunoglobulin G (IgG) than IgA anti-N. fowleri responses were elicited in the serum and tracheopulmonary fluids of mice immunized by the intranasal or intraperitoneal route with N. fowleri lysates either alone or with Cry1Ac or cholera toxin. Superior protection against a lethal challenge with 5 × 104 live N. fowleri trophozoites was achieved for immunization by the intranasal route. Intranasal immunization of N. fowleri lysates coadministered with Cry1Ac increased survival to 100%; interestingly, immunization with Cry1Ac alone conferred similar protection to that achieved with amoebal lysates alone (60%). When mice intranasally immunized with Cry1Ac plus lysates were challenged with amoebae, both IgG and IgA mucosal responses were rapidly increased, but only the increased IgG response persisted until day 60 in surviving mice. The brief rise in the level of specific mucosal IgA does not exclude the role that this isotype may play in the early defense against this parasite, since higher IgA responses were detected in nasal fluids of mice intranasally immunized with lysates plus either Cry1Ac or cholera toxin, which, indeed, were the treatments that provided the major protection levels. In contrast, serum antibody responses do not seem to be related to the protection level achieved. Both acquired and innate immune systems seem to play a role in host defense against N. fowleri infection, but further studies are required to elucidate the mechanisms involved in protective effects conferred by Cry1Ac, which may be a valuable tool to improve mucosal vaccines. PMID:15271892

  19. Vaccination and timing influence SIV immune escape viral dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Liyen Loh

    2008-01-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTL can be effective at controlling HIV-1 in humans and SIV in macaques, but their utility is partly offset by mutational escape. The kinetics of CTL escape and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help us understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. Traditional methods for following CTL escape and reversion are, however, insensitive to minor viral quasispecies. We developed sensitive quantitative real-time PCR assays to track the viral load of SIV Gag164-172 KP9 wild-type (WT and escape mutant (EM variants in pigtail macaques. Rapid outgrowth of EM virus occurs during the first few weeks of infection. However, the rate of escape plateaued soon after, revealing a prolonged persistence of WT viremia not detectable by standard cloning and sequencing methods. The rate of escape of KP9 correlated with levels of vaccine-primed KP9-specific CD8+ T cells present at that time. Similarly, when non-KP9 responder (lacking the restricting Mane-A*10 allele macaques were infected with SHIVmn229 stock containing a mixture of EM and WT virus, rapid reversion to WT was observed over the first 2 weeks following infection. However, the rate of reversion to WT slowed dramatically over the first month of infection. The serial quantitation of escape mutant viruses evolving during SIV infection shows that rapid dynamics of immune escape and reversion can be observed in early infection, particularly when CD8 T cells are primed by vaccination. However, these early rapid rates of escape and reversion are transient and followed by a significant slowing in these rates later during infection, highlighting that the rate of escape is significantly influenced by the timing of its occurrence.

  20. Fluticasone furoate: A new intranasal corticosteroid

    Directory of Open Access Journals (Sweden)

    R Kumar

    2012-01-01

    Full Text Available Intranasal corticosteroids are recommended as one of the first-line therapies for the treatment of allergic rhinitis (AR, especially when associated with nasal congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of AR approved by the Food and Drug Administration in 2007 and recently introduced in India. Fluticasone furoate nasal spray is indicated for the treatment of the symptoms of seasonal and perennial AR in patients aged two years and older. This review summarizes the clinical data on fluticasone furoate nasal spray and discusses its role in the management of AR. Important attributes of fluticasone furoate include low systemic bioavailability (<0.5%, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these properties, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance, thus making it a good choice amongst available intranasal steroids.

  1. Contraceptive Vaccines

    Directory of Open Access Journals (Sweden)

    M.V. Supotnitsky

    2014-02-01

    Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the

  2. Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Mans, Christoph; Guzman, David Sanchez-Migallon; Lahner, Lesanna L; Paul-Murphy, Joanne; Sladky, Kurt K

    2012-09-01

    Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and effects on cloacal temperature, respiratory rate, and heart rate in manually restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9) were administered either midazolam (2 mg/kg) or an equal volume of saline solution intranasally before a 15-minute manual restraint in a complete crossover study. Respiratory rate and sedation scores were recorded before and during capture and during and after 15 minutes of manual restraint. Heart rate and cloacal temperature were recorded during manual restraint. After restraint, the parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline solution, and the recovery time was recorded. In those birds that received midazolam, sedation was observed within 3 minutes of administration, and vocalization, flight, and defense responses were significantly reduced during capture. During manual restraint, the mean rate of cloacal temperature increase was significantly slower and remained significantly lower in birds that received midazolam compared with controls. Mean respiratory rates were significantly lower for up to 12 minutes in parrots that received midazolam compared with those receiving saline solution. Flumazenil antagonized the effects of midazolam within 10 minutes. No overt clinical adverse effects to intranasal midazolam and flumazenil administration were observed. Further studies on the safety of intranasal midazolam and flumazenil in this species are warranted.

  3. Determination of the optimal time of vaccination against infectious bursal disease virus (Gumboro) in Algeria.

    Science.gov (United States)

    Besseboua, Omar; Ayad, Abdelhanine; Benbarek, Hama

    2015-04-30

    This study was conducted to determine the effect of maternally derived antibody (MDA) on live vaccine against infectious bursal disease. A total of 140 chicks selected from vaccinated parent stock were used in this investigation. In a preset vaccination schedule, blood samples were collected to check for the actual effect. It was noticed that on day 1 the chicks contained a high level (6400.54 ± 2993.67) of maternally derived antibody that gradually decreased below a positive level within 21 days (365.86 ± 634.46). It was found that a high level of MDA interferes with the vaccine virus, resulting in no immune response. For better immune response, it is suggested that the chickens should be vaccinated at day 21, as the uniformity of MDA is poor (coefficient of the variation [CV] > 30%), and boosted at day 28. Indeed, two vaccinations are necessary to achieve good protection against infectious bursal disease virus of the entire flock.

  4. Acceptability of Aujeszky's disease vaccines.

    Science.gov (United States)

    Kimman, T G

    1992-01-01

    Vaccines against Aujeszky's disease are not only used to prevent the clinical consequences of a field infection, but also to support eradication of the virus. The current Aujeszky's disease vaccines (ADV) protect against severe clinical signs of disease and they reduce but usually do not prevent virus multiplication and excretion or the establishment of latency after infection. Vaccines also limit virus multiplication after reactivation. The efficacy of vaccination is reduced by passively acquired maternal antibodies. The mechanisms that afford immunity to the virus are only poorly understood. No simple parameters for immunity are therefore available. The European Pharmacopoeia formulates requirements for inactivated and live ADV vaccines for parenteral use. The vaccines must be safe; they must not induce local or systemic reactions; they must not be transmitted to unvaccinated pigs; they must not be transmitted by semen and across the placenta; the attenuation must be irreversible (live vaccines); the inactivation must be complete (inactivated vaccines); they must prevent mortality and limit growth retardation after challenge infection; the vaccine must not contain contaminating micro-organisms and viruses. No requirements have been formulated with regard to reduction of excretion of challenge virus after experimental infection, efficacy in pigs with maternal antibodies, reproducibility of efficacy studies, reduction of virus transmission under field conditions, the presence of a serological marker, safety for other species, and safety and efficacy of intranasally administered vaccines. Future developments should be directed to the development and evaluation of ADV vaccines that are able to limit transmission of the virus.

  5. Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

    Directory of Open Access Journals (Sweden)

    Savannah E. Howe

    2016-10-01

    Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

  6. Intranasal oxytocin blocks alcohol withdrawal in human subjects.

    Science.gov (United States)

    Pedersen, Cort A; Smedley, Kelly L; Leserman, Jane; Jarskog, Lars Fredrik; Rau, Shane W; Kampov-Polevoi, Alexei; Casey, Robin L; Fender, Trace; Garbutt, James C

    2013-03-01

    The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients. Copyright © 2012 by the Research Society on Alcoholism.

  7. Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine.

    Science.gov (United States)

    Ott, J

    2001-01-01

    Summarized are psychonautic bioassays (human self-experiments) of pharmepéna--crystalline 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-Me-bufotenine), at times combined with crystalline beta-carbolines (harmaline or harmine). These substances were administered via intranasal, sublingual and oral routes, by way of pharmacological modeling of diverse South American shamanic inebriants (principally the snuffs epéna/nyakwana, prepared from barks of diverse species of Virola.) Intranasal, sublingual and oral psychoactivity of 5-MeO-DMT, and the 1967 Holmstedt-Lindgren hypothesis of the paricá-effect--intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs--have been confirmed by some 17 psychonautic bioassays. Salient phytochemical and psychonautic literature is reviewed.

  8. HIV vaccine: it may take two to tango, but no party time yet

    NARCIS (Netherlands)

    Berkhout, B.; Paxton, W.A.

    2009-01-01

    ABSTRACT: A press conference on Thursday September 24 in Bangkok, Thailand, released data that an experimental vaccine provided mild protection against HIV-1 infection. This is the first positive signal of any degree of vaccine efficacy in humans, more than a quarter-century after scientists

  9. Optimal Allocation of Pandemic Influenza Vaccine Depends on Age, Risk and Timing

    NARCIS (Netherlands)

    Mylius, S.D.; Hagenaars, T.H.J.; Lugner, A.K.; Wallinga, J.

    2008-01-01

    The limited production capacity for vaccines raises the question what the best strategy is for allocating the vaccine to mitigate an influenza pandemic. We developed an age-structured model for spread of an influenza pandemic and validated it against observations from the Asian flu pandemic. Two

  10. Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

    Science.gov (United States)

    Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.

    2015-01-01

    Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. PMID:26343192

  11. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

    vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...... respond to vaccination by increasing the specific antibody titer and by activating the cellular responses. My talk will cover vaccination methods in fish, immune responses and some adverse effect of oil-adjuvanted vaccines in fish with reference to our work in rainbow trout, Oncorhynchus mykiss....

  12. Extended Follow-up Confirms Early Vaccine-Enhanced Risk of HIV Acquisition and Demonstrates Waning Effect Over Time Among Participants in a Randomized Trial of Recombinant Adenovirus HIV Vaccine (Step Study)

    Science.gov (United States)

    Duerr, Ann; Huang, Yunda; Buchbinder, Susan; Coombs, Robert W.; Sanchez, Jorge; del Rio, Carlos; Casapia, Martin; Santiago, Steven; Gilbert, Peter; Corey, Lawrence; Robertson, Michael N.

    2012-01-01

    Background. The Step Study tested whether an adenovirus serotype 5 (Ad5)–vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. Methods. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. Results. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03–1.92; P = .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P = 1.0) over all follow-up time. Conclusions. The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination. Clinical Trials Registration. NCT00095576. PMID:22561365

  13. The cardiovascular effects and pharmacokinetics of intranasal tetracaine plus oxymetazoline: preliminary findings.

    Science.gov (United States)

    Giannakopoulos, Helen; Levin, Lawrence M; Chou, Joli C; Cacek, Anthony T; Hutcheson, Matthew; Secreto, Stacey A; Moore, Paul A; Hersh, Elliot V

    2012-08-01

    The authors evaluated the cardiovascular effects and pharmacokinetics of an intranasal 3 percent tetracaine/0.05 percent oxymetazoline spray developed to provide needle-free anesthesia of maxillary teeth. The authors administered to 12 participants a proposed maximum recommended dose (MRD) (18 milligrams tetracaine/0.3 mg oxymetazoline) as three bilateral pairs of 0.1-milliliter nasal sprays. They administered two times this dose (36 mg tetracaine/0.6 mg oxymetazoline) as six bilateral pairs one to three weeks later. The authors recorded the patients' heart rate, blood pressure and oxygen saturation. They drew blood samples at baseline and 15 times during the two hours after drug administration. Physiological measures remained fairly stable throughout the two-hour period, with small but significant decreases (P Oxymetazoline concentrations from the two-times-MRD administration were approximately 50 percent greater than those from the MRD administration, with a half-life of 1.72 to 2.32 hours. Intranasal tetracaine/oxymetazoline mist generally was well tolerated in study participants. The safety profile and pharmacokinetics of this intranasal formulation indicate that it appears to be generally well tolerated in patients for achieving anesthesia of the maxilla. Additional safety and efficacy data are required, particularly in patients with cardiovascular disease and other comorbidities.

  14. Intranasal insulin in Alzheimer's disease: Food for thought.

    Science.gov (United States)

    Chapman, Colin D; Schiöth, Helgi B; Grillo, Claudia A; Benedict, Christian

    2017-11-24

    Accumulating evidence suggests that disrupted brain insulin signaling promotes the development and progression of Alzheimer's disease (AD), driving clinicians to target this circuitry. While both traditional and more modern antidiabetics show promise in combating insulin resistance, intranasal insulin appears to be the most efficient method of boosting brain insulin. Furthermore, intranasal delivery elegantly avoids adverse effects from peripheral insulin administration. However, there remain significant open questions regarding intranasal insulin's efficacy, safety, and potential as an adjunct or mono-therapy. Thus, this review aims to critically evaluate the present evidence and future potential of intranasal insulin as a meaningful treatment for AD. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Diffusion of Pharmacy-Based Influenza Vaccination Over Time in the United States.

    Science.gov (United States)

    Chun, Grace J; Sautter, Jessica M; Patterson, Brandon J; McGhan, William F

    2016-06-01

    To examine pharmacy-based influenza vaccination using diffusion of innovation theory. We used 1993 to 2013 Behavioral Risk Factor Surveillance System data to generate weighted prevalence rates of influenza vaccination, stratified by age (18-64 years vs ≥ 65 years) and state of residence. The diffusion of innovation theory adopter categories were residents of states allowing pharmacist vaccination before 1996 ("innovator/early adopters"), between 1996 and 1998 ("early majority"), between 1999 and 2004 ("late majority"), and in 2007 or later ("laggards"). For adults aged 18 to 64 years, vaccination rates were similar before the innovation (1993), diverged as the innovation reached the majority (2003), and were significantly lower for laggard states by 2013. Younger adults' vaccination rates steadily increased from 12% to 16% in 1993 to 29% to 36% in 2013. For older adults, there was no significant difference in vaccination rates between adopter categories in any year and no advantage associated with adoption category. Key features of pharmacy-based vaccination, including relative advantage and compatibility, are most relevant to younger adults; different interventions are warranted for older adults.

  16. Efficacy of Fostera® PRRS modified live virus (MLV) vaccination strategy against a Thai highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection.

    Science.gov (United States)

    Charoenchanikran, Ponlakrit; Kedkovid, Roongtham; Sirisereewan, Chaitawat; Woonwong, Yonlayong; Arunorat, Jirapat; Sitthichareonchai, Panchan; Sopipan, Natthawan; Jittimanee, Suphattra; Kesdangsakonwut, Sawang; Thanawongnuwech, Roongroje

    2016-10-01

    Recently, the Chinese highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) (HP-PRRSV) belonging to lineage 8 causes severe symptom with high morbidity and high mortality rates to the Asian pig industry. A recent study showed that pigs immunized with Fostera® PRRS modified live virus (MLV) of lineage 8 could provide a degree of protection against a Vietnamese HP-PRRSV infection. It should be noted that PRRSV commonly found after weaning causes porcine respiratory disease complex (PRDC). Vaccination strategy should be evaluated in each farm scenario. Eighty-one PRRSV-free piglets obtained from a PRRS-free herd were divided into two experiments with the major difference of infection timing after vaccination, 42 days in experiment 1 (n = 42) and 28 days in experiment 2 (n = 39). Each experiment had similar protocol containing three groups including a negative control, unvaccinated challenged, and vaccinated challenged groups. Pigs in vaccination groups were immunized with Fostera® PRRS MLV vaccine at 3 weeks of age. Then, unvaccinated challenged and vaccinated challenged groups were intranasally inoculated with a Thai HP-PRRSV (10PL01). Vaccinated challenged pigs showed significantly lower levels of mean rectal temperatures, clinical severity, lung lesion scores, and viral titers in serum and lung tissue compared to the unvaccinated challenged pigs (p HP-PRRSV infection in both 42- and 28-day vaccination-to-infection protocols.

  17. Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection.

    Science.gov (United States)

    de Swart, Rik L; de Vries, Rory D; Rennick, Linda J; van Amerongen, Geert; McQuaid, Stephen; Verburgh, R Joyce; Yüksel, Selma; de Jong, Alwin; Lemon, Ken; Nguyen, D Tien; Ludlow, Martin; Osterhaus, Albert D M E; Duprex, W Paul

    2017-01-01

    Needle-free measles virus vaccination by aerosol inhalation has many potential benefits. The current standard route of vaccination is subcutaneous injection, whereas measles virus is an airborne pathogen. However, the target cells that support replication of live-attenuated measles virus vaccines in the respiratory tract are largely unknown. The aims of this study were to assess the in vivo tropism of live-attenuated measles virus and determine whether respiratory measles virus vaccination should target the upper or lower respiratory tract. Four groups of twelve cynomolgus macaques were immunized with 10 4 TCID 50 of recombinant measles virus vaccine strain Edmonston-Zagreb expressing enhanced green fluorescent protein. The vaccine virus was grown in MRC-5 cells and formulated with identical stabilizers and excipients as used in the commercial MV EZ vaccine produced by the Serum Institute of India. Animals were immunized by hypodermic injection, intra-tracheal inoculation, intra-nasal instillation, or aerosol inhalation. In each group six animals were euthanized at early time points post-vaccination, whereas the other six were followed for 14 months to assess immunogenicity and protection from challenge infection with wild-type measles virus. At early time-points, enhanced green fluorescent protein-positive measles virus-infected cells were detected locally in the muscle, nasal tissues, lungs, and draining lymph nodes. Systemic vaccine virus replication and viremia were virtually absent. Infected macrophages, dendritic cells and tissue-resident lymphocytes predominated. Exclusive delivery of vaccine virus to the lower respiratory tract resulted in highest immunogenicity and protection. This study sheds light on the tropism of a live-attenuated measles virus vaccine and identifies the alveolar spaces as the optimal site for respiratory delivery of measles virus vaccine.

  18. The role of co-spray-drying procedure in the preformulation of intranasal propranolol hydrochloride.

    Science.gov (United States)

    Ambrus, Rita; Gergely, Matild; Zvonar, Alenka; Szabó-Révész, Piroska; Sipos, Emese

    2014-01-01

    The use of dry powder formulations presents an alternative through which to achieve better deposition and residence time in the nasal cavity, increased stability and possible absorption enhancement. The most important factors involved in the preformulation are particle size and physical stability. Propranolol hydrochloride a model drug was subjected to spray-drying technology to form an intranasal dry powder. Particle size reduction of the drug was carried out by integration (spray-drying) methods, using different excipients. The micrometric properties were characterized by size and morphology. The structure was determined through the use of differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy investigations. It was concluded that the intranasal dry powder formulation of propranolol hydrochloride can be achieved with a suitable particle size without polymorph modification or chemical decomposition.

  19. Answering human papillomavirus vaccine concerns; a matter of science and time.

    Science.gov (United States)

    Hawkes, David; Lea, Candice E; Berryman, Matthew J

    2013-06-12

    Since the introduction of the HPV vaccine, questions have been asked about its efficacy in preventing cancer linked with HPV. Concerns about the HPV vaccine safety profile have also been raised. This paper highlights the rapidly growing body of evidence (including clinical trials and post-marketing surveillance) illustrating both the safety of the HPV vaccine, through a detailed investigation of reported adverse events, and its efficacy in reducing both HPV infections rates and the resulting drop in cervical lesions, which have been demonstrated to be good predictors of cervical cancer risk.

  20. Evaluation of vaccination herd immunity effects for anogenital warts in a low coverage setting with human papillomavirus vaccine-an interrupted time series analysis from 2005 to 2010 using health insurance data.

    Science.gov (United States)

    Thöne, Kathrin; Horn, Johannes; Mikolajczyk, Rafael

    2017-08-14

    Shortly after the human papillomavirus (HPV) vaccine recommendation and hence the reimbursement of vaccination costs for the respective age groups in Germany in 2007, changes in the incidence of anogenital warts (AGWs) were observed, but it was not clear at what level the incidence would stabilize and to what extent herd immunity would be present. Given the relatively low HPV vaccination coverage in Germany, we aimed to assess potential vaccination herd immunity effects in the German setting. A retrospective open cohort study with data from more than nine million statutory health insurance members from 2005 to 2010 was conducted. AGW cases were identified using ICD-10-codes. The incidence of AGWs was estimated by age, sex, and calendar quarter. Age and sex specific incidence rate ratios were estimated comparing the years 2009-2010 (post-vaccination period) with 2005-2007 (pre-vaccination period). Incidence rate ratio of AGWs for the post-vaccination period compared to the pre-vaccination period showed a u-shaped decrease among the 14- to 24-year-old females and males which corresponds well with the reported HPV vaccination uptake in 2008. A maximum reduction of up to 60% was observed for the 16- to 20-year-old females and slightly less pronounced (up to 50%) for the 16- and 18-year-old males. Age groups outside of the range 14-24 years demonstrated no decrease. The decrease of incidence occurred in both sexes early after the vaccine recommendation and stabilized at lower levels in 2009-2010. A relative reduction of up to 50% among males of approximately similar age groups as that of females receiving the HPV vaccination suggests herd protection resulting from assortative mixing by age. The early decrease among males can be reduced over time due to partner change.

  1. Absorption of clonazepam after intranasal and buccal administration.

    Science.gov (United States)

    Schols-Hendriks, M W; Lohman, J J; Janknegt, R; Korten, J J; Merkus, F W; Hooymans, P M

    1995-01-01

    Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1 was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that intranasal clonazepam is an alternative to buccal administration. However, the Cmax of clonazepam after intranasal administration is not high enough to recommend the intranasal route as an alternative to intravenous injection. PMID:7640154

  2. Non-clinical safety evaluation of intranasal iota-carrageenan.

    Directory of Open Access Journals (Sweden)

    Alexandra Hebar

    Full Text Available Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

  3. Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies

    Science.gov (United States)

    Vaccine-associated enhanced respiratory disease (VAERD) can occur in pigs immunized with whole-inactivated influenza virus (WIV) vaccine and subsequently infected with an antigenically divergent virus of the same HA subtype. Live-attenuated influenza virus (LAIV) vaccines administered intranasally h...

  4. Determination of the optimal time of vaccination against infectious bursal disease virus (Gumboro in Algeria

    Directory of Open Access Journals (Sweden)

    Omar Besseboua

    2015-04-01

    Full Text Available This study was conducted to determine the effect of maternally derived antibody (MDA on live vaccine against infectious bursal disease. A total of 140 chicks selected from vaccinated parent stock were used in this investigation. In a preset vaccination schedule, blood samples were collected to check for the actual effect. It was noticed that on day 1 the chicks contained a high level (6400.54 ± 2993.67 of maternally derived antibody that gradually decreased below a positive level within 21 days (365.86 ± 634.46. It was found that a high level of MDA interferes with the vaccine virus, resulting in no immune response. For better immune response, it is suggested that the chickens should be vaccinated at day 21, as the uniformity of MDA is poor (coefficient of the variation [CV] > 30%, and boosted at day 28. Indeed, two vaccinations are necessary to achieve good protection against infectious bursal disease virus of the entire flock.

  5. Reversion to virulence of a subtype B avian metapneumovirus vaccine: is it time for regulators to require availability of vaccine progenitors?

    Science.gov (United States)

    Cecchinato, M; Catelli, E; Lupini, C; Ricchizzi, E; Prosperi, S; Naylor, C J

    2014-08-06

    Empirically derived live avian metapneumovirus (AMPV) vaccines developed during the late 80s and early 90s have generally performed well in controlling turkey rhinotracheitis. Nonetheless, unstable attenuation was previously demonstrated in an AMPV subtype A vaccine. Until now this had not been investigated in subtype B vaccines due to lack of any similar availability of a vaccine progenitor or its sequence. The publication of the full genome sequence for the VCO3 vaccine progenitor facilitated a conclusive investigation of two AMPVs isolated from poults on a farm which had been vaccinated with VCO3 derived vaccine. Full genome sequencing of the isolates and their comparison to sequences of the vaccine and its progenitor, confirmed their vaccine origin. After determining the absence of extraneous infectious agents, one of these virus isolates was inoculated into 1-day-old turkeys in disease secure isolators and shown to cause disease with a severity similar to that caused by virulent field virus. This suggests that instability in live AMPV vaccines may be generalized and highlights the need for availability of vaccine progenitor sequences for the field assessment of all live viral vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. The time-course of protection of the RTS,S vaccine against malaria infections and clinical disease.

    Science.gov (United States)

    Penny, Melissa A; Pemberton-Ross, Peter; Smith, Thomas A

    2015-11-04

    Recent publications have reported follow-up of the RTS,S/AS01 malaria vaccine candidate Phase III trials at 11 African sites for 32 months (or longer). This includes site- and time-specific estimates of incidence and efficacy against clinical disease with four different vaccination schedules. These data allow estimation of the time-course of protection against infection associated with two different ages of vaccination, both with and without a booster dose. Using an ensemble of individual-based stochastic models, each trial cohort in the Phase III trial was simulated assuming many different hypothetical profiles for the vaccine efficacy against infection in time, for both the primary course and boosting dose and including the potential for either exponential or non-exponential decay. The underlying profile of protection was determined by Bayesian fitting of these model predictions to the site- and time-specific incidence of clinical malaria over 32 months (or longer) of follow-up. Using the same stochastic models, projections of clinical efficacy in each of the sites were modelled and compared to available observed trial data. The initial protection of RTS,S immediately following three doses is estimated as providing an efficacy against infection of 65 % (when immunizing infants aged 6-12 weeks old) and 91 % (immunizing children aged 5-17 months old at first vaccination). This protection decays relatively rapidly, with an approximately exponential decay for the 6-12 weeks old cohort (with a half-life of 7.2 months); for the 5-17 months old cohort a biphasic decay with a similar half-life is predicted, with an initial rapid decay followed by a slower decay. The boosting dose was estimated to return protection to an efficacy against infection of 50-55 % for both cohorts. Estimates of clinical efficacy by trial site are consistent with those reported in the trial for all cohorts. The site- and time-specific clinical observations from the RTS,S/AS01 trial data allowed

  7. [Comparison of immune response after oral and intranasal immunization with recombinant Lactobacillus casei expressing ETEC F41].

    Science.gov (United States)

    Liu, Jiankui; Wei, Chunhua; Hou, Xilin; Wang, Guihua; Yu, Liyun

    2009-04-01

    In order to represent a promising strategy for mucosal vaccination, oral or intranasal immunization of Specific Pathogen Free (SPF) BALB/c mice were performed. The mucosal immunity, systemic immune and protective immune responses were compared after immunization with the recombinant Lactobacillus casei (L. casei) harboring enterotoxigenic Escherichia coli (ETEC) F41. The recombinant fusion proteins were detected by Western blot. Surface localization of the fusion protein was verified by immunofluorescence microscopy and flow cytometry. Six-week-old female SPF BALB/c mice (160 heads) were divided into 4 groups for immunization and control. Oral and intranasal immunization of mice was performed with the recombinant strain L. casei harboring pLA-F41 or pLA. For oral immunization, the mice were inoculated daily on days 0 to 4, 7 to 11, 21 to 25, and 49 to 53. A lighter schedule was used for nasal immunization (days 0 to 2, 7 to 9, 21 and 49). Specific anti-F41 IgG antibody in the serum and specific anti-F41 secret immunoglobulin A (sIgA) antibody in the lung, intestines, vagina fluid and feces of mice were detected by indirect ELISA. The mice orally or intranasally immunized with pLA-F41/L. casei and pLA/IL. casei were challenged with standard-type ETEC F41 (C83919) (2 x 10(3) LD50). Mice immunized with pLA-F41/L. casei could produce remarkable anti-F41 antibody level. More than 90% survived in oral immunization group whereas more than 85% survived in intranasal immunization group after challenged with C83919, all dead in the control group. Ninety percent of the pups survived in oral immunization group whereas 80% survived in intranasal immunization group after challenged with C83919, but only a 5% survival rate for pups that were either immunized with a control pLA vector or unimmunized. Oral or intranasal immunization with recombinant L. casei displaying ETEC F41 antigens on the surface induced effective and similar systemic and mucosal immune responses against the

  8. The association between travel time to health facilities and childhood vaccine coverage in rural Ethiopia. A community based cross sectional study.

    Science.gov (United States)

    Okwaraji, Yemisrach B; Mulholland, Kim; Schellenberg, Joanna R M Armstrong; Andarge, Gashaw; Admassu, Mengesha; Edmond, Karen M

    2012-06-22

    Few studies have examined associations between access to health care and childhood vaccine coverage in remote communities that lack motorised transport. This study assessed whether travel time to health facilities was associated with childhood vaccine coverage in a remote area of Ethiopia. This was a cross-sectional study using data from 775 children aged 12-59 months who participated in a household survey between January -July 2010 in Dabat district, north-western Ethiopia. 208 households were randomly selected from each kebele. All children in a household were eligible for inclusion if they were aged between 12-59 months at the time of data collection. Travel time to vaccine providers was collected using a geographical information system (GIS). The primary outcome was the percentage of children in the study population who were vaccinated with the third infant Pentavalent vaccine ([Diphtheria, Tetanus,-Pertussis Hepatitis B, Haemophilus influenza type b] Penta3) in the five years before the survey. We also assessed effects on BCG, Penta1, Penta2 and Measles vaccines. Analysis was conducted using Poisson regression models with robust standard error estimation and the Wald test. Missing vaccination data ranged from 4.6% (36/775) for BCG to 16.4% (127/775) for Penta3 vaccine. In children with complete vaccination records, BCG vaccine had the highest coverage (97.3% [719/739]), Penta3 coverage was (92.9% [602/648]) and Measles vaccine had the lowest coverage (81.7% [564/690]). Children living ≥60mins from a health post were significantly less likely (adjRR = 0.85 [0.79-0.92] p value Travel time also had a highly significant association with BCG (adjRR = 0.95 [0.93-0.98] p value =0.002) and Measles (adjRR = 0.88 [0.79-0.97] p value =0.027) vaccine coverage. Travel time to vaccine providers in health posts appeared to be a barrier to the delivery of infant vaccines in this remote Ethiopian community. New vaccine delivery strategies are needed for the

  9. Time course study of in situ expression of antigens following DNA-vaccination against VHS in rainbow trout (Oncorhynchus mykiss Walbaum) fry

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Lorenzen, Niels; Einer-Jensen, Katja

    2005-01-01

    The present study was performed as a time course study of fish vaccinated with 20 mu g plasmid DNA vaccine encoding either the VHSV G-protein or the VHSV N-protein. Samples of the injection site were collected sequentially over a 7-week period. The study revealed an intense positive staining by i...

  10. Training student pharmacists to administer emergency pediatric influenza vaccine: A comparison of traditional vs. just-in-time training.

    Science.gov (United States)

    Terriff, Colleen M; McKeirnan, Kimberly

    2017-07-01

    This study compared traditional training (TT) and just-in-time training (JITT) of P3 student pharmacists regarding interest, confidence, and comfort pre- and post-training (primary objective); and assessment and administration competency (secondary objective) during a simulated influenza vaccination clinic. Student pharmacists were randomized 1:1 to receive either TT or JITT, completed pre- and post-training surveys assessing interest, confidence and comfort; and evaluated on performance during a simulated emergency infant vaccination. An infant manikin simulated a child <1 year of age, and an actor role-played the mother. All students received a briefing about the simulated mass vaccination prior to their performance assessment. Survey differences between groups were analyzed by ANOVA. The competency assessment was analyzed by a Chi-square or Fisher's exact test for individual steps and Student t-test for mean scores. Pre-training interest was high and maintained post-training. Pre-training confidence and comfort levels were low and improved in both groups. Mean competency scores were comparable between the TT and JITT groups. Comparing groups, TT students more commonly missed proper injection site selection and care; while JITT missed distracting the infant and administration documentation. JITT for student pharmacists to learn skills required to immunize infants elicits similar outcomes (interest, confidence, comfort, and administration competency) as TT for emergency pediatric influenza vaccination. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Linear DNA vaccine prepared by large-scale PCR provides protective immunity against H1N1 influenza virus infection in mice.

    Science.gov (United States)

    Wang, Fei; Chen, Quanjiao; Li, Shuntang; Zhang, Chenyao; Li, Shanshan; Liu, Min; Mei, Kun; Li, Chunhua; Ma, Lixin; Yu, Xiaolan

    2017-06-01

    Linear DNA vaccines provide effective vaccination. However, their application is limited by high cost and small scale of the conventional polymerase chain reaction (PCR) generally used to obtain sufficient amounts of DNA effective against epidemic diseases. In this study, a two-step, large-scale PCR was established using a low-cost DNA polymerase, RKOD, expressed in Pichia pastoris. Two linear DNA vaccines encoding influenza H1N1 hemagglutinin (HA) 1, LEC-HA, and PTO-LEC-HA (with phosphorothioate-modified primers), were produced by the two-step PCR. Protective effects of the vaccines were evaluated in a mouse model. BALB/c mice were immunized three times with the vaccines or a control DNA fragment. All immunized animals were challenged by intranasal administration of a lethal dose of influenza H1N1 virus 2 weeks after the last immunization. Sera of the immunized animals were tested for the presence of HA-specific antibodies, and the total IFN-γ responses induced by linear DNA vaccines were measured. The results showed that the DNA vaccines but not the control DNA induced strong antibody and IFN-γ responses. Additionally, the PTO-LEC-HA vaccine effectively protected the mice against the lethal homologous mouse-adapted virus, with a survival rate of 100% versus 70% in the LEC-HA-vaccinated group, showing that the PTO-LEC-HA vaccine was more effective than LEC-HA. In conclusion, the results indicated that the linear H1N1 HA-coding DNA vaccines induced significant immune responses and protected mice against a lethal virus challenge. Thus, the low-cost, two-step, large-scale PCR can be considered a potential tool for rapid manufacturing of linear DNA vaccines against emerging infectious diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens.

    Science.gov (United States)

    Maassen, Catharina B M; Laman, Jon D; van Holten-Neelen, Conny; Hoogteijling, Linsy; Groenewegen, Lizet; Visser, Lizette; Schellekens, Marc M; Boersma, Wim J A; Claassen, Eric

    2003-12-01

    Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was constructed producing myelin proteins and peptides, including human and guinea pig myelin basic protein (MBP) and proteolipid protein peptide 139-151 (PLP(139-151)). In this study we examined whether these Lactobacillus recombinants are able to induce oral and intranasal tolerance in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received soluble cell extracts of Lactobacillus transformants intranasally three times prior to induction of EAE. For the induction of oral tolerance, rats were fed live transformed lactobacilli for 20 days. Ten days after the first oral administration EAE was induced. Intranasal administration of extracts containing guinea pig MBP (gpMBP) or MBP(72-85) significantly inhibited EAE in Lewis rats. Extracts of control transformants did not reduce EAE. Live lactobacilli expressing guinea pig MBP(72-85) fused to the marker enzyme beta-glucuronidase (beta-gluc) were also able to significantly reduce disease when administered orally. In conclusion, these experiments provide proof of principle that lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and oral) administration. This novel method of mucosal tolerance induction by mucosal administration of recombinant lactobacilli expressing relevant autoantigens could find applications in autoimmune disease in general, such as multiple sclerosis, rheumatoid arthritis and uveitis.

  13. Monitoring of timely and delayed vaccinations: a nation-wide registry-based study of Norwegian children aged < 2 years.

    Science.gov (United States)

    Riise, Øystein Rolandsen; Laake, Ida; Bergsaker, Marianne Adeleide Riise; Nøkleby, Hanne; Haugen, Inger Lise; Storsæter, Jann

    2015-11-13

    Delayed vaccinations increase the risk for vaccine preventable diseases (VPDs). Monitoring of delayed vaccinations by using a national immunisation registry has not been studied in countries recommending a two-dose (3 and 5 months of age) primary series of e.g., pertussis vaccine. Surveillance/monitoring of all vaccinations may improve vaccination programmes functioning. We obtained information from the Norwegian immunisation registry (SYSVAK) on all programme vaccinations received at age up to 730 days in children born in 2010 (n = 63,382). Timely vaccinations were received up to 7 days after the recommended age. Vaccinations were considered delayed if they were received more than one month after the recommended age in the schedule. In vaccinated children, timely administration of the subsequent three doses of pertussis and one dose of measles occurred in 73.8, 47.6, 53.6 and 43.5 % respectively. Delay for one or more programme vaccinations (diphtheria, tetanus, pertussis, polio, Haemophilus influenza type B, invasive pneumococcal disease, measles, mumps or rubella) was present in 28,336 (44.7 %) children. Among those who were delayed the mean duration was 139 days. The proportion of children that had vaccinations delayed differed among counties (range 37.4 %-57.8 %). Immigrant children were more frequently delayed 52.3 % vs. 43.1 %, RR 1.21 (95 % CI 1.19, 1.24). Children scheduled for vaccines in the summer holiday month (July) were more frequently delayed than others (1(st) dose pertussis vaccine 6.5 % vs. 3.9 % RR 1.65 (95 % CI 1.48, 1.85). Priming against pertussis (2(nd) dose), pneumococcal (2(nd) dose) and measles (1(st) dose) was delayed in 16.8, 18.6 and 29.3 % respectively. Vaccinations were frequently delayed. Delayed vaccinations differed among counties and occurred more frequently during the summer vacation (July) and in the immigrant population. Monitoring improves programme surveillance and may be used on an annual basis.

  14. Intranasal immunization with influenza VLPs incorporating membrane-anchored flagellin induces strong heterosubtypic protection.

    Directory of Open Access Journals (Sweden)

    Bao-Zhong Wang

    2010-11-01

    Full Text Available We demonstrated previously that the incorporation of a membrane-anchored form of flagellin into influenza virus-like particles (VLPs improved the immunogenicity of VLPs significantly, inducing partially protective heterosubtypic immunity by intramuscular immunization. Because the efficacy of mucosal vaccination is highly dependent on an adjuvant, and is particularly effective for preventing mucosal infections such as influenza, we determined whether the membrane-anchored flagellin is an efficient adjuvant for VLP vaccines by a mucosal immunization route. We compared the adjuvant effect of membrane-anchored and soluble flagellins for immunization with influenza A/PR8 (H1N1 VLPs by the intranasal route in a mouse model. The results demonstrate that membrane-anchored flagellin is an effective adjuvant for intranasal (IN immunization, inducing enhanced systemic and mucosal antibody responses. High cellular responses were also observed as shown by cytokine production in splenocyte cultures when stimulated with viral antigens. All mice immunized with flagellin-containing VLPs survived challenge with a high lethal dose of homologous virus as well as a high dose heterosubtypic virus challenge (40 LD(50 of A/Philippines/82, H3N2. In contrast, no protection was observed with a standard HA/M1 VLP group upon heterosubtypic challenge. Soluble flagellin exhibited a moderate adjuvant effect when co-administered with VLPs by the mucosal route, as indicated by enhanced systemic and mucosal responses and partial heterosubtypic protection. The membrane-anchored form of flagellin incorporated together with antigen into influenza VLPs is effective as an adjuvant by the mucosal route and unlike standard VLPs, immunization with such chimeric VLPs elicits protective immunity to challenge with a distantly related influenza A virus.

  15. Intranasal oxytocin effects on social cognition: a critique.

    Science.gov (United States)

    Evans, Simon L; Dal Monte, Olga; Noble, Pamela; Averbeck, Bruno B

    2014-09-11

    The last decade has seen a large number of published findings supporting the hypothesis that intranasally delivered oxytocin (OT) can enhance the processing of social stimuli and regulate social emotion-related behaviors such as trust, memory, fidelity, and anxiety. The use of nasal spray for administering OT in behavioral research has become a standard method, but many questions still exist regarding its action. OT is a peptide that cannot cross the blood-brain barrier, and it has yet to be shown that it does indeed reach the brain when delivered intranasally. Given the evidence, it seems highly likely that OT does affect behavior when delivered as a nasal spray. These effects may be driven by at least three possible mechanisms. First, the intranasally delivered OT may diffuse directly into the CNS where it directly engages OT receptors. Second, the intranasally delivered OT may trigger increased central release via an indirect peripheral mechanism. And third, the indirect peripheral effects may directly lead to behavioral effects via some mechanism other than increased central release. Although intranasally delivered OT likely affects behavior, there are conflicting reports as to the exact nature of those behavioral changes: some studies suggest that OT effects are not always "pro-social" and others suggest effects on social behaviors are due to a more general anxiolytic effect. In this critique, we draw from work in healthy human populations and the animal literature to review the mechanistic aspects of intranasal OT delivery, and to discuss intranasal OT effects on social cognition and behavior. We conclude that future work should control carefully for anxiolytic and gender effects, which could underlie inconsistencies in the existing literature. This article is part of a Special Issue entitled Oxytocin and Social Behav. © 2013 Published by Elsevier B.V.

  16. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2015-01-01

    An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

  17. Gender influence in influenza vaccine uptake in Spain: time trends analysis (1995-2006).

    Science.gov (United States)

    Jiménez-García, Rodrigo; Hernández-Barrera, Valentín; de Andres, Ana Lopez; Jimenez-Trujillo, Isabel; Esteban-Hernández, Jesus; Carrasco-Garrido, Pilar

    2010-08-31

    This study aims to analyze gender differences in influenza vaccine coverage and predictors of vaccine uptake in Spain from year 1995 to 2006. We used data obtained from the Spanish National Health Surveys (NHSS) conducted in 1995, 1997, 2001, 2003 and 2006. Only subjects for whom the vaccine was recommended in Spain (age >or=65 years and trends 1995/1997-2006 showed that the coverage has improved for women (OR 1.12 CI 95% 1.09-1.16) and men (OR 1.11 CI 95% 1.06-1.15). Over the whole study period men had 12% greater probability of having received the vaccine. We conclude that in Spain there are significant gender differences in influenza vaccine uptake with lower coverage among women. These differences have remained throughout all years studied. We suggest that possible explanations for the lower uptake among women could include less social support, differences in the health status and provider bias. (c) 2010 Elsevier Ltd. All rights reserved.

  18. The efficacy of intranasal antihistamines in the treatment of allergic rhinitis.

    Science.gov (United States)

    Kaliner, Michael A; Berger, William E; Ratner, Paul H; Siegel, Charles J

    2011-02-01

    To discuss the new use of intranasal antihistamines as first-line therapies, compare and contrast this class of medication with the traditionally available medications, and discuss the potential for intranasal antihistamines to provide relief superior to second-generation oral antihistamines. Review articles and original research articles were retrieved from MEDLINE, OVID, PubMed (1950 to November 2009), personal files of articles, and bibliographies of located articles that addressed the topic of interest. Articles were selected for their relevance to intranasal antihistamines and their role in allergic rhinitis. Publications included reviews, treatment guidelines, and clinical studies (primarily randomized controlled trials) of both children and adults. This panel was charged with reviewing the place of intranasal antihistamines in the spectrum of treatment for allergic rhinitis. Intranasal antihistamines have been shown in numerous randomized, placebo-controlled trials to be more efficacious than the oral antihistamines. Although intranasal corticosteroids are considered by some to be superior to intranasal antihistamines, multiple studies have shown an equal effect of the 2 classes of medication. Both intranasal corticosteroids and intranasal antihistamines have been shown to reduce all symptoms of allergic rhinitis. In addition, some intranasal antihistamines have a more rapid onset of action than intranasal corticosteroids. The future of allergy treatment will likely involve a combination of both intranasal corticosteroids and intranasal antihistamines because of the benefits of local administration and their additive effect on efficacy. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. The association between travel time to health facilities and childhood vaccine coverage in rural Ethiopia. A community based cross sectional study

    Directory of Open Access Journals (Sweden)

    Okwaraji Yemisrach B

    2012-06-01

    Full Text Available Abstract Background Few studies have examined associations between access to health care and childhood vaccine coverage in remote communities that lack motorised transport. This study assessed whether travel time to health facilities was associated with childhood vaccine coverage in a remote area of Ethiopia. Methods This was a cross-sectional study using data from 775 children aged 12–59 months who participated in a household survey between January –July 2010 in Dabat district, north-western Ethiopia. 208 households were randomly selected from each kebele. All children in a household were eligible for inclusion if they were aged between 12–59 months at the time of data collection. Travel time to vaccine providers was collected using a geographical information system (GIS. The primary outcome was the percentage of children in the study population who were vaccinated with the third infant Pentavalent vaccine ([Diphtheria, Tetanus,-Pertussis Hepatitis B, Haemophilus influenza type b] Penta3 in the five years before the survey. We also assessed effects on BCG, Penta1, Penta2 and Measles vaccines. Analysis was conducted using Poisson regression models with robust standard error estimation and the Wald test. Results Missing vaccination data ranged from 4.6% (36/775 for BCG to 16.4% (127/775 for Penta3 vaccine. In children with complete vaccination records, BCG vaccine had the highest coverage (97.3% [719/739], Penta3 coverage was (92.9% [602/648] and Measles vaccine had the lowest coverage (81.7% [564/690]. Children living ≥60mins from a health post were significantly less likely (adjRR = 0.85 [0.79-0.92] p value  Conclusions Travel time to vaccine providers in health posts appeared to be a barrier to the delivery of infant vaccines in this remote Ethiopian community. New vaccine delivery strategies are needed for the hardest to reach children in the African region.

  20. Virus-like particles vaccine containing Clonorchis sinensis tegumental protein induces partial protection against Clonorchis sinensis infection.

    Science.gov (United States)

    Lee, Dong-Hun; Kim, Ah-Ra; Lee, Su-Hwa; Quan, Fu-Shi

    2017-12-29

    Human clonorchiasis, caused by the infection of Clonorchis sinensis, is one of the major health problems in Southeast Asia. However, vaccine efficacy against C. sinensis infection remains largely unknown. In this study, for the first time, we generated virus-like particles (VLPs) vaccine containing the C. sinensis tegumental protein 22.3 kDa (CsTP 22.3) and the influenza matrix protein (M1) as a core protein, and investigated the vaccine efficacy in Sprague-Dawley rats. Intranasal immunization of VLPs vaccine induced C. sinensis-specific IgG, IgG2a and IgG2c in the sera and IgA responses in the feces and intestines. Notably, upon challenge infection with C. sinensis metacercariae, significantly lower adult worm loads (70.2%) were measured in the liver of rats immunized with VLPs, compared to those of naïve rats. Furthermore, VLPs immunization induced antibody secreting cells (ASC) responses and CD4+/CD8+ T cell responses in the spleen. Our results indicated that VLPs vaccine containing C. sinensis CsTP 22.3 kDa provided partial protection against C. sisnensis infection. Thus, VLPs could be a potential vaccine candidate against C. sinensis.

  1. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  2. Mucosal Vaccination and Therapy with Genetically Modified Lactic Acid Bacteria

    NARCIS (Netherlands)

    Wells, J.

    2011-01-01

    Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that

  3. VACCINATION SAFETY: MODERN DATA

    Directory of Open Access Journals (Sweden)

    V.К. Tatochenko

    2007-01-01

    Full Text Available Vaccination aided disease control over infection pathology among the children led to elimination of smallpox and poliomyelitis, drastic decrease of the tuberculous meningitis recurrences, tetanus, measles and other infection diseases and their complications. At the same time, Russia is still afraid to apply certain vaccines. The reasons for that are mainly subjective. This is the unjustified caution related to the fear that it may cause severe vaccine associated complications. The data in view of the lecture indicates the safety of the vaccinal prevention procedures and measures for the prevention of their complications.Key words: vaccinal prevention, vaccination complications, vaccination safety, children.

  4. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  5. Impact of Gender on Pharmocokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Putcha, L.; Lei, Wu.; S-L Chow, Diana

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS), which is commonly experienced by astronauts during space missions. The bioavailability and pharmacokinetics (PK) were evaluated under IND guidelines. Since information is lacking on the effect of gender on the PK of Scopolamine, we examined gender differences in PK parameters of INSCOP at three dose levels of 0.1, 0.2 and 0.4 mg. Methods: Plasma scopolamine concentrations as a function of time data were collected from twelve normal healthy human subjects (6 male/6 female) who participated in a fully randomized double blind crossover study. The PK parameters were derived using WinNonlin. Covariate analysis of PK profiles was performed using NONMEN and statistically compared using a likelihood ratio test on the difference of objective function value (OFV). Statistical significance for covariate analysis was set at Pgender-dependent pharmacokinetics of scopolamine at the high dose level of 0.4 mg. Clearance of the parent compound was significantly faster and the volume of distribution was significantly higher in males than in females, As a result, including gender as a covariate to the pharmacokinetic model of scopolamine offers the best fit for PK modeling of the drug at dose of 0.4 mg or higher.

  6. Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis: a review of randomized, controlled trials.

    Science.gov (United States)

    Nielsen, Lars P; Dahl, Ronald

    2003-01-01

    For several years there has been discussion of whether first-line pharmacological treatment of allergic rhinitis should be antihistamines or intranasal corticosteroids. No well documented, clinically relevant differences seem to exist for individual nonsedating antihistamines in the treatment of allergic rhinitis. Likewise, the current body of literature does not seem to favor any specific intranasal corticosteroid. When comparing efficacy of antihistamines and intranasal corticosteroids in allergic rhinitis, present data favor intranasal corticosteroids. Interestingly, data do not support antihistamines as superior in treating conjunctivitis associated with allergic rhinitis. Safety data from comparative studies in allergic rhinitis do not indicate differences between antihistamines and intranasal corticosteroids. Combining antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis does not provide additional beneficial effects to intranasal corticosteroids alone. Considering present data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis, when compared with antihistamines.

  7. Adult vaccination: Now is the time to realize an unfulfilled potential

    Science.gov (United States)

    Tan, Litjen

    2015-01-01

    Each year, vaccine-preventable diseases kill thousands of adults, both in the United States and across the planet, causing a significant human toll and severe economic burden on the world's healthcare systems. In the United States, while immunization is recognized as one of the most effective primary prevention services that improves health and well-being, adult immunization rates remain low and large gaps exist between national adult immunization goals and actual adult immunization rates. Closing these gaps requires a commitment by national leaders to a multifaceted national strategy to: (1) establish the value of adult vaccines in the eyes of the public, payers, policy makers, and health care professionals; (2) improve access to recommended adult vaccinations by improving the adult vaccine infrastructure in the United States and developing public-private partnerships to facilitate effective immunization behaviors; and (3) ensure fair and appropriate payment for adult immunization. Many of the situations that result in low adult immunizations rates in the United States also exist in many other countries around the world. Successful strategies to improve adult immunization coverage rates will result in reductions in morbidity, mortality, and healthcare costs. All medical and public health stakeholders must now collaborate to realize the significant health benefits that come with a strong adult immunization program. PMID:26091249

  8. Interaction between neonatal vitamin A supplementation and timing of measles vaccination

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Martins, Cesario L; Fisker, Ane B

    2014-01-01

    BACKGROUND: In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.5 months...

  9. Comparison of Oral and Intranasal Midazolam/Ketamine Sedation in 3‒6-year-old Uncooperative Dental Patients

    Directory of Open Access Journals (Sweden)

    Masoud Fallahinejad Ghajari

    2015-07-01

    Full Text Available Background and aims. There are several known sedative drugs, with midazolam and ketamine being the most commonly used drugs in children. The aim of this study was to compare the effect of intranasal and oral midazolam plus ketamine in children with high levels of dental anxiety. Materials and methods. A crossover double-blind clinical trial was conducted on 23 uncooperative children aged 3‒6 (negative or definitely negative by Frankel scale, who required at least two similar dental treatment visits. Cases were ran-domly given ketamine (10 mg/kg and midazolam (0.5 mg/kg through oral or intranasal routes in each visit. The sedative efficacy of the agents was assessed by an overall success rate judged by two independent pediatric dentists based on Houpt’s scale for sedation. Data analysis was carried out using Wilcoxon test and paired t-test. Results. Intranasal administration was more effective in reduction of crying and movement during dental procedures com-pared to oral sedation (P<0.05. Overall behavior control was scored higher in nasal compared to oral routes at the time of LA injection and after 15 minutes (P<0.05. The difference was found to be statistically significant at the start and during treatment. However, the difference was no longer significant after 30 minutes, with the vital signs remaining within physio-logical limits. Recovery time was longer in the intranasal group (P<0.001 with a more sleepy face (P=0.004. Conclusion. Intranasal midazolam/ketamine combination was more satisfactory and effective than the oral route when sedating uncooperative children.

  10. Iatrogenic Cushing’s syndrome caused by intranasal steroid use

    Science.gov (United States)

    Dursun, Fatma; Kirmizibekmez, Heves

    2017-01-01

    Cushing’s syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing’s syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing’s syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency. PMID:28752153

  11. Iatrogenic Cushing's syndrome caused by intranasal steroid use.

    Science.gov (United States)

    Dursun, Fatma; Kirmizibekmez, Heves

    2017-01-01

    Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing's syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing's syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency.

  12. On-time Measles and Pneumococcal Vaccination of Shanghai Children: The Impact of Individual-level and Neighborhood-level Factors.

    Science.gov (United States)

    Wagner, Abram L; Sun, Xiaodong; Huang, Zhuoying; Ren, Jia; Mukherjee, Bhramar; Wells, Eden V; Boulton, Matthew L

    2016-10-01

    Measles-containing vaccines (MCVs) and pneumococcal conjugate vaccines (PCVs) can prevent a large proportion of infant deaths and are recommended by international organizations for inclusion in pediatric immunization schedules. In China, MCV but not PCV is publically funded and access to vaccination may be limited among nonlocals, who are rural migrants to cities. In this study, we estimate the proportion of Shanghai children with on-time MCV and PCV administration, compare vaccination in nonlocals versus locals and assess the impact of township-level characteristics on vaccination outcomes. Data from children in the Shanghai Immunization Program Information System were linked to township-level data from the 2010 China Census. We used generalized estimating equations with logistic regression models to assess the impact of residency and township-level predictors on on-time MCV and PCV administration. Nonlocals had lower vaccination levels than locals. Compared with locals, nonlocals had 0.50 times the odds of MCV dose 1 by 9 months [95% confidence interval (CI): 0.47, 0.53], 0.42 times the odds of MCV dose 2 by 24 months (95% CI: 0.39, 0.45), 0.37 times the odds of PCV by 9 months of age (95% CI: 0.33, 0.42) and 0.41 times the odds of PCV by 24 months of age (95% CI: 0.37, 0.45). Overall, children had less on-time MCV and PCV administration in nonlocal-majority than local-majority townships. Late vaccination negatively impacts disease control efforts in Shanghai. Nonlocals, particularly those living in nonlocal-majority townships, should especially be targeted for vaccination in order to improve disease control efforts in Shanghai.

  13. I-MOVE multicentre case-control study 2010/11 to 2014/15: Is there within-season waning of influenza type/subtype vaccine effectiveness with increasing time since vaccination?

    Science.gov (United States)

    Kissling, Esther; Nunes, Baltazar; Robertson, Chris; Valenciano, Marta; Reuss, Annicka; Larrauri, Amparo; Cohen, Jean Marie; Oroszi, Beatrix; Rizzo, Caterina; Machado, Ausenda; Pitigoi, Daniela; Domegan, Lisa; Paradowska-Stankiewicz, Iwona; Buchholz, Udo; Gherasim, Alin; Daviaud, Isabelle; Horváth, Judit Krisztina; Bella, Antonino; Lupulescu, Emilia; O Donnell, Joan; Korczyńska, Monika; Moren, Alain

    2016-04-21

    Since the 2008/9 influenza season, the I-MOVE multicentre case-control study measures influenza vaccine effectiveness (VE) against medically-attended influenza-like-illness (ILI) laboratory confirmed as influenza. In 2011/12, European studies reported a decline in VE against influenza A(H3N2) within the season. Using combined I-MOVE data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific VE. We modelled influenza type/subtype-specific VE by time since vaccination using a restricted cubic spline, controlling for potential confounders (age, sex, time of onset, chronic conditions). Over 10,000 ILI cases were included in each analysis of influenza A(H3N2), A(H1N1)pdm09 and B; with 4,759, 3,152 and 3,617 influenza positive cases respectively. VE against influenza A(H3N2) reached 50.6% (95% CI: 30.0-65.1) 38 days after vaccination, declined to 0% (95% CI: -18.1-15.2) from 111 days onwards. At day 54 VE against influenza A(H1N1)pdm09 reached 55.3% (95% CI: 37.9-67.9) and remained between this value and 50.3% (95% CI: 34.8-62.1) until season end. VE against influenza B declined from 70.7% (95% CI: 51.3-82.4) 44 days after vaccination to 21.4% (95% CI: -57.4-60.8) at season end. To assess if vaccination campaign strategies need revising more evidence on VE by time since vaccination is urgently needed.

  14. Real-time reverse transcription polymerase chain reaction method for detection of Canine distemper virus modified live vaccine shedding for differentiation from infection with wild-type strains.

    Science.gov (United States)

    Wilkes, Rebecca P; Sanchez, Elena; Riley, Matthew C; Kennedy, Melissa A

    2014-01-01

    Canine distemper virus (CDV) remains a common cause of infectious disease in dogs, particularly in high-density housing situations such as shelters. Vaccination of all dogs against CDV is recommended at the time of admission to animal shelters and many use a modified live virus (MLV) vaccine. From a diagnostic standpoint for dogs with suspected CDV infection, this is problematic because highly sensitive diagnostic real-time reverse transcription polymerase chain reaction (RT-PCR) tests are able to detect MLV virus in clinical samples. Real-time PCR can be used to quantitate amount of virus shedding and can differentiate vaccine strains from wild-type strains when shedding is high. However, differentiation by quantitation is not possible in vaccinated animals during acute infection, when shedding is low and could be mistaken for low level vaccine virus shedding. While there are gel-based RT-PCR assays for differentiation of vaccine strains from field strains based on sequence differences, the sensitivity of these assays is unable to match that of the real-time RT-PCR assay currently used in the authors' laboratory. Therefore, a real-time RT-PCR assay was developed that detects CDV MLV vaccine strains and distinguishes them from wild-type strains based on nucleotide sequence differences, rather than the amount of viral RNA in the sample. The test is highly sensitive, with detection of as few as 5 virus genomic copies (corresponding to 10(-1) TCID(50)). Sequencing of the DNA real-time products also allows phylogenetic differentiation of the wild-type strains. This test will aid diagnosis during outbreaks of CDV in recently vaccinated animals.

  15. Adult vaccination: Now is the time to realize an unfulfilled potential

    OpenAIRE

    Tan, Litjen

    2015-01-01

    Each year, vaccine-preventable diseases kill thousands of adults, both in the United States and across the planet, causing a significant human toll and severe economic burden on the world's healthcare systems. In the United States, while immunization is recognized as one of the most effective primary prevention services that improves health and well-being, adult immunization rates remain low and large gaps exist between national adult immunization goals and actual adult immunization rates. Cl...

  16. Seroprevalence of hepatitis A in Iranian adolescents: is it time to introduce a vaccine?

    Science.gov (United States)

    Hoseini, S G; Kelishadi, R; Ataei, B; Yaran, M; Motlagh, M E; Ardalan, G; Tajadini, M H; Mostafavi, S N

    2016-01-01

    Universal vaccination of children for hepatitis A virus (HAV) has emerged as a cost-effective strategy to prevent this infection in regions with high incidence of symptomatic disease. Age-specific seroprevalence surveys are practical and reliable methods to estimate the rate of susceptibility in populations, and to help the implementation of vaccination policies. We surveyed the age-specific HAV seroprevalence in a nationally representative sample of Iranian adolescent students aged 10-18 years. Serum samples (n = 2494) were tested by enzyme immunoassay for total anti-HAV antibody. The overall rate of HAV seropositivity was 64% [95% confidence interval (CI), 62-66), which increased sharply from 14·8% (95% CI 7-23) at age 10 years to 72·9% (95% CI 68-78) at age 13 years, without a significant increase up to age 18 years. No significant difference in HAV seroprevalence was observed between males and females (63% vs. 65·1%), or urban and rural areas (63·4% vs. 65·2%); the seropositivity rate was similar in four different socioeconomic regions of Iran. We conclude that the seroconversion rate of HAV is high in Iranian adolescents and therefore mass vaccination of children may be necessary and should be considered by national health authorities.

  17. Efficacy of an inactivated virus vaccine for prevention of porcine parvovirus-induced reproductive failure.

    Science.gov (United States)

    Mengeling, W L; Brown, T T; Paul, P S; Gutekunst, D E

    1979-02-01

    Gilts vaccinated IM either once (4 gilts) or twice (2 gilts) with an acetylethyleneimine-inactivated porcine parvovirus (PPV) vaccine before they were bred were subsequently exposed intranasally and orally to virulent PPV at about the 40th day of gestation (from 37 to 43 days). At 2 weeks after vaccination, all had hemagglutination-inhibiting (HI) titers for PPV (from 20 to 80) which decreased by the time the immunity was challenged with virulent virus (from 10 to 40), but increased thereafter (from 160 to 1,280). Titers of singly and doubly vaccinated gilts were similar throughout the experiment. The gilts were killed at about the 84th day of gestation (from 80 to 87 days), and their litters were examined. Litters were comprised of 68 live fetuses and 1 dead fetus (7 to 14 fetuses/litter). Neither viral antigen, PPV, nor homologous HI antibody was found in any of the fetuses. In addition, 4 gilts were kept in contact with the vaccinated gilts and were treated similarly except for vaccination. These 4 gilts remained free of HI antibody until after they were exposed to virulent PPV during gestation. At the time the gilts were killed the titers were 1,280 to 2,560. Their litters were comprised of 11 live fetuses and 26 dead fetuses (8 to 11 fetuses/litter). Virus was isolated from fetuses of all litters. Viral antigen was found in 24 of the dead fetuses and 10 of the live fetuses. All infected live fetuses also had HI antibody for PPV. The 2 boars used to breed vaccinated and nonvaccinated gilts (usually each gilt was bred to each of the 2 boars), but not exposed to virulent PPV, remained free of HI antibody for PPV.

  18. Using real-time polymerase chain reaction as an alternative rapid method for enumeration of colony count in live Brucella vaccines

    Directory of Open Access Journals (Sweden)

    Waleed S. Shell

    2017-06-01

    Full Text Available Aim: Brucellosis is a major bacterial zoonosis of global importance affecting a range of animal species and man worldwide. It has economic, public health, and bio-risk importance. Control and prevention of animal brucellosis mainly depend on accurate diagnostic tools and implementation of effective and safe animal vaccination program. There are three types of animal Brucella live vaccines - Brucella melitensis Rev-1 vaccine, Brucella abortus S19, and B. abortus RB51. Evaluation of these vaccines depends mainly on enumeration of Brucella viable count. At present, used colony count method is time consuming, costly and requires especial skills. Hence, the aim of this study is to use and standardize real-time polymerase chain reaction (RT-PCR as an alternative, quantitative, sensitive, and rapid method to detect the colony count of Brucella in live Brucella vaccine. Materials and Methods: Four batches of different live Brucella vaccines were evaluated using of conventional bacterial count and RT-quantitative PCR (RT-qPCR using BSCP31 gene specific primers and probe. Standard curve was generated from DNA template extracted from 10-fold serial dilution of living B. abortus RB51 vaccine to evaluate the sensitivity of RT-qPCR. Results: Results revealed that three batches of living Brucella vaccines were acceptable for Brucella colony count when traditional bacterial enumeration method was used. Results of RT-qPCR were identical to that of conventional bacterial count. Conclusion: Results concluded that RT-qPCR was relatively sensitive compared to traditional bacterial colony count of these vaccines.

  19. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  20. Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

    Science.gov (United States)

    Hart, Carl L; Gunderson, Erik W; Perez, Audrey; Kirkpatrick, Matthew G; Thurmond, Andrew; Comer, Sandra D; Foltin, Richard W

    2016-01-01

    Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and ‘positive’ subjective effects, with peaks occurring approximately 5–15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. PMID:17851535

  1. Intranasal administration of oxytocin: Behavioral and clinical effects, a review

    NARCIS (Netherlands)

    Veening, J.G.; Olivier, B.

    2013-01-01

    The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. 'Direct-access-pathways'

  2. Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, J C; Madsbad, S; Rasmussen, M H

    1996-01-01

    Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...

  3. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    Science.gov (United States)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  4. Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

    Directory of Open Access Journals (Sweden)

    David Longbottom

    Full Text Available Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus.Three groups of sheep (groups 1, 2 and 3 were experimentally infected with different doses of C. abortus (5×10(3, 5×10(5 and 5×10(7 inclusion forming units (IFU, respectively prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b or were inoculated subcutaneously on day 70 of gestation with 2×10(6 IFU C. abortus (group 5. Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium.The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for controlling infection.

  5. Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

    Science.gov (United States)

    Longbottom, David; Livingstone, Morag; Maley, Stephen; van der Zon, Arjan; Rocchi, Mara; Wilson, Kim; Wheelhouse, Nicholas; Dagleish, Mark; Aitchison, Kevin; Wattegedera, Sean; Nath, Mintu; Entrican, Gary; Buxton, David

    2013-01-01

    Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus. Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×10(3), 5×10(5) and 5×10(7) inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×10(6) IFU C. abortus (group 5). Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium. The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for controlling infection.

  6. [Breastfeeding indicators produced at time of vaccination in four Primary Care Centres in southern Santiago, Chile].

    Science.gov (United States)

    Glisser, Mario Boris; Barragán, Tatiana del Carmen; Weisstaub, Gerardo

    2016-01-01

    To compare official breastfeeding (BF) data with those obtained by interviews conducted during regular vaccination visits. A pilot descriptive study with convenience sampling was conducted by interviewing guardians of children attending vaccination in four Primary Care Centres in south Santiago. BF prevalence indicators were calculated and stratified by age and education of mothers. A comparison was made between the results and the official ones reported by each Centre. Chi-squared (X2) was calculated to evaluate differences (P<.05) RESULTS: A total of 1990 cases were analysed, in which exclusive BF prevalence was 43.4%, 34.2% and 8.8%, at 2, 4, and 6 months, respectively. At the sixth month, official data (41%) was significantly higher (P<.001). Mothers with less than 12 years of schooling have a lower prevalence of exclusive BF at the 4th month than those with higher education (28.4% vs. 37.8%, respectively, P<.05). Even considering the small size of the sample studied, exclusive BF prevalence obtained is surprisingly lower than official reported data. That difference might be explained by: (a) children brought to vaccinations are roughly two fold the number brought to well-child clinics and, (b) potential bias in official data obtained by staff in charge of promotion and education on BF practices, which could distort the results. Further studies are needed to improve the methodology for collecting and analysis BF data. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons.

    Science.gov (United States)

    Salehi, Mohammad Saied; Khazali, Homayoun; Mahmoudi, Fariba; Janahmadi, Mahyar

    2017-08-01

    The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

  8. Vaccine adverse event monitoring systems across the European Union countries: time for unifying efforts.

    LENUS (Irish Health Repository)

    Zanoni, Giovanna

    2009-05-26

    A survey conducted among 26 European Countries within the Vaccine European New Integrated Collaboration Effort (VENICE) project assessed the status of organization in prevention and management of adverse events following immunization (AEFI) and level of interconnection, with the aim at individuating points of strength and weakness. The emerging picture is for a strong political commitment to control AEFIs in Member States (MS), but with consistent heterogeneity in procedures, regulations and capacity of systems to collect, analyze and use data, although with great potentialities. Suggestions are posed by authors to promote actions for unifying strategies and policies among MS.

  9. Protection of dogs for 13 months against Bordetella bronchiseptica and canine parainfluenza virus with a modified live vaccine.

    Science.gov (United States)

    Jacobs, A A C; Theelen, R P H; Jaspers, R; Horspool, L J I; Sutton, D; Bergman, J G H E; Paul, G

    2005-07-02

    Twelve specific pathogen-free (spf) puppies were vaccinated intranasally with a bivalent, modified live vaccine against infectious tracheobronchitis (group 1) and six puppies of the same age and from the same source served as unvaccinated controls (group 2). Both groups were challenged with wild-type Bordetella bronchiseptica and canine parainfluenza virus by the aerosol route 56 weeks after group 1 had been vaccinated, and at the same time six 10-week-old spf puppies from the same source (group 3) were also challenged. Oronasal swabs were taken regularly before and after the challenge, for the isolation of bacteria and viruses, and the dogs were observed for clinical signs for three weeks after the challenge. The control dogs became culture-positive for B bronchiseptica and canine parainfluenza virus, but the isolation yields from the vaccinated group were significantly lower (P<0.05). The mean clinical scores of the vaccinated group were 61 per cent lower than the scores of group 2 (P=0.009), and 90 per cent lower than the scores of group 3 (P=0.001).

  10. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Shufang Fan

    2009-05-01

    Full Text Available The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA and neuraminidase (NA genes of an H5N1 virus A/VN/1203/2004 (clade 1 was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05 (clade 2.3, and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca. AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2. These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.

  11. Particular qualities of intranasal structures conditions in children with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Layko А.

    2016-03-01

    Full Text Available Objective: To examine particular qualities of the intranasal structures state in children and adolescent patients with type 1 diabetes (T1D. Patients and methods. During the period of 2013–2015 161 patients with type 1 were examined having been treated at the endocrinology department of the National Children's Specialized Hospital OKHMATDET and Children's Hospital №6 (Kyiv. The study group included 138 (85.7% patients with type-1 with the changes of intranasal structures, the control group — 23 (14.3% patients with type-1 with no pathology of upper respiratory tract. Among children of the main group — 92 (66.67% boys and 46 (33.33% girls aged 6–17. All children received clinical and laboratory examination in accordance with the protocols, as well as endoscopy of the nasal cavity, nasopharynx, paranasal sinus computed tomography (if necessary. Results. The most pronounced changes of intranasal structures in children with T1D in the study group were identified in the form of the curvature of the nasal septum (IEF. Endoscopic examination of the nasal cavity and nasopharynx in children of the main group diagnosed the hypertrophy of the inferior turbinate in 54% of patients, acute rhinosinusitis — 12%, chronic adenoids, adenoid vegetations in 10%, polyps — 2%. Microcirculatory disorders according to the nail bed capillaroscopy in patients of the main group were observed 3 times more often than the control group. As a result of bulbar microscopy for children with T1D and IEF vascular changes in a single non-niformity of the caliber of vessels were identified in — 75%, unit sakkulyation venules — 50% maendricus tortuosity of the capillaries — 75%, as well as single-venular anastomoses arteriolo — 37.5%. Intra- and extravascular changes in this group of patients have not been identified. Conclusions. The results of studies in children with T1D indicate the need for timely early diagnosis of the state of intranasal structures and

  12. Just-in-time vaccines: Biomineralized calcium phosphate core-immunogen shell nanoparticles induce long-lasting CD8(+) T cell responses in mice.

    Science.gov (United States)

    Zhou, Weibin; Moguche, Albanus O; Chiu, David; Murali-Krishna, Kaja; Baneyx, François

    2014-04-01

    Distributed and on-demand vaccine production could be game-changing for infectious disease treatment in the developing world by providing new therapeutic opportunities and breaking the refrigeration "cold chain". Here, we show that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize a biocompatible adjuvant in a single step. The resulting 50 nm calcium phosphate core-immunogen shell particles are comparable to soluble protein in inducing ovalbumin-specific antibody response and class switch recombination in mice. However, single dose vaccination with nanoparticles leads to higher expansion of ovalbumin-specific CD8(+) T cells upon challenge with an influenza virus bearing the ovalbumin-derived SIINFEKL peptide, and these cells produce high levels of IFN-γ. Furthermore, mice exhibit a robust antigen-specific CD8(+) T cell recall response when challenged with virus 8 months post-immunization. These results underscore the promise of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines. This paper reports that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize into a biocompatible adjuvant in a single step, enabling distributed and on-demand vaccine production and eliminating the need for refrigeration of vaccines. The findings highlight the possibility of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. [The effect of 3 times per year random vaccination of sows against Aujeszky's disease on maternal immunity in a breeding farm].

    Science.gov (United States)

    Vellenga, L; van Beers-Schreurs, H M; Ooms, P; Schorn, H

    1993-11-15

    Research was undertaken to study the effect of a 'three times a year vaccination schedule in sows' against Aujeszky's disease (AD) on the maternal immunity of their offspring at a large pig farm. Only gI-negative sows and piglets were induced in the study. The maternal immunity was measured in the 8-week-old offspring of 6 gilts and 13 sows, vaccinated in early pregnancy and in 8-week-old piglets born from 12 gilts and 21 sows vaccinated 3 weeks prior to farrowing. At an age of 8 weeks only 5 percent of the piglets, born from sows vaccinated during early pregnancy showed antibody titres against AD of > 1:40 in their serum. In piglets born from sows vaccinated 3 weeks prior to farrowing more than 50 (54.4) percent of the piglets showed antibody titres > 1:40 in their serum. It was concluded that using a 'three times a year vaccination schedule' in a gI negative herd may lead to groups of seronegative piglets on breeding and multiplier farms. The implications are discussed.

  14. Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis.

    Science.gov (United States)

    Suzuki, Motohiko; Yokota, Makoto; Nakamura, Yoshihisa; Ozaki, Shinya; Murakami, Shingo

    2017-04-01

    IL-35 was recently identified as an anti-inflammatory cytokine. We previously reported that recombinant fusion protein of murine IL-35 and human IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro. However, it is unclear whether IL-35 can attenuate nasal allergic responses and symptoms of allergic rhinitis in vivo. To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA). Intranasal administration of rIL-35 and intranasal challenge of OVA were then performed. Nasal symptoms were estimated after the last nasal challenge. Nasal tissue and cervical lymph nodes (CLN) were collected. OVA-specific IgE in sera, OVA-specific T cell response, and the production of cytokines (IL-4, IL-5, and IL-10) stimulated by the OVA antigen were measured. The transcription level of Foxp3 and the frequency of CD4 + CD25 + regulatory T cells were also measured. rIL-35 significantly inhibited the number of sneezes and nasal rubbing movements. It also reduced the number of eosinophils in the nasal mucosa and significantly decreased the level of OVA-specific IgE, the OVA-specific T cell proliferation, and the production of IL-4 and IL-5. Furthermore, rIL-35 significantly increased the production of IL-10, the transcription level of Foxp3, and the frequency of CD4 + CD25 + regulatory T cells. This study showed for the first time that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL-35 increases IL-10, Foxp3, and CD4 + CD25 + regulatory T cells in CLN. This study also suggests that intranasal administration of IL-35 can attenuate allergic rhinitis. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  15. Evaluation of a quadrivalent inactivated vaccine for the protection of cattle against diseases due to common viral infections : research report

    Directory of Open Access Journals (Sweden)

    J.R. Patel

    2004-06-01

    Full Text Available Efficacy of an inactivated quadrivalent vaccine containing infectious bovine rhinotracheitis (IBR virus, parainfluenza type 3 (PI3 virus, bovine virus diarrhoea virus (BVDV and bovine respiratory syncytial virus (BRSV was assessed in naive bovine calves to evaluate short-term (4-18 weeks and long-term (24-38 weeks protection following the basic intramuscular vaccination regime of 2 inoculations a month apart. Vaccination was staggered between the long-term and the short-term groups by about 5 months so that both groups, along with a matched group of 6 unvaccinated (control calves, could be challenged at the same time. Sequential challenges at intervals of 3-8 weeks were done in the order: IBR virus (intranasally, IN, PI3 virus (IN and intratracheally, IT, pestiviruses (IN and BRSV (IN and IT. The IBR virus challenge produced febrile rhinotracheitis (FRT in control calves but both the severity and the duration of FRT was significantly reduced in both vaccinated groups. The amount and the duration of IBR virus shed by the vaccinated groups was significantly reduced compared to the control group. Although PI3 virus, pooled pestivirus and BRSV challenges did not result in a noteworthy disease, challenge virus shedding (amount and duration from the upper (all 3 viruses and the lower (BRSV respiratory tracts was significantly reduced in vaccinated groups. After pestivirus challenge, sera and leukocytes from all control calves were infectious for 6-9 days whereas virus was recovered only from leukocytes in vaccinated calves and only for 1.6-2.7 days. Thus a standard course of the quadrivalent vaccine afforded a significant protection against IBR virus, PI3 virus, BVDV and BRSV for at least 6 months.

  16. Influence of maternally-derived antibodies on live attenuated influenza vaccine efficacy in pigs.

    Science.gov (United States)

    Pyo, Hyun Mi; Hlasny, Magda; Zhou, Yan

    2015-07-17

    Vaccination during pregnancy is practiced in swine farms as one measure to control swine influenza virus (SIV) infection in piglets at an early age. Vaccine-induced maternal antibodies transfer to piglets through colostrum and stabilize the herd: however, maternally derived antibodies (MDA) interfere with immune response following influenza vaccination in piglets at the later stage of life. In addition, MDA is related to enhanced respiratory disease in SIV infection. Previously, we have developed a bivalent live attenuated influenza vaccine (LAIV) which harbors both H1 and H3 HAs. We demonstrated vaccination of this LAIV provided protection to homologous and heterologous SIV infection in pigs. In this study we aimed to investigate the influence of MDA on LAIV efficacy. To this end, SIV sero-negative sows were vaccinated with a commercial vaccine. After parturition, nursery piglets were vaccinated with LAIV intranasally or intramuscularly, and were then challenged with SIV. We report that MDA hampered serum antibody response induced by intramuscular vaccination but not by intranasal vaccination of the LAIV. Viral challenge in the presence of MDA caused exacerbated respiratory disease in unvaccinated piglets. In contrast, all LAIV vaccinated piglets were protected from homologous viral infection regardless of the route of vaccination and the presence of MDA. Our results demonstrated that LAIV conferred protection in the presence of MDA without inciting exacerbated respiratory disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Vaccines against poverty

    Science.gov (United States)

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  18. Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels

    Science.gov (United States)

    Perez, Ana Paula; Mundiña-Weilenmann, Cecilia; Romero, Eder Lilia; Morilla, Maria Jose

    2012-01-01

    Background Molecules taken up by olfactory and trigeminal nerve neurons directly access the brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels would increase the residence time of intranasal material, favoring the nose-to-brain delivery. In this first approach, brain radioactivity after intranasal administration of 32P-small interference RNA (siRNA) complexed with poly(amidoamine) G7 dendrimers (siRNA dendriplexes) within in situ-forming mucoadhesive gels, was determined. Materials 32P-siRNA dendriplexes were incorporated into in situ-forming mucoadhesive gels prepared by blending thermosensitive poloxamer (23% w/w) with mucoadhesive chitosan (1% w/w, PxChi) or carbopol (0.25% w/w, PxBCP). Rheological properties, radiolabel release profile, and local toxicity in rat nasal mucosa were determined. The best-suited formulation was intranasally administered to rats, and blood absorption and brain distribution of radioactivity were measured. Results The gelation temperature of both formulations was 23°C. The PxChi liquid showed non-Newtonian pseudoplastic behavior of high consistency and difficult manipulation, and the gel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a Newtonian behavior of low viscosity and easy manipulation, while in the gel phase showed apparent viscosity similar to that of the mucus but higher than that of aqueous solution. The gel released 35% of radiolabel and the released material showed silencing activity in vitro. Three intranasal doses of dendriplexes in PxCBP gel did not damage the rat nasal mucosa. A combination of 32P-siRNA complexation with dendrimers, incorporation of the dendriplexes into PxCBP gel, and administration of two intranasal doses was necessary to achieve higher brain radioactivity than that achieved by intravenous dendriplexes or intranasal naked siRNA. Conclusion The increased radioactivity within the olfactory bulb suggested that the combination above mentioned favored the

  19. Live-Attenuated Respiratory Syncytial Virus Vaccines

    Science.gov (United States)

    Buchholz, Ursula J.; Collins, Peter L.

    2016-01-01

    Live-attenuated respiratory syncytial virus (RSV) vaccines offer several advantages for immunization of infants and young children: (1) they do not cause vaccine-associated enhanced RSV disease; (2) they broadly stimulate innate, humoral, and cellular immunity, both systemically and locally in the respiratory tract; (3) they are delivered intranasally; and (4) they replicate in the upper respiratory tract of young infants despite the presence of passively acquired maternally derived RSV neutralizing antibody. This chapter describes early efforts to develop vaccines through the classic methods of serial cold-passage and chemical mutagenesis, and recent efforts using reverse genetics to derive attenuated derivatives of wild-type (WT) RSV and to develop parainfluenza vaccine vectors that express RSV surface glycoproteins. PMID:24362694

  20. Randomized evaluation of live attenuated vs. inactivated influenza vaccines in schools (RELATIVES) pilot study: a cluster randomized trial.

    Science.gov (United States)

    Kwong, Jeffrey C; Pereira, Jennifer A; Quach, Susan; Pellizzari, Rosana; Dusome, Edwina; Russell, Margaret L; Hamid, Jemila S; Feinberg, Yael; Winter, Anne-Luise; Gubbay, Jonathan B; Sirtonski, Brittany; Moher, Deanna; Sider, Doug; Finkelstein, Michael; Loeb, Mark

    2015-01-15

    School-based influenza immunization can effectively address accessibility barriers, but injected inactivated influenza vaccines (IIV) may not be acceptable to some children and parents in school settings. To better understand the feasibility of offering intranasal live attenuated influenza vaccines (LAIV) through schools, we assessed uptake, stakeholder acceptability, and cost of school-based delivery of LAIV compared to IIV. We piloted an open-label cluster randomized trial involving 10 elementary schools in Peterborough, Ontario during the 2013-2014 influenza vaccination campaign. Schools were randomized to having students receive IIV or LAIV at publicly-funded school-based clinics organized by the local public health department. We measured the percentage of students vaccinated with at least one dose of influenza vaccine at school. Stakeholder acceptability was evaluated through a questionnaire of parents and interviews of public health department personnel and school principals. We compared the costs per dose of vaccine administered, including staff time and costs of vaccines and supplies. Single-dose influenza vaccine uptake was higher for the five schools offering LAIV than for the five offering IIV (19.3% vs. 12.2%, p=0.02). Interviews with nine school principals and five public health department personnel suggested that the clinics ran smoothly with little disruption to school routines, and that LAIV was associated with increased efficiency and calmer children. All interviewees cited unfamiliarity with LAIV and the study recruitment package length as potential reasons for low uptake. The cost per vaccine dose administered was $38.67 for IIV and $43.50 for LAIV. Use of LAIV in school-based clinics was associated with increased vaccine uptake and the perception among immunizing staff of reduced child anxiety, but also slightly higher vaccine administration costs, compared to IIV. However, uptake was low for both groups. More effective strategies to promote

  1. Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy.

    Science.gov (United States)

    Van Woensel, Matthias; Mathivet, Thomas; Wauthoz, Nathalie; Rosière, Rémi; Garg, Abhishek D; Agostinis, Patrizia; Mathieu, Véronique; Kiss, Robert; Lefranc, Florence; Boon, Louis; Belmans, Jochen; Van Gool, Stefaan W; Gerhardt, Holger; Amighi, Karim; De Vleeschouwer, Steven

    2017-04-27

    In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages' polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy.

  2. Targeting glioblastoma via intranasal administration of Ff bacteriophages.

    Science.gov (United States)

    Dor-On, Eyal; Solomon, Beka

    2015-01-01

    Bacteriophages (phages) are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies.

  3. The comparative value of various employer-sponsored influenza vaccination clinics.

    Science.gov (United States)

    Zimmerman, Richard K; Wiringa, Ann E; Nowalk, Mary Patricia; Lin, Chyongchiou J; Rousculp, Matthew D; Mitgang, Elizabeth A; Lee, Bruce Y

    2012-09-01

    Many US firms offer influenza vaccination clinics to prevent lost productivity due to influenza. Strategies to promote and offer vaccination differ, and the economic value of the strategies is unknown. Decision analytic modeling and Monte Carlo probabilistic sensitivity analyses estimated the one-season cost-consequences of three types of influenza clinics (trivalent inactivated influenza vaccine only, vaccine choice [trivalent inactivated influenza or intranasal {live attenuated influenza} vaccine], or vaccine choice plus incentive) in firms of 50 and 250 employees, from the employer's perspective. On-site influenza vaccination was generally cost-saving over no vaccination. For the scenario of vaccine effectiveness of 70% and intermediate transmissibility, the incremental costs per employee for a firm of 50 employees were -$6.41 (ie, cost savings) for inactivated vaccine only versus no vaccination, -$1.48 for vaccine choice versus inactivated vaccine, and $1.84 for vaccine choice plus incentive versus vaccine choice. Clinics offering a choice of vaccines were slightly less costly under many scenarios. Generally, incremental costs were lower (1) in larger firms; (2) when influenza was assumed to be more contagious; and (3) when vaccine effectiveness was assumed to be higher. Employer-sponsored influenza vaccination clinics are generally cost-saving.

  4. Low cytotoxicity effect of dendrosome as an efficient carrier for rotavirus VP2 gene transferring into a human lung cell line : dendrosome, as a novel intranasally gene porter.

    Science.gov (United States)

    Pourasgari, Farzaneh; Ahmadian, Shahin; Salmanian, Ali Hatef; Sarbolouki, Mohammad Nabi; Massumi, Mohammad

    2009-01-01

    The efficiency of dendrosome (a gene porter) was assessed in transferring recombinant human rotavirus VP2 cDNA into A549, a human lung cell line. After gene transferring, transmission electron microscopy showed core-like particles (CLPs) formation in the transfected cells both with dendrosome and lipofectamine porters. In addition, western blotting analysis showed that the expression of VP2 gene was almost equal in the dendrosome and lipofectamine-transfected cells. Also, the cytotoxicity studies revealed that dendrosome had a lower cytotoxicity than lipofectamine. Therefore, our study may introduce dendrosome as a possible carrier for gene transferring into the human lung cell line, especially, for intranasally administration of DNA vaccines.

  5. BVDV vaccination in North America: risks versus benefits.

    Science.gov (United States)

    Griebel, Philip J

    2015-06-01

    The control and prevention of bovine viral diarrhea virus (BVDV) infections has provided substantial challenges. Viral genetic variation, persistent infections, and viral tropism for immune cells have complicated disease control strategies. Vaccination has, however, provided an effective tool to prevent acute systemic infections and increase reproductive efficiency through fetal protection. There has been substantial controversy about the safety and efficacy of BVDV vaccines, especially when comparing killed versus modified-live viral (MLV) vaccines. Furthermore, numerous vaccination protocols have been proposed to protect the fetus and ensure maternal antibody transfer to the calf. These issues have been further complicated by reports of immune suppression during natural infections and following vaccination. While killed BVDV vaccines provide the greatest safety, their limited immunogenicity makes multiple vaccinations necessary. In contrast, MLV BVDV vaccines induce a broader range of immune responses with a longer duration of immunity, but require strategic vaccination to minimize potential risks. Vaccination strategies for breeding females and young calves, in the face of maternal antibody, are discussed. With intranasal vaccination of young calves it is possible to avoid maternal antibody interference and induce immune memory that persists for 6-8 months. Thus, with an integrated vaccination protocol for both breeding cows and calves it is possible to maximize disease protection while minimizing vaccine risks.

  6. Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

    Science.gov (United States)

    2017-10-01

    people with MS. The study will also evaluate the impact of intranasal insulin on measures of oxidative stress , axonal injury, cellular stress ...impaired cognitive function, which is common and present in over 60% of individuals with MS. Attention, memory , executive functioning, and especially... memory . Insulin is present at high levels in the brain and when these levels are decreased, there may be learning and memory impairments. Moreover

  7. Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

    Science.gov (United States)

    Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

    2012-01-01

    Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

  8. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  9. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2015-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed....... This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30...... March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic...

  10. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, H.K.; Gøtzsche, Peter C.; Johansen, Helle Krogh

    2008-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. OBJECTIVES......: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search May 2008) and PubMed using the terms vaccin* AND cystic...... fibrosis (last search May 2008). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently selected trials...

  11. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    Science.gov (United States)

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2008-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days. PMID:18078723

  12. Vaccine-associated hypersensitivity.

    Science.gov (United States)

    McNeil, Michael M; DeStefano, Frank

    2018-02-01

    Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell-mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines' antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being. Published by Elsevier Inc.

  13. Antidepressant effect of recombinant NT4-NAP/AAV on social isolated mice through intranasal route.

    Science.gov (United States)

    Liu, Fei; Liu, You-Ping; Lei, Gang; Liu, Peng; Chu, Zheng; Gao, Cheng-Ge; Dang, Yong-Hui

    2017-02-07

    The purpose of the present study was to observe the depression-like behavior induced by social isolation; detect the antidepressant effect of a recombinant adeno-associated virus (AAV) expressing NAP on social isolation mice by intranasal delivery. After construction of NT4-NAP/AAV, expression of NAP was confirmed in vitro. 3-week-old C57/BL mice were bred individually in cages as social isolation-rearing. Six weeks later, the first subset of mice underwent behavioral tests and western blot; the second was for enzyme-linked immunosorbent assay. NT4-NAP/AAV was delivered quaque die by nasal administration for consecutive 10 days before behavioral test. Several depression-like behaviors were observed in social isolation mice, including decreased relative sucrose preference, longer immobility time in forced swimming test, lower plasma corticosterone and decreased brain-derived neurotrophic factor in hippocampus. Thus, social isolation procedure appears to be an animal model of depression with good face and construct validity. What's more, the antidepressant effect in social isolation-rearing mice was observed after intranasal administration of NT4-NAP/AAV, suggesting that this might be a promising therapeutic strategy for depressive disorder.

  14. Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

    Science.gov (United States)

    Ma, Xian-Cang; Chu, Zheng; Zhang, Xiao-Ling; Jiang, Wen-Hui; Jia, Min; Dang, Yong-Hui; Gao, Cheng-Ge

    2016-06-01

    The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

  15. Formulation and optimization of mucoadhesive microemulsion containing mirtazapine for intranasal delivery

    Directory of Open Access Journals (Sweden)

    Hetal P Thakkar

    2014-01-01

    Full Text Available Background: Mirtazapine, an antidepressant drug, has absolute bioavailability of only 50% due to high first pass metabolism. Aim: The purpose of this study was to develop and optimize mucoadhesive microemulsion containing mirtazapine for intranasal delivery. Materials and Methods: Based on solubility study, Capmul Medium chain Monoglyceride, Tween 80 and polyethylene glycol (PEG 400 were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 3:1% w/w ratio (Tween 80: PEG 400 was selected for formulation development. The prepared microemulsions were optimized for globule size, zeta potential, % transmittance and polydispersity index. The optimized batch was further characterized for % drug content, conductivity and transmission electron microscopy. Results and Conclusion: All the parameters showed the suitability of microemulsion of mirtazapine for intranasal delivery. Chitosan (0.5% w/w was used as a polymer for the preparation of mucoadhesive microemulsion to enhance the retention time in the nasal mucosa. Results of nasal toxicity study using excised sheep nasal mucosa showed comparatively no damage to epithelium and so formulation was considered safe for nasal administration. mirtazapine mucoadhesive microemulsion showed the highest percentage of diffusion (57.11 ± 0.710% after 210 min during in-vitro drug diffusion study through sheep nasal mucosa, followed by mirtazapine microemulsion (46.08 ± 0.674% and finally by mirtazapine solution (17.63 ± 0.612%.

  16. A ‘post-honeymoon’ measles epidemic in Burundi: mathematical model-based analysis and implications for vaccination timing

    Directory of Open Access Journals (Sweden)

    Katelyn C. Corey

    2016-09-01

    Full Text Available Using a mathematical model with realistic demography, we analyze a large outbreak of measles in Muyinga sector in rural Burundi in 1988–1989. We generate simulated epidemic curves and age × time epidemic surfaces, which we qualitatively and quantitatively compare with the data. Our findings suggest that supplementary immunization activities (SIAs should be used in places where routine vaccination cannot keep up with the increasing numbers of susceptible individuals resulting from population growth or from logistical problems such as cold chain maintenance. We use the model to characterize the relationship between SIA frequency and SIA age range necessary to suppress measles outbreaks. If SIAs are less frequent, they must expand their target age range.

  17. Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

    Science.gov (United States)

    Brünner, Yvonne F; Rodriguez-Raecke, Rea; Mutic, Smiljana; Benedict, Christian; Freiherr, Jessica

    2016-10-01

    This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

    Science.gov (United States)

    Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

    2015-09-01

    To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Optimal timing of influenza vaccination in patients with human immunodeficiency virus: a Markov cohort model based on serial study participant hemoagglutination inhibition titers.

    Science.gov (United States)

    Werker, Gregory R; Sharif, Behnam; Sun, Huiying; Cooper, Curtis; Bansback, Nick; Anis, Aslam H

    2014-02-03

    Seasonal influenza vaccination offers one of the best population-level protections against influenza-like illness (ILI). For most people, a single dose prior to the flu season offers adequate immunogenicity. HIV+ patients, however, tend to exhibit a shorter period of clinical protection, and therefore may not retain immunogenicity for the entire season. Building on the work of Nosyk et al. (2011) that determined a single dose is the optimal dosing strategy for HIV+ patients, we investigate the optimal time to administer this vaccination. Using data from the "single dose" treatment arm of an RCT conducted at 12 CIHR Canadian HIV Trials Network sites we estimated semimonthly clinical seroprotection levels for a cohort (N=93) based on HAI titer levels. These estimates were combined with CDC attack rate data for the three main strains of seasonal influenza to estimate instances of ILI over different vaccination timing strategies. Using bootstrap resampling of the cohort, nine years of CDC data, and parameter distributions, we developed a Markov cohort model that included probabilistic sensitivity analysis. Cost, quality adjusted life-years (QALYs), and net monetary benefits are presented for each timing strategy. The beginning of December is the optimal time for HIV+ patients to receive the seasonal influenza vaccine. Assuming a willingness-to-pay threshold of $50,000, the net monetary benefit associated with a Dec 1 vaccination date is $19,501.49 and the annual QALY was 0.833744. Our results support a policy of administering the seasonal influenza vaccination for this population in the middle of November or beginning of December, assuming nothing is know about the upcoming flu season. But because the difference in between this strategy and the CDC guideline is small-12 deaths averted per year and a savings of $60 million across the HIV+ population in the US-more research is needed concerning strategies for subpopulations. Copyright © 2013 Elsevier Ltd. All rights

  20. [Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles].

    Science.gov (United States)

    Lu, Jin; Guo, Li-Wei; Fu, Ting-Ming; Zhu, Guo-Long; Dai, Zhen-Nan; Zhan, Guan-Jun; Chen, Li-Li

    2017-06-01

    PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration. Copyright© by the Chinese Pharmaceutical Association.

  1. Dual-emission fluorescence resonance energy transfer (FRET) real-time PCR differentiates feline immunodeficiency virus subtypes and discriminates infected from vaccinated cats.

    Science.gov (United States)

    Wang, Chengming; Johnson, Calvin M; Ahluwalia, Sudhir K; Chowdhury, Erfan; Li, Yihang; Gao, Dongya; Poudel, Anil; Rahman, K Shamsur; Kaltenboeck, Bernhard

    2010-05-01

    Feline immunodeficiency virus (FIV) is among the most common infectious agents of cats. Five well-characterized FIV subtypes, A, B, C, D, and E, are recognized worldwide. As in HIV diagnosis, serum antibodies against FIV classically serve as an indicator of infection status. After the introduction of an inactivated FIV vaccine, this approach has become problematic, since antibodies generated by vaccination are indistinguishable from antibodies in response to infection. However, PCR detection of host-cell-integrated FIV DNA will differentiate infection-derived antibody from vaccination-derived positivity because presumably the RNA of inactivated vaccine virus will not integrate into the host genome. In this study, we established a gag gene-based dual-emission fluorescence resonance energy transfer (FRET) real-time PCR that amplifies single-target copies of all known FIV strains and differentiates five FIV subtypes. All blood samples from experimentally FIV-infected cats (n=5) were antibody positive and highly positive in the FIV PCR. In contrast, nine cats became antibody positive after FIV vaccination but remained negative in the FIV PCR. Of 101 FIV antibody-positive feline blood specimens submitted for FIV PCR diagnosis, 61 were positive (60%). A total of 23 of the positive PCRs identified subtype A, 11 identified subtype B1, 11 identified subtype B2/E, and 16 identified subtype C. FIV subtype D was not detected in any submitted specimens even though 13 blood specimens were from cats known to have received the FIV vaccine, which contains FIV subtype A and D inactivated virions. Therefore, this PCR quantitatively identifies FIV subtypes and unambiguously discriminates between FIV-vaccinated and FIV-infected cats.

  2. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    Science.gov (United States)

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  3. Transient facial nerve paralysis (Bell's palsy following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin.

    Directory of Open Access Journals (Sweden)

    David J M Lewis

    2009-09-01

    Full Text Available An association was previously established between facial nerve paralysis (Bell's palsy and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT adjuvant. The individual component(s responsible for paralysis were not identified, and the vaccine was withdrawn.Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63, underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63.While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes.

  4. Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin

    Science.gov (United States)

    Lewis, David J. M.; Huo, Zhiming; Barnett, Susan; Kromann, Ingrid; Giemza, Rafaela; Galiza, Eva; Woodrow, Maria; Thierry-Carstensen, Birgit; Andersen, Peter; Novicki, Deborah; Del Giudice, Giuseppe; Rappuoli, Rino

    2009-01-01

    Background An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. Methodology/Principal Findings Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. Conclusions/Significance While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT–derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes. PMID:19756141

  5. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

    2016-08-01

    Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

  6. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

    Directory of Open Access Journals (Sweden)

    Sanne Terryn

    2016-08-01

    Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

  7. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

    2016-01-01

    Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

  8. Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

    Science.gov (United States)

    In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...

  9. Coverage and timing of children's vaccination: an evaluation of the expanded programme on immunisation in The Gambia.

    Directory of Open Access Journals (Sweden)

    Susana Scott

    Full Text Available To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI in The Gambia.Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health and Demographic Surveillance System (FHDSS, the Basse Health and Demographic Surveillance System (BHDSS, the Kiang West Demographic surveillance system (KWDSS, a cluster survey in the more urban Western Health Region (WR and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination.BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination.The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage.

  10. Technical Transformation of Biodefense Vaccines

    Science.gov (United States)

    Lu, Shan; Wang, Shixia

    2013-01-01

    Biodefense vaccines are developed against a diverse group of pathogens. Vaccines were developed for some of these pathogens a long time ago but they are facing new challenges to move beyond the old manufacturing technologies. New vaccines to be developed against other pathogens have to determine whether to follow traditional vaccination strategies or to seek new approaches. Advances in basic immunology and recombinant DNA technology have fundamentally transformed the process of formulating a vaccine concept, optimizing protective antigens, and selecting the most effective vaccine delivery approach for candidate biodefense vaccines. PMID:19837293

  11. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... component) of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by ...

  12. Intranasal delivery of cholera toxin induces th17-dominated T-cell response to bystander antigens.

    Directory of Open Access Journals (Sweden)

    Jee-Boong Lee

    Full Text Available Cholera toxin (CT is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that CT promotes T helper type 2 (Th2 response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of CT adjuvanticity to demarcate T helper responses.

  13. Improving influenza vaccination rates in the workplace: a randomized trial.

    Science.gov (United States)

    Nowalk, Mary Patricia; Lin, Chyongchiou J; Toback, Seth L; Rousculp, Matthew D; Eby, Charles; Raymund, Mahlon; Zimmerman, Richard K

    2010-03-01

    To minimize absenteeism resulting from influenza, employers frequently offer on-site influenza vaccination to employees. Yet the level of uptake of vaccine is low among working adults. This study was designed to increase workplace influenza vaccination rates by offering both a choice of intranasal (LAIV) and injectable (TIV) influenza vaccines to eligible employees, and an incentive for being vaccinated, and by increasing awareness of the vaccine clinic. This study used a stratified randomized cluster trial. A total of 12,222 employees in 53 U.S. companies with previous influenza vaccine clinics were examined. Control sites advertised and offered vaccine clinics as previously done. Choice sites offered LAIV or TIV and maintained their previous advertising level but promoted the choice of vaccines. Choice Plus sites increased advertising and promoted and offered a choice of vaccines and a nominal incentive. These included vaccination rates among eligible employees. Hierarchic linear modeling (HLM) was used to determine factors associated with vaccination. The overall vaccination rate increased from 39% in 2007-2008 to 46% in 2008-2009 (pvaccination rates for LAIV was 6.5% for Choice versus Control and 9.9% for Choice Plus versus Control (both p or =50 years (p=0.024). Rates of TIV did not change in workers aged 18-49 years in either intervention arm or in workers aged > or =50 years in the Choice arm. In HLM analyses, factors significantly associated with increased vaccination were older age, female gender, previous company vaccination rate, and the Choice Plus intervention. An incentive for vaccination, an intensified advertising campaign, and offering a choice of influenza vaccines improved vaccination rates in the workplace. Copyright (c) 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  14. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

    Science.gov (United States)

    McNeil, Michael M; Gee, Julianne; Weintraub, Eric S; Belongia, Edward A; Lee, Grace M; Glanz, Jason M; Nordin, James D; Klein, Nicola P; Baxter, Roger; Naleway, Allison L; Jackson, Lisa A; Omer, Saad B; Jacobsen, Steven J; DeStefano, Frank

    2014-09-22

    The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods. Published by Elsevier Ltd.

  15. Evaluation of response to bovine viral diarrhea virus type 2 vaccination and timing of weaning on yearling ultrasound body composition, performance, and carcass quality traits in Angus calves

    Science.gov (United States)

    There are concerns about antagonisms between immunity and animal productivity in livestock production. The objective of this study was to evaluate the effect of antibody levels through a response to vaccination protocol, weaning timing, and their interaction on performance and carcass quality traits...

  16. Quantitative real-time PCR study on persistence of pDNA vaccine pVax-Hsp60 TM814 in beef muscles

    Czech Academy of Sciences Publication Activity Database

    Orság, P.; Kvardová, V.; Raška, M.; Miller, A. D.; Ledvina, Miroslav; Turánek, J.

    2008-01-01

    Roč. 6, č. 11 (2008), s. 1-11 ISSN 1479-0556 R&D Projects: GA MZe QF3115 Institutional research plan: CEZ:AV0Z40550506 Keywords : DNA vaccine * real-time PCR * liposomes Subject RIV: CC - Organic Chemistry

  17. Studies on Lyophilization of Sabin Vaccine. 2. Investigation on Long Time Incubation at High and Low Temperatures of Lyophilized Sabin Vaccine

    OpenAIRE

    塩見, 洋; 浦沢, 价子; 浦沢, 正三

    1998-01-01

    Lyophilization of vaccine is one of the possible options for the development of a heat-stable poliovaccine. In our previous study in which conditions affecting the lyophilization of Sabin poliovaccine were investigated, it was found that infectivity titration of lyophilized viruses was under at least three kind of variabilities i. e., i) the variability among different lyophilization experi-ments, ii) the variability within the same lyophilization experiment and iii) the variability inherent ...

  18. Vaccine hesitancy

    Science.gov (United States)

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  19. Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

    Science.gov (United States)

    Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

    2017-08-12

    Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valuechildhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers

  20. Vaccines as Epidemic Insurance

    Directory of Open Access Journals (Sweden)

    Mark V. Pauly

    2017-10-01

    Full Text Available This paper explores the relationship between the research for and development of vaccines against global pandemics and insurance. It shows that development in advance of pandemics of a portfolio of effective and government-approved vaccines does have some insurance properties: it requires incurring costs that are certain (the costs of discovering, developing, and testing vaccines in return for protection against large losses (if a pandemic treatable with one of the vaccines occurs but also with the possibility of no benefit (from a vaccine against a disease that never reaches the pandemic stage. It then argues that insurance against the latter event might usefully be offered to organizations developing vaccines, and explores the benefits of insurance payments to or on behalf of countries who suffer from unpredictable pandemics. These ideas are then related to recent government, industry, and philanthropic efforts to develop better policies to make vaccines against pandemics available on a timely basis.

  1. Pertussis vaccination in pregnancy.

    Science.gov (United States)

    Healy, C Mary

    2016-08-02

    Pertussis has had a resurgence with the highest incidence and complication rates in young infants, and deaths occurring mainly at Pertussis vaccination in pregnancy may protect infants through passive and active transfer of maternal antibodies that protect the infant until the primary immunization series. Studies show vaccinating pregnant women with acellular pertussis vaccine is safe for mother and infant, immunogenic with efficient transfer of antibodies to infants, and effective in preventing pertussis in young infants. Vaccine uptake in pregnant women is sub-optimal, but provider recommendation is the most important factor in improving vaccination rates. Studies are ongoing to determine the best timing of vaccination to protect infants, and into other strategies. Vaccinating pregnant women offers hope to prevent pertussis-related morbidity and mortality in infants worldwide.

  2. Varicella complications: Is it time to consider a routine varicella vaccination?

    Directory of Open Access Journals (Sweden)

    Dulović Olga

    2010-01-01

    common complication: 173/279 (62%, followed by skin infections (2.9%, bacterial respiratory infections (2,2%, and more than one complication (2.3%. Pneumonia was more common in adults than in children (7 : 1. In children skin infections were the most common complications (16.4%, followed by cerebelitis (13.3%, viral pneumonia (12.8%, bacterial respiratory infections (7.7%, encephalitis (3.6%, and more than one complication (4.1%. Neuroinfections were more common in children than in adults (6:1, as well as bacterial skin infections (4 : 1. Two patients died (0,4%. Conclusion. There was no difference in the incidence of varicella complication in children and adults, but the type of complication differed. In children the most common complications were skin and neurological infections, while in adults it was varicella pneumonia. These data provide a baseline for estimating the burden of varicella in Belgrade and support the inclusion of varicella vaccine in childhood immunisation program in Serbia.

  3. [Varicella complications: is it time to consider a routine varicella vaccination?].

    Science.gov (United States)

    Dulović, Olga; Gvozdenović, Eleonora; Nikolić, Jelena; Spurnić, Aleksandra Radovanović; Katanić, Natasa; Kovarević-Pavićević, Dragana

    2010-07-01

    than one complication (2.3%). Pneumonia was more common in adults than in children (7:1). In children skin infections were the most common complications (16.4%), followed by cerebelitis (13.3%), viral pneumonia (12.8%), bacterial respiratory infections (7.7%), encephalitis (3.6%), and more than one complication (4.1%). Neuroinfections were more common in children than in adults (6:1), as well as bacterial skin infections (4:1). Two patients died (0.4%). There was no difference in the incidence of varicella complication in children and adults, but the type of complication differed. In children the most common complications were skin and neurological infections, while in adults it was varicella pneumonia. These data provide a baseline for estimating the burden of varicella in Belgrade and support the inclusion of varicella vaccine in childhood immunisation program in Serbia.

  4. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    International Nuclear Information System (INIS)

    Jain, Darshana S.; Bajaj, Amrita N.; Athawale, Rajani B.; Shikhande, Shruti S.; Pandey, Abhijeet; Goel, Peeyush N.; Gude, Rajiv P.; Patil, Satish; Raut, Preeti

    2016-01-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  5. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Darshana S., E-mail: darshanaj_cup@yahoo.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Bajaj, Amrita N. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Athawale, Rajani B., E-mail: rajani.athawale@gmail.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Shikhande, Shruti S. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Pandey, Abhijeet [H. R Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra (India); Goel, Peeyush N.; Gude, Rajiv P. [Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 210 (India); Patil, Satish; Raut, Preeti [Cipla Pvt. Ltd., Vikhroli (West), Mumbai (India)

    2016-06-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  6. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates.

    Science.gov (United States)

    Todd, Thomas E; Tibi, Omar; Lin, Yu; Sayers, Samantha; Bronner, Denise N; Xiang, Zuoshuang; He, Yongqun

    2013-01-01

    ) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination. Literature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases.

  7. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

    Science.gov (United States)

    2013-01-01

    challenge pathogen strain) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination. Conclusions Literature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases. PMID:23735014

  8. In vivo Biodistribution of a Highly Attenuated Recombinant Vesicular Stomatitis Virus Expressing HIV-1 Gag Following Intramuscular, Intranasal, or Intravenous Inoculation

    Science.gov (United States)

    Johnson, J. Erik; Coleman, John W.; Kalyan, Narender K.; Calderon, Priscilla; Wright, Kevin J.; Obregon, Jennifer; Ogin-Wilson, Eleanor; Natuk, Robert J.; Clarke, David K.; Udem, Stephen A.; Cooper, David; Hendry, R. Michael

    2009-01-01

    Recombinant vesicular stomatitis viruses (rVSVs) are being developed as potential HIV-1 vaccine candidates. To characterize the in vivo replication and dissemination of rVSV vectors in mice, high doses of a highly attenuated vector expressing HIV-1 Gag, rVSVIN- N4CT9-Gag1, and a prototypic reference virus, rVSVIN-HIVGag5, were delivered intramuscularly (IM), intranasally (IN), or intravenously (IV). We used quantitative, real-time RT-PCR (Q-PCR) and standard plaque assays to measure the temporal dissemination of these viruses to various tissues. Following IM inoculation, both viruses were detected primarily at the injection site as well as in draining lymph nodes; neither virus induced significant weight loss, pathologic signs, or evidence of neuroinvasion. In contrast, following IN inoculation, the prototypic virus was detected in all tissues tested and caused significant weight loss leading to death. IN administration of rVSVIN- N4CT9-Gag1 resulted in detection in numerous tissues (brain, lung, nasal turbinates, and lymph nodes) albeit in significantly reduced levels, which caused little or no weight loss nor any mortality. Following IV inoculation, both prototypic and attenuated viruses were detected by Q-PCR in all tissues tested. In contrast to the prototype, rVSVIN-N4CT9-Gag1 viral loads were significantly lower in all organs tested, and no infectious virus was detected in the brain following IV inoculation, despite the presence of viral RNA. These studies demonstrated significant differences in the biodistribution patterns of and the associated pathogenicity engendered by the prototypic and attenuated vectors in a highly susceptible host. PMID:19428903

  9. Roles of adjuvant and route of vaccination in antibody response and protection engendered by a synthetic matrix protein 2-based influenza A virus vaccine in the mouse

    Directory of Open Access Journals (Sweden)

    Cudic Mare

    2007-10-01

    Full Text Available Abstract Background The M2 ectodomain (M2e of influenza A virus (IAV strains that have circulated in humans during the past 90 years shows remarkably little structural diversity. Since M2e-specific antibodies (Abs are capable of restricting IAV replication in vivo but are present only at minimal concentration in human sera, efforts are being made to develop a M2e-specific vaccine. We are exploring a synthetic multiple antigenic peptide (MAP vaccine and here report on the role of adjuvants (cholera toxin and immunostimulatory oligodeoxynucleotide and route of immunization on Ab response and strength of protection. Results Independent of adjuvants and immunization route, on average 87% of the M2e-MAP-induced Abs were specific for M2e peptide and a variable fraction of these M2e(pep-specific Abs (average 15% cross-reacted with presumably native M2e expressed by M2-transfected cells. The titer of these cross-reactive M2e(pep-nat-specific Abs in sera of parenterally immunized mice displayed a sigmoidal relation to level of protection, with EC50 of ~20 μg Ab/ml serum, though experiments with passive M2e(pep-nat Abs indicated that serum Abs did not fully account for protection in parenterally vaccinated mice, particularly in upper airways. Intranasal vaccination engendered stronger protection and a higher proportion of G2a Abs than parenteral vaccination, and the strength of protection failed to correlate with M2e(pep-nat-specific serum Ab titers, suggesting a role of airway-associated immunity in protection of intranasally vaccinated mice. Intranasal administration of M2e-MAP without adjuvant engendered no response but coadministration with infectious IAV slightly enhanced the M2e(pep-nat Ab response and protection compared to vaccination with IAV or adjuvanted M2e-MAP alone. Conclusion M2e-MAP is an effective immunogen as ~15% of the total M2e-MAP-induced Ab response is of desired specificity. While M2e(pep-nat-specific serum Abs have an important

  10. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    DEFF Research Database (Denmark)

    Weinert, Brian T; Krishnadath, Kausilia K; Milano, Francesca

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated...... with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) to determine whether this treatment could improve the profile of tumor antigen genes expressed in these cells. In addition, the presence of MAGE-A tumor antigen protein was evaluated in the purified tumor cell lysate used...

  11. Comparison of intranasal and intramuscular ketamine-midazolam combination in cats.

    Science.gov (United States)

    Marjani, Mehdi; Akbarinejad, Vahid; Bagheri, Mohsen

    2015-03-01

    The aim of the present study was to compare intranasal (INS) and intramuscular (IM) routes of administration of a ketamine-midazolam combination in cats. Randomized block design. Twelve healthy mixed breed cats (six males and six females). The drug combination was ketamine (14 mg kg(-1) ) and midazolam (0.5 mg kg(-1) ). In the IM group, drugs were injected into quadratus femoris muscle; in the INS. group, the combination dropped equally into the two nostrils. Pulse and respiratory rates, peripheral haemoglobin oxygen saturation (SpO2 ) and rectal temperature were monitored before and at intervals after drug administration. Time to onset and duration of sedation and, during recovery to head up, sternal recumbency and recovery were recorded. There were no significant differences between the groups in any time measured except for recovery to sternal recumbency, where time was lower in the INS than in the IM (p = 0.034). Respiratory rate was greater in the INS than in the IM group (p = 0.029), but there was no difference between groups in other physiological parameters. In both groups SpO2 was low before and fell further during sedation. The results substantiated that INS ketamine-midazolam can produce effective sedation in cats. Intranasal (INS) administration of ketamine-midazolam is atraumatic, and its use may avoid the pain of injection of ketamine combinations when this drug is used to induce sedation in cats. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  12. Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1-2 Co-Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens.

    Science.gov (United States)

    Song, Li; Xiong, Dan; Song, Hongqin; Wu, Lili; Zhang, Meihua; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2017-01-01

    Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine. Mice immunized intranasally with HA1-2-fliC and HA1-2-PEI showed higher HA1-2-specific immunoglobulin (Ig)G and IgA titers in serum, nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation and proliferation and the number of HA1-2-specific interferon (IFN)-γ- and interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and PEI groups; in the latter, there were more cells secreting IL-4 than IFN-γ, suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and PEI induced Th2-biased responses, consistent with the serum antibody isotype pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a chicken model. The results showed that chickens receiving fliC and PEI adjuvant vaccine exhibited robust immune responses leading to a significant reduction in viral loads of throat and cloaca compared to chickens receiving only HA1-2. These findings provide a basis for the development of H7N9 influenza HA1-2 mucosal subunit vaccines.

  13. Iatrogenic Cushing’s Syndrome Following Short-Term Intranasal Steroid Use

    Science.gov (United States)

    Dutta, Deep; KS, Shivaprasad; Ghosh, Sujoy; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2012-01-01

    Cushing’s syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. In this paper, we present the case of a child who developed CS after intranasal application of combined moxifloxacin-dexamethasone eye drops for epistaxis for a period of 3 months. CS caused by ocular preparations of steroids has not been reported previously. This case report highlights the fact that even eye drops can contain high doses of steroids and can lead to CS especially in children and especially if used intranasally. Ocular steroid drops should not be used intranasally. To minimize gastrointestinal absorption and therefore the risk of CS, nasal sprays should be preferred over nasal drops for intranasal steroid application.Key words: Cushing’s syndrome, eye drops, dexamethasone, epistaxis Conflict of interest:None declared. PMID:22985615

  14. How influenza vaccination policy may affect vaccine logistics.

    Science.gov (United States)

    Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T; Welling, Joel S; Norman, Bryan A; Connor, Diana L; Chen, Sheng-I; Slayton, Rachel B; Laosiritaworn, Yongjua; Wateska, Angela R; Wisniewski, Stephen R; Lee, Bruce Y

    2012-06-22

    When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. We Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand. A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time-frame from 1 to 6 months decreases these bottlenecks. Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Use of Direct Otoscope for Intranasal Examination After Dacryocystorhinostomy.

    Science.gov (United States)

    Yazici, Bulent; Sabur, Huri; Orucov, Nesimi

    2016-01-01

    To evaluate whether the use of a direct otoscope in the nose is an effective method to observe the nasolacrimal anastomosis site after dacryocystorhinostomy. In 75 eyes undergoing external dacryocystorhinostomy, the lacrimal irrigation test was performed and fluorescein solution was instilled in the conjunctival sac. After applying topical anesthetics and decongestant, a direct otoscope was inserted in the middle meatus and directed toward the medial canthus. In 69 eyes (92%), intranasal lacrimal examination with the otoscope could be performed. In 6 eyes (8%), the otoscope could not be adequately advanced in the nose because of middle meatal stenosis (n = 5 eyes) or intolerance to the intranasal examination (n = 1). In 66 (96%) of 69 eyes, concordant with the results of the lacrimal irrigation test, the presence or absence of fluorescein dye flow in the nose was observed. In this examination, the main features that were useful in locating the anastomotic area were (1) the use of fluorescein dye, (2) motility of the nasal mucosa that was synchronized with eyelid movements, (3) appearance of mucosal hole or internal orifice in the nasal wall, and (4) dye or air-fluid bubble emergence upon blinking or finger pressure over the sac region. Direct otoscope can be effectively used in the nose for examining the nasolacrimal anastomosis in patients undergoing dacryocystorhinostomy.

  16. Therapy of respiratory viral infections with intranasal siRNAs.

    Science.gov (United States)

    Barik, Sailen; Lu, Patrick

    2015-01-01

    Chemically synthesized short interfering RNA (siRNA) has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) (two Paramyxoviruses), and influenza virus (an Orthomyxovirus). As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of single intranasal siRNA against RSV, we now offer two new strategies: (1) second-generation siRNAs, used against the paramyxoviral RNA polymerase large subunit (L), (2) siRNA cocktail with a novel transfection reagent, used against influenza virus. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (a) modified 19-27 nt-long double-stranded siRNAs are functional in the lung, (b) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, (c) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent, (d) cocktail of multiple siRNAs can be highly effective against multiple viral strains and subtypes.

  17. Evaluation of Intranasal Midazolam as an Anesthetic Premedication in Preschool Children

    Directory of Open Access Journals (Sweden)

    Sh Behdad

    2005-10-01

    Full Text Available Introduction: Preoperative psycho emotional preparation of patients is one of the principle purposes of anesthesia which can be achieved by administration of premedications. Children should receive premedication before entering the operating room due to their dependence on parents and the fear and anxiety of separation from parents. Different drugs are administered for this purpose, but considering children's sensitivity, it is wise to use the most effective and comfortable medication with least side effects. Midazolam is a rapid onset, short acting and water soluble benzodiazapine which can be administered by oral, intravenous, intramuscular, rectal or intranasal routes. The purpose of this study was to evaluate the result of intranasal midazolam administration (0.2 mg/kg as a premedication in children aged 2-6 years.( Min dose and enough time Methods: In this randomized prospective study, 100 children aged between 2-6 years old in class ASA 1 and candidates of surgery were divided into two groups; case and control. The control group received several nasal drops of normal saline, while the case group received 0.2 mg/kg nasal midazolam 20 minutes before anesthesia induction. Results: Twenty minutes after administration of the nasal drops, 14% in the control group and 68% in the case group were alert and calm. (P value=0.0 . Mask acceptance during induction of anesthesia in control and case group was 14%and 72%, respectively (P value >0.00 The recovery time in the case group was longer (P value >0.5, but no complications (nausea, vomiting, respiratory and cardiovascular problems were seen in either group. Conclusion: Nasal midazolam with its anxiolytic, tranquilizing effects and no respiratory or cardiovascular complications is a safe drug and being better than parenteral drugs is acceptable by children.

  18. Endocine™, N3OA and N3OASq; three mucosal adjuvants that enhance the immune response to nasal influenza vaccination.

    Directory of Open Access Journals (Sweden)

    Tina Falkeborn

    Full Text Available Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

  19. Adolescent Vaccines: Latest Recommendations, Addressing Barriers, and Improving Vaccine Rates.

    Science.gov (United States)

    Rose, Kathleen C

    2017-07-01

    The Advisory Committee on Immunization Practices recommends that the Tdap, HPV, and meningitis vaccines be administered to youth beginning between the ages of 11 and 12. The school nurse, knowledgeable about vaccine schedules and the rationale for the schedules, is in a unique position to advocate for all adolescent vaccines and their timely administration through addressing parent-guardian concerns and supporting other healthcare providers in completing the adolescent vaccines. This article reviews current recommendations for adolescent vaccinations and the actions needed to improve vaccination rates with a focus on Human Papillomavirus vaccine, the vaccine with the lowest completion rates among this age group. Additionally, school nurses are introduced to Middle School Health Starts Here, a program for school nurses designed to address the whole child as students progress from 5th grade to middle school. Public policy issues including school mandates, along with possible barriers to vaccine completion in adolescents, are discussed.

  20. Green revolution vaccines, edible vaccines

    African Journals Online (AJOL)

    Admin

    Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular pathogen for which the immune system has been primed (Arntzen, 1997). The release of vaccine is.

  1. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  2. Polio Vaccine

    Science.gov (United States)

    ... IBS) Home Family Health Infants and Toddlers Polio Vaccine Polio Vaccine Share Print What is polio? Poliomyelitis (polio) is ... each year. Fortunately, the use of the polio vaccine has made the disease very rare in most ...

  3. Measles Vaccination

    Science.gov (United States)

    ... World Health Organization Pan American Health Organization Measles Vaccination Pronounced (MEE-zills) Recommend on Facebook Tweet Share ... also be up to date on their MMR vaccination. The MMR vaccine is very safe and effective. ...

  4. Intranasal immunization of baculovirus displayed hemagglutinin confers complete protection against mouse adapted highly pathogenic H7N7 reassortant influenza virus.

    Directory of Open Access Journals (Sweden)

    Subaschandrabose Rajesh Kumar

    Full Text Available BACKGROUND: Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA. The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n. or subcutaneously (s.c. with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs. CONCLUSION: Our results indicated that protection from high pathogenic H7N7 (NL/219/03 virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections.

  5. Comparison of culture, single and multiplex real-time PCR for detection of Sabin poliovirus shedding in recently vaccinated Indian children.

    Science.gov (United States)

    Giri, Sidhartha; Rajan, Anand K; Kumar, Nirmal; Dhanapal, Pavithra; Venkatesan, Jayalakshmi; Iturriza-Gomara, Miren; Taniuchi, Mami; John, Jacob; Abraham, Asha Mary; Kang, Gagandeep

    2017-08-01

    Although, culture is considered the gold standard for poliovirus detection from stool samples, real-time PCR has emerged as a faster and more sensitive alternative. Detection of poliovirus from the stool of recently vaccinated children by culture, single and multiplex real-time PCR was compared. Of the 80 samples tested, 55 (68.75%) were positive by culture compared to 61 (76.25%) and 60 (75%) samples by the single and one step multiplex real-time PCR assays respectively. Real-time PCR (singleplex and multiplex) is more sensitive than culture for poliovirus detection in stool, although the difference was not statistically significant. © 2017 Wiley Periodicals, Inc.

  6. Underutilization of Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Marshall K. Cheney

    2013-04-01

    Full Text Available Yearly influenza vaccination continues to be underutilized by those who would most benefit from it. The Health Belief Model was used to explain differences in beliefs about influenza vaccination among at-risk individuals resistant to influenza vaccination. Survey data were collected from 74 members of at-risk groups who were not vaccinated for influenza during the previous flu season. Accepting individuals were more likely to perceive flu as a threat to health and perceive access barriers, and cues to action were the most important influence on whether they plan to get vaccinated. In comparison, resistant individuals did not feel threatened by the flu, access barriers were not a problem, and they did not respond favorably to cues to action. Perceived threat, perceived access barriers, and cues to action were significantly associated with plans to be vaccinated for influenza in the next flu season. Participants who saw influenza as a threat to their health had 5.4 times the odds of planning to be vaccinated than those who did not. Participants reporting barriers to accessing influenza vaccination had 7.5 times the odds of reporting plans to be vaccinated. Those responding positively to cues to action had 12.2 times the odds of planning to be vaccinated in the next flu season than those who did not. Accepting and resistant individuals have significant differences in their beliefs, which require different intervention strategies to increase vaccination rates. These findings provide important information to researchers and practitioners working to increase influenza vaccination rates.

  7. Humidification of inspired oxygen is increased with pre-nasal cannula, compared to intranasal cannula.

    Science.gov (United States)

    Dellweg, Dominic; Wenze, Markus; Hoehn, Ekkehard; Bourgund, Olaf; Haidl, Peter

    2013-08-01

    Oxygen therapy is usually combined with a humidification device, to prevent mucosal dryness. Depending on the cannula design, oxygen can be administered pre- or intra-nasally (administration of oxygen in front of the nasal ostia vs cannula system inside the nasal vestibulum). The impact of cannula design on intra-nasal humidity, however, has not been investigated to date. First, to develop a system, that samples air from the nasal cavity and analyzes the humidity of these samples. Second, to investigate nasal humidity during pre-nasal and intra-nasal oxygen application, with and without humidification. We first developed and validated a sampling and analysis system to measure humidity from air samples. By means of this system we measured inspiratory air samples from 12 subjects who received nasal oxygen with an intra-nasal and pre-nasal cannula at different flows, with and without humidification. The sampling and analysis system showed good correlation to a standard hygrometer within the tested humidity range (r = 0.99, P humidification (P = .001, P humidification. With the addition of humidification we observed no significant change in humidity at any flow, and independent of pre- or intranasal oxygen administration. Pre-nasal administration of dry oxygen achieves levels of intranasal humidity similar to those achieved by intranasal administration in combination with a bubble through humidifier. Pre-nasal oxygen simplifies application and may reduce therapy cost.

  8. Intranasal fentanyl for pain control: current status with a focus on patient considerations

    Directory of Open Access Journals (Sweden)

    Eric Prommer

    2011-03-01

    Full Text Available Eric Prommer, Lisa ThompsonDivision of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USAAbstract: Of several newer delivery systems under development and investigation for the administration of opioids, the intranasal route has received a substantial amount of attention. Intranasal administration is a convenient form of delivery that is applicable to several opioids. It has the potential for self-administration, combined with a rapid onset of action, allowing for patient-controlled analgesia. In clinical practice, intranasal administration has been found to be a reliable drug delivery method that is familiar to patients. Intranasal opioids have proven to be useful in both in-hospital and out-of-hospital pain management settings. Fentanyl, a highly lipophilic step 3 opioid, has been evaluated for intranasal administration. The purpose of this review is to examine the role of the nasal route of opioid administration and examine the evidence base for the use of fentanyl intranasally.Keywords: fentanyl, intranasal, pain, breakthrough pain

  9. Detection and differentiation of field and vaccine strains of canine distemper virus using reverse transcription followed by nested real time PCR (RT-nqPCR) and RFLP analysis.

    Science.gov (United States)

    Fischer, Cristine Dossin Bastos; Ikuta, Nilo; Canal, Cláudio Wageck; Makiejczuk, Aline; Allgayer, Mariangela da Costa; Cardoso, Cristine Hoffmeister; Lehmann, Fernanda Kieling; Fonseca, André Salvador Kazantzi; Lunge, Vagner Ricardo

    2013-12-01

    Canine distemper virus (CDV) is the cause of a severe and highly contagious disease in dogs. Practical diagnosis of canine distemper based on clinical signs and laboratory tests are required to confirm CDV infection. The present study aimed to develop a molecular assay to detect and differentiate field and vaccine CDV strains. Reverse transcription followed by nested real time polymerase chain reaction (RT-nqPCR) was developed, which exhibited analytical specificity (all the samples from healthy dogs and other canine infectious agents were not incorrectly detected) and sensitivity (all replicates of a vaccine strain were positive up to the 3125-fold dilution - 10(0.7) TCID50). RT-nqPCR was validated for CDV detection on different clinical samples (blood, urine, rectal and conjunctival swabs) of 103 animals suspected to have distemper. A total of 53 animals were found to be positive based on RT-nqPCR in at least one clinical sample. Blood resulted in more positive samples (50 out of 53, 94.3%), followed by urine (44/53, 83.0%), rectal (38/53, 71%) and conjunctival (27/53, 50.9%) swabs. A commercial immunochromatography (IC) assay had detected CDV in only 30 conjunctival samples of these positive dogs. Nucleoprotein (NC) gene sequencing of 25 samples demonstrated that 23 of them were closer to other Brazilian field strains and the remaining two to vaccine strains. A single nucleotide sequences difference, which creates an Msp I restriction enzyme digestion, was used to differentiate between field and vaccine CDV strains by restriction fragment length polymorphism (RFLP) analysis. The complete assay was more sensitive than was IC for the detection of CDV. Blood was the more frequently positive specimen and the addition of a restriction enzyme step allowed the differentiation of vaccine and Brazilian field strains. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype heterologous classical swine fever virus challenge.

    Science.gov (United States)

    Madera, Rachel; Gong, Wenjie; Wang, Lihua; Burakova, Yulia; Lleellish, Karen; Galliher-Beckley, Amy; Nietfeld, Jerome; Henningson, Jamie; Jia, Kaimin; Li, Ping; Bai, Jianfa; Schlup, John; McVey, Scott; Tu, Changchun; Shi, Jishu

    2016-09-09

    Classical swine fever (CSF) or hog cholera is a highly contagious swine viral disease. CSF endemic countries have to use routine vaccination with modified live virus (MLV) vaccines to prevent and control CSF. However, it is impossible to serologically differentiate MLV vaccinated pigs from those infected with CSF virus (CSFV). The aim of this study is to develop a one-dose E2-subunit vaccine that can provide protection against CSFV challenge. We hypothesize that a vaccine consisting of a suitable adjuvant and recombinant E2 with natural conformation may induce a similar level of protection as the MLV vaccine. Our experimental vaccine KNB-E2 was formulated with the recombinant E2 protein (Genotype 1.1) expressed by insect cells and an oil-in-water emulsion based adjuvant. 10 pigs (3 weeks old, 5 pigs/group) were immunized intramuscularly with one dose or two doses (3 weeks apart) KNB-E2, and 10 more control pigs were administered normal saline solution only. Two weeks after the second vaccination, all KNB-E2 vaccinated pigs and 5 control pigs were challenged with 5 × 10(5) TCID50 CSFV Honduras/1997 (Genotype 1.3, 1 ml intramuscular, 1 ml intranasal). It was found that while control pigs infected with CSFV stopped growing and developed high fever (>40 °C), high level CSFV load in blood and nasal fluid, and severe leukopenia 3-14 days post challenge, all KNB-E2 vaccinated pigs continued to grow as control pigs without CSFV exposure, did not show any fever, had low or undetectable level of CSFV in blood and nasal fluid. At the time of CSFV challenge, only pigs immunized with KNB-E2 developed high levels of E2-specific antibodies and anti-CSFV neutralizing antibodies. Our studies provide direct evidence that pigs immunized with one dose KNB-E2 can be protected clinically from CSFV challenge. This protection is likely mediated by high levels of E2-specific and anti-CSFV neutralizing antibodies.

  11. Evaluation of the Sedative Effects of Diazepam, Midazolam, and Xylazine After Intranasal Administration in Juvenile Ostriches ( Struthio camelus ).

    Science.gov (United States)

    Araghi, Mostafa; Azizi, Saeed; Vesal, Nasser; Dalir-Naghade, Bahram

    2016-09-01

    The sedative effects of diazepam, midazolam, and xylazine after intranasal administration were evaluated in 72 (36 male and 36 female) juvenile healthy ostriches ( Struthio camelus ), weighing 50-61 kg and aged 4-5 months. The birds were randomly divided into 3 groups (n = 24), then each group was further subdivided to 4 subgroups (n = 6). For each drug, 4 different doses were chosen and the total calculated dose was equally administered into either naris of the individual bird. The appropriate dose of each drug to produce standing chemical restraint or sternal recumbency was evaluated based on the onset time, the duration of maximum effect, and the duration of sedation. Midazolam showed significantly shorter onset time (2.9 ± 1.2 minutes) compared with xylazine (4.4 ± 1 minute) and diazepam (4.3 ± 0.4 minutes). Longer duration of sedation was also achieved with midazolam compared with xylazine and diazepam. Moderate sedation was achieved with diazepam (0.8 mg/kg), midazolam (0.4 mg/kg), and xylazine (2 mg/kg) for standing chemical restraint, with the maximum duration effects of 7.0 ± 1.4, 17.7 ± 4.1, and 9.2 ± 2.5 minutes, respectively. Deep sedation was also achieved with midazolam (0.8 mg/kg) and xylazine (4 mg/kg), with sternal recumbency duration of 21.7 ± 4.9 and 13.5 ± 2.6 minutes, respectively. The results of the present study show that intranasal administration can be an effective route for delivery of sedatives in juvenile ostriches. Intranasal midazolam and xylazine could be suggested for standing chemical restraint or inducing sternal recumbency in juvenile ostriches.

  12. Intranasal location and immunohistochemical characterization of the equine olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Alexandra Kupke

    2016-10-01

    Full Text Available The olfactory epithelium (OE is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system (CNS. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g. Borna disease virus (BoDV, equine herpesvirus 1 (EHV-1, hendra virus, influenza virus, rabies virus, vesicular stomatitis virus (VSV can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g. horses would help to underscore transferability of rodent models. Analysis of the complete noses of 5 adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein (OMP and doublecortin (DCX expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen (PCNA and tropomyosin receptor kinase A (TrkA was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine type a and b were

  13. Use of Intranasal Naloxone by Basic Life Support Providers.

    Science.gov (United States)

    Weiner, Scott G; Mitchell, Patricia M; Temin, Elizabeth S; Langlois, Breanne K; Dyer, K Sophia

    2017-01-01

    Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or

  14. Vaccines: Shaping global health.

    Science.gov (United States)

    Pagliusi, Sonia; Ting, Ching-Chia; Lobos, Fernando

    2017-03-14

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines' access, and of the importance of new public-private partnerships. Copyright © 2017.

  15. H5N1 vaccine-specific B cell responses in ferrets primed with live attenuated seasonal influenza vaccines.

    Directory of Open Access Journals (Sweden)

    Xing Cheng

    Full Text Available Live attenuated influenza H5N1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza A virus infection (Suguitan et al., Plos Medicine, e360:1541, 2006. However, the preexisting influenza heterosubtypic immunity on live attenuated H5N1 vaccine induced immune response has not been evaluated.Primary and recall B cell responses to live attenuated H5N1 vaccine viruses were examined using a sensitive antigen-specific B cell ELISpot assay to investigate the effect of preexisting heterosubtypic influenza immunity on the development of H5N1-specific B cell immune responses in ferrets. Live attenuated H5N1 A/Hong Kong/213/03 and A/Vietnam/1203/04 vaccine viruses induced measurable H5-specific IgM and IgG secreting B cells after intranasal vaccination. However, H5-specific IgG secreting cells were detected significantly earlier and at a greater frequency after H5N1 inoculation in ferrets previously primed with trivalent live attenuated influenza (H1N1, H3N2 and B vaccine. Priming studies further revealed that the more rapid B cell responses to H5 resulted from cross-reactive B cell immunity to the hemagglutinin H1 protein. Moreover, vaccination with the H1N1 vaccine virus was able to induce protective responses capable of limiting replication of the H5N1 vaccine virus to a level comparable with prior vaccination with the H5N1 vaccine virus without affecting H5N1 vaccine virus induced antibody response.The findings indicate that previous vaccination with seasonal influenza vaccine may accelerate onset of immunity by an H5N1 ca vaccine and the heterosubtypic immunity may be beneficial for pandemic preparedness.

  16. Timing of plasmid cytokine (IL-2/Ig) administration affects HIV-1 vaccine immunogenicity in HIV-seronegative subjects.

    Science.gov (United States)

    Baden, Lindsey R; Blattner, William A; Morgan, Cecilia; Huang, Yunda; Defawe, Olivier D; Sobieszczyk, Magdalena E; Kochar, Nidhi; Tomaras, Georgia D; McElrath, M Juliana; Russell, Nina; Brandariz, Kara; Cardinali, Massimo; Graham, Barney S; Barouch, Dan H; Dolin, Raphael

    2011-11-15

    To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig). This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4), or adjuvant given 2 days after vaccine (group T5). No significant differences in adverse events were observed between treatment groups. Cellular immune responses to envelope protein EnvA peptides were detected by interferon (IFN) γ and IL-2 enzyme-linked immunospot (ELISPOT) assays in 50% and 40% of subjects, respectively, in T4, and in 100% and 80% in T5. The median responses for groups T4 and T5, respectively, were 90 and 193 spot-forming cells (SFCs)/10⁶ peripheral blood mononuclear cells (P = .004; T4 vs T5) for the IL-2 ELISPOT assay and 103 and 380 SFCs/10⁶ PBMCs (P = .003; T4 vs T5) for the IFN-γ ELISPOT assay. A trend to more durable cellular immune responses in T5 was observed at 1 year (T5 vs T4/D; P = .07). Higher anti-Env antibody responses were detected with T5 than with T4. Plasmid IL-2/Ig significantly increased immune responses when administered 2 days after the DNA vaccine, compared with simultaneous administration. These observations have important implications for the development of cytokine augmentation strategies. NCT00069030.

  17. Intranasal Tooth - An Ectopic Eruption of Mesiodens in Nasal Cavity: A Case Report and Review

    Directory of Open Access Journals (Sweden)

    R Guru Prasad

    2011-01-01

    Full Text Available An intranasal tooth (INT is an ectopic tooth erupting into the nasal cavity. It is a rare clinical entity. Ectopic and supernumerary teeth may be present in many regions of maxillofacial skeleton. Ectopic teeth maybe supernumerary, deciduous or permanent. The clinical manifestations of intranasal tooth are quite variable and they may cause a variety of symptoms and complications. Their clinical and radiographic presentations are classical, posing little challenge to the diagnostician. The identification of such teeth can be important since they have potential to cause considerable morbidity. Here, we describe a case of intranasal tooth along with possible etiopathogenesis, clinical and radiographic features, differential diagnosis, potential complications and treatment modalities.

  18. Nasal saline or intranasal corticosteroids to treat allergic rhinitis in children

    Science.gov (United States)

    Madison, Stefani; Brown, Elizabeth Aubrey; Franklin, Rachel; Wickersham, Elizabeth A.; McCarthy, Laine H.

    2016-01-01

    Clinical Question In pediatric populations, is nasal saline irrigation as effective as intranasal corticosteroids at relieving allergic rhinitis symptoms? Answer No. Intranasal steroids are more effective than nasal saline alone to reduce symptoms of allergic rhinitis (AR) in children. Combination therapy further improves symptom reduction. Level of Evidence for the Answer B Search Terms Allergic Rhinitis, Nasal Saline, Nasal corticosteroids, children younger than age 18. Date Search Was Conducted August and September 2014, October 2015. Inclusion Criteria Meta-analyses, randomized controlled trials, systematic reviews, cohort studies, nasal spray, hypertonic saline solution, nasal lavage, rhinitis, intranasal administration, nasal saline, human, English language. Exclusion Criteria Antihistamines, Adults, Articles older than 2008 PMID:27328556

  19. Clinical Question: Nasal saline or intranasal corticosteroids to treat allergic rhinitis in children.

    Science.gov (United States)

    Madison, Stefani; Brown, Elizabeth Aubrey; Franklin, Rachel; Wickersham, Elizabeth A; McCarthy, Laine H

    2016-01-01

    In pediatric populations, is nasal saline irrigation as effective as intranasal corticosteroids at relieving allergic rhinitis symptoms? No. Intranasal steroids are more effective than nasal saline alone to reduce symptoms of allergic rhinitis (AR) in children. Combination therapy further improves symptom reduction. LEVEL OF EVIDENCE FOR THE ANSWER: B SEARCH TERMS: Allergic Rhinitis, Nasal Saline, Nasal corticosteroids, children younger than age 18. DATE SEARCH WAS CONDUCTED: August and September 2014, October 2015. Meta-analyses, randomized controlled trials, systematic reviews, cohort studies, nasal spray, hypertonic saline solution, nasal lavage, rhinitis, intranasal administration, nasal saline, human, English language. Antihistamines, Adults, Articles older than 2008.

  20. Get the shot or do the time: A moral defense of coerced anti-drug vaccinations given to criminal offenders

    OpenAIRE

    Wichmann, Søren Sofus

    2013-01-01

    In this thesis I defend giving drug addicted persons who are convicted of a crime the choice between an anti-drug vaccine and prison. My claim is that, should such a vaccine be developed, there would be no good moral reasons not to make such an offer. To support this claim I discuss and reject a series of objections to it. The objections are grouped in three different types; objections to paternalism, objections from theories of penal justice and objections from the rights of prisoners. Which...

  1. Formulation and kinetic modeling of curcumin loaded intranasal mucoadhesive microemulsion

    Directory of Open Access Journals (Sweden)

    B Mikesh Patel

    2012-01-01

    Full Text Available It is a challenge to develop the optimum dosage form of poorly water-soluble drugs and to target them due to limited bioavailability, intra and inter subject variability. In this investigation, mucoadhesive microemulsion of curcumin was developed by water titration method taking biocompatible components for intranasal delivery and was characterized. Nasal ciliotoxicity studies were carried out using excised sheep nasal mucosa. in vitro release studies of formulations and PDS were performed. Labrafil M 1944 CS based microemulsion was transparent, stable and nasal non-ciliotoxic having particle size 12.32±0.81nm (PdI=0.223 and from kinetic modeling, the release was found to be Fickian diffusion for mucoadhesive microemulsion.

  2. Aerosolized adenovirus-vectored vaccine as an alternative vaccine delivery method

    Directory of Open Access Journals (Sweden)

    Roy Chad J

    2011-11-01

    Full Text Available Abstract Conventional parenteral injection of vaccines is limited in its ability to induce locally-produced immune responses in the respiratory tract, and has logistical disadvantages in widespread vaccine administration. Recent studies suggest that intranasal delivery or vaccination in the respiratory tract with recombinant viral vectors can enhance immunogenicity and protection against respiratory diseases such as influenza and tuberculosis, and can offer more broad-based generalized protection by eliciting durable mucosal immune responses. Controlled aerosolization is a method to minimize vaccine particle size and ensure delivery to the lower respiratory tract. Here, we characterize the dynamics of aerosolization and show the effects of vaccine concentration on particle size, vector viability, and the actual delivered dose of an aerosolized adenoviral vector. In addition, we demonstrate that aerosol delivery of a recombinant adenoviral vaccine encoding H1N1 hemagglutinin is immunogenic and protects ferrets against homologous viral challenge. Overall, aerosol delivery offers comparable protection to intramuscular injection, and represents an attractive vaccine delivery method for broad-based immunization campaigns.

  3. Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Yuanhui [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); He, Jinsheng, E-mail: jshhe@bjtu.edu.cn [College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Zheng, Xianxian [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wu, Qiang [Department of Pathology, Anhui Medical University, Hefei, Anhui, 230032 (China); Zhang, Mei; Wang, Xiaobo [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wang, Yan [Department of Pathology, Anhui Medical University, Hefei, Anhui, 230032 (China); Xie, Can; Tang, Qian; Wei, Wei [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wang, Min; Song, Jingdong; Qu, Jianguo [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); Zhang, Ying; Wang, Xin [College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); Hong, Tao [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China)

    2009-04-17

    Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection.

  4. DNA Vaccines

    Indian Academy of Sciences (India)

    DNA vaccine, immune response, antibodies, infectious diseases. GENERAL I ARTICLE. DNA Vaccines. P N Rangarajan. History of Vaccine Development. The year 1996 marked the 200th anniversary of the first vaccine developed against smallpox by Edward Jenner. In the now- famous 1796 experiment, Jenner scratched ...

  5. Vaccination, seizures and 'vaccine damage'.

    Science.gov (United States)

    Brown, Natasha J; Berkovic, Samuel F; Scheffer, Ingrid E

    2007-04-01

    Concerns about the safety of vaccination have plagued the community, with reduction in vaccine uptake resulting in increased risk of epidemics. Vaccination has been implicated in the cause of febrile seizures, 'vaccine encephalopathy' and autistic spectrum disorders. Evaluation of alleged associations is complicated by evolution in the vaccination field. This review focuses on the risk of seizures following vaccination and the alleged associations of vaccination with vaccine encephalopathy and also with autism spectrum disorders. Over the last decade the introduction of new vaccines such as the acellular pertussis vaccine has produced a reduction in seizures following vaccination, the outcome of which was benign even with older vaccines. New evidence emerged in 2006 showing that cases of alleged 'vaccine encephalopathy' are due to mutations within a sodium channel gene. The weight of epidemiological evidence does not support a relationship between vaccination and childhood epileptic encephalopathies or autism spectrum disorders. Vaccines are safer than ever before, but the challenge remains to convey this message to society in such a way that produces change in attitudes to vaccination and subsequent increase in vaccine coverage.

  6. DNA VACCINES

    OpenAIRE

    Aksu, Burak

    2016-01-01

    Traditionally, protection against infectious diseases has relied on the use of attenuated or killed vaccines. However, many such vaccines are inadequate for reason of efficacy, safety, and cost effectiveness. Live-attenuated vaccines may be immunosuppressive, cause disease if not attenuated sufficiently, or provide limited immunity if too much attenuated. A major concern regarding the use of live vaccines is the possibility of outgrowth of more virulent organisms. Killed vaccines are often un...

  7. Hepatitis Vaccines

    OpenAIRE

    Sina Ogholikhan; Kathleen B. Schwarz

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  8. The Impact of Order Set Use on Pneumococcal Vaccination at the Time of Admission and at the Time of Discharge for Adult Patients in an Acute Inpatient Setting

    Science.gov (United States)

    Mathew, Rekha

    2012-01-01

    Background: Pneumococcal vaccination (PV) is important as Streptococcus pneumoniae accounts for one third of all hospitalizations for community-acquired pneumonia. In 2009, 1.1 million people in the U.S. were hospitalized with pneumonia and more than 50,000 people died from the disease. The Centers for Disease Control and Prevention recommend that…

  9. Effect of combination vaccines on completion and compliance of childhood vaccinations in the United States.

    Science.gov (United States)

    Kurosky, Samantha K; Davis, Keith L; Krishnarajah, Girishanthy

    2017-11-02

    Vaccination at age-appropriate intervals increases protection against morbidity and mortality; however, compliance rates among children remain low partly due to a complicated vaccination schedule. Use of combination vaccines reduces the number of injections per visit; however, there is limited evidence quantifying the effect of combination vaccines on vaccination rates. To examine how combination vaccines impact childhood completion (receipt of recommended doses) and compliance (receipt of age-appropriate vaccinations) rates, this study analyzed vaccination data from the 2012 National Immunization Survey (NIS), a nationally representative cross-sectional survey of caregivers of children aged 24 to 35 months in the United States. Vaccines were categorized as combination or single antigen. Vaccine completion was measured at ages 8, 18, and 24 months. Vaccine compliance and time undervaccinated were measured at 24 months. Children who received at least 1 combination vaccine (86%) had a higher completion rate (69%) and compliance with the full vaccine series (4:3:1:3:3:1:4 series) at 24 months (24%) than those who received only single-antigen vaccines (50% and 13%, respectively). Receipt of combination vaccine was associated with an increased likelihood of completing all recommended vaccinations at 24 months (odds ratio [OR] = 2.5; P vaccinations at age-appropriate times (OR = 2.2; P vaccines were associated with improved completion and compliance and should be encouraged among children who are undervaccinated or who received single-antigen vaccines only.

  10. Intranasal epidermoid cyst causing upper airway obstruction in three brachycephalic dogs.

    Science.gov (United States)

    Murgia, D; Pivetta, M; Bowlt, K; Volmer, C; Holloway, A; Dennis, R

    2014-08-01

    This case report describes three brachycephalic dogs with intranasal epidermoid cysts that were causing additional upper airway obstruction. Although epidermoid cysts have been described in several locations in dogs, to the authors' knowledge intranasal epidermoid cysts have not been previously reported. All dogs had mucopurulent to haemorrhagic nasal discharge. Magnetic resonance imaging of the head revealed the presence of unilateral or bilateral intranasal cystic lesions obstructing the nasal cavities partially or completely, with atrophy of the ipsilateral nasal turbinates. The cystic lesions were surgically excised in all dogs using a modified lateral alveolar mucosal approach to the affected nasal cavity. Aerobic, anaerobic and fungal culture of the cystic contents were negative and histology of the excised tissue was consistent with a benign intranasal epidermoid cyst in each dog. Upper airway obstruction was clinically improved in two dogs. © 2014 British Small Animal Veterinary Association.

  11. Influence of intranasal and carotid cooling on cerebral temperature balance and oxygenation

    DEFF Research Database (Denmark)

    Nybo, Lars; Wanscher, Michael; Secher, Niels H.

    2014-01-01

    The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood temperat......The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood...... temperatures were measured to assess the cerebral heat balance and corresponding paired blood samples were obtained to evaluate cerebral metabolism and oxygenation at rest, following 60 min of intranasal cooling, 5 min of nasal ventilation, and 15 min with carotid cooling. Intranasal cooling induced a parallel...

  12. Intranasal phototherapy versus azelastine in the treatment of seasonal allergic rhinitis.

    Science.gov (United States)

    Albu, Silviu; Baschir, Sorin

    2013-10-01

    It has been suggested that intranasal phototherapy represents an alternative choice in the treatment of seasonal allergic rhinitis (SAR). Our aim was to compare the efficacy of intranasal phototherapy with that of azelastine in patients with SAR. Seventy seven patients were randomly assigned to the two treatment groups: Group A (phototherapy) and Group B (azelastine). Subjective and objective outcomes were represented by changes in Total Nasal Symptom Score (TNSS), Quality of life scores (Rhinoconjunctivitis Quality of Life Questionnaire - RQLQ), and nasal resistance. The study demonstrated that both azelastine and intranasal phototherapy are able to significantly improve TNSS, including individual nasal symptoms. Nevertheless, phototherapy reduced nasal obstruction better than azelastine (p=0.038). Both treatments were highly effective in improving RQLQ scores overall and in seven separate domains. Whether intranasal phototheraphy will be a standard treatment of SAR or not should be appraised in future studies and clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Effect of an intranasal conrticosteroid on exercide induced bronchocostriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, E.T.; Leeuwen, J.C. van; Brand, P.L.; Duiverman, E.J.; de Jongh, Franciscus H.C.; Thio, B.J.; Driessen, J.M.

    2012-01-01

    Rationale: Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a

  14. Cushing's syndrome, growth impairment, and occult adrenal suppression associated with intranasal steroids.

    Science.gov (United States)

    Perry, R J; Findlay, C A; Donaldson, M D C

    2002-07-01

    We have previously described iatrogenic Cushing's syndrome secondary to intranasal steroids. This report further highlights the potential deleterious effects of intranasal steroids. Nine cases (including the original two cases) are reviewed to show the varied clinical manifestations of adrenal suppression caused by intranasal steroids. Four presented with Cushing's syndrome, three with growth failure, while two asymptomatic patients were discovered in the course of pituitary function testing. Four children had dysmorphic syndromes--Down's, Treacher-Collins, CHARGE association, and campomelic dysplasia--reflecting the vulnerability of such children to ENT problems, together with the difficulty of interpreting steroid induced growth failure in this context. Adrenal suppression was seen not only with betamethasone but also with budesonide, beclomethasone and flunisolide nasal preparations. A careful enquiry as to the use of intranasal steroids should be routine in children presenting with unexplained growth failure or Cushing's syndrome. Particular vigilance/awareness is required in children with dysmorphic syndromes.

  15. Intranasal Immunization with Influenza Virus-Like Particles Containing Membrane-Anchored Cholera Toxin B or Ricin Toxin B Enhances Adaptive Immune Responses and Protection against an Antigenically Distinct Virus.

    Science.gov (United States)

    Ji, Xianliang; Ren, Zhiguang; Xu, Na; Meng, Lingnan; Yu, Zhijun; Feng, Na; Sang, Xiaoyu; Li, Shengnan; Li, Yuanguo; Wang, Tiecheng; Zhao, Yongkun; Wang, Hualei; Zheng, Xuexing; Jin, Hongli; Li, Nan; Yang, Songtao; Cao, Jinshan; Liu, Wensen; Gao, Yuwei; Xia, Xianzhu

    2016-04-21

    Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs) composed of the hemagglutinin (HA), neuraminidase (NA) and matrix protein (M1) of A/Changchun/01/2009 (H1N1) with or without either membrane-anchored cholera toxin B (CTB) or ricin toxin B (RTB) as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival). Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses.

  16. Intranasal Immunization with Influenza Virus-Like Particles Containing Membrane-Anchored Cholera Toxin B or Ricin Toxin B Enhances Adaptive Immune Responses and Protection against an Antigenically Distinct Virus

    Directory of Open Access Journals (Sweden)

    Xianliang Ji

    2016-04-01

    Full Text Available Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs composed of the hemagglutinin (HA, neuraminidase (NA and matrix protein (M1 of A/Changchun/01/2009 (H1N1 with or without either membrane-anchored cholera toxin B (CTB or ricin toxin B (RTB as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival. Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses.

  17. Just-in-time vaccines: Biomineralized calcium phosphate core-immunogen shell nanoparticles induce long-lasting CD8+ T cell responses in mice

    Science.gov (United States)

    Zhou, Weibin; Moguche, Albanus; Chiu, David; Murali-Krishna, Kaja; Baneyx, François

    2014-01-01

    Distributed and on-demand vaccine production could be game-changing for infectious disease treatment in the developing world by providing new therapeutic opportunities and breaking the refrigeration “cold chain”. Here, we show that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize a biocompatible adjuvant in a single step. The resulting 50 nm calcium phosphate core-immunogen shell particles are comparable to soluble protein in inducing ovalbumin-specific antibody response and class switch recombination in mice. However, single dose vaccination with nanoparticles leads to higher expansion of ovalbumin-specific CD8+ T cells upon challenge with an influenza virus bearing the ovalbumin-derived SIINFEKL peptide, and these cells produce high levels of IFN-γ. Furthermore, mice exhibit a robust antigen-specific CD8+ T cell recall response when challenged with virus 8 months post-immunization. These results underscore the promise of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines. PMID:24275478

  18. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Directory of Open Access Journals (Sweden)

    Neha Dabral

    Full Text Available Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+ and CD8(+ T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9, 10(10 and 10(11 CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11 CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  19. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Science.gov (United States)

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  20. Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies.

    Science.gov (United States)

    Walum, Hasse; Waldman, Irwin D; Young, Larry J

    2016-02-01

    Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to social cognition, including parental behavior, social bonding, and individual recognition. Taken together, these studies in humans appear to provide compelling, but sometimes bewildering, evidence for the role of OT in influencing a vast array of complex social cognitive processes in humans. In this article, we investigate to what extent the human intranasal OT literature lends support to the hypothesis that intranasal OT consistently influences a wide spectrum of social behavior in humans. We do this by considering statistical features of studies within this field, including factors like statistical power, prestudy odds, and bias. Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects. Thus, the remarkable reports that intranasal OT influences a large number of human social behaviors should be viewed with healthy skepticism, and we make recommendations to improve the reliability of human OT studies in the future. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS.

    Directory of Open Access Journals (Sweden)

    Robert A Scranton

    2011-04-01

    Full Text Available The blood brain barrier (BBB is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS, but the relative contributions are debated.In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum.This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before we are able to advance this technique into human research.

  2. Assessment of humoral and cellular-mediated immune response in chickens treated with tilmicosin, florfenicol, or enrofloxacin at the time of Newcastle disease vaccination.

    Science.gov (United States)

    Khalifeh, M S; Amawi, M M; Abu-Basha, E A; Yonis, I Bani

    2009-10-01

    The effect of tilmicosin, florfenicol, or enrofloxacin on humoral and cell-mediated immune response induced by Newcastle disease (ND) vaccination was evaluated in 20-wk-old specific-pathogen-free layer chickens. Humoral immunity was measured by detection of ND virus (NDV) antibody titer and anti-NDV IgG response using the hemagglutination inhibition (HI) test and ELISA, respectively, whereas cell-mediated immunity was evaluated by measurement of chicken interferon gamma (ChIFN-gamma) produced in splenocytes cell culture stimulated with concanavalin A, inactivated NDV antigen, or live attenuated La Sota strain using ELISA. Florfenicol hampered the ND antibody production measured by both HI and ELISA. Tilmicosin and enrofloxacin reduced the production of ND antibody in the first 3 wk after the last ND vaccination measured by HI test, which suggests that these antibiotics exert their effect mainly on the IgM isotype. The ND-vaccinated, but not treated group, showed an increase in ChIFN-gamma production after NDV antigen-specific stimulation above the nonstimulated cell culture, whereas this effect was masked in all the antibiotic-treated groups due to the stronger ChIFN-gamma production background value reported in the nonstimulated cell culture. In conclusion, our results showed, for the first time, that tilmicosin, florfenicol, or enrofloxacin reduced the humoral immune response and had beneficial effects on the cell-mediated immune response. In addition, we demonstrated that the combination of both inactivated and attenuated ND vaccine gave a strong immune response at both the humoral and cellular level.

  3. Gut-Homing Conventional Plasmablasts and CD27(-) Plasmablasts Elicited after a Short Time of Exposure to an Oral Live-Attenuated Shigella Vaccine Candidate in Humans.

    Science.gov (United States)

    Toapanta, Franklin R; Simon, Jakub K; Barry, Eileen M; Pasetti, Marcela F; Levine, Myron M; Kotloff, Karen L; Sztein, Marcelo B

    2014-01-01

    Currently, there is no licensed Shigella vaccine; however, various promising live-attenuated vaccine candidates have emerged, including CVD1208S (ΔguaBA, Δset, Δsen S. flexneri 2a), which was shown to be safe and immunogenic in Phase 1 clinical trials. Here, we report the immune responses elicited in an outpatient Phase 2 clinical trial in which subjects were vaccinated with CVD 1208S. Oral immunization with CVD 1208S elicited high anti-S. flexneri 2a LPS and IpaB antibody responses as well as an acute plasmablast (PB) infiltration in peripheral blood 7 days after immunization. PB sorted based on their expression of homing molecules confirmed that cells expressing integrin α4β7 alone or in combination with CD62L were responsible for antibody production (as measured by ELISpot). Furthermore, using high-color flow-cytometry, on day 7 after immunization, we observed the appearance of conventional PB (CPB, CD19(dim) CD20(-) CD27(+high) CD38(+high) CD3(-)), as well as a PB population that did not express CD27 (CD27(-) PB; pre-plasmablasts). The pattern of individual or simultaneous expression of homing markers (integrin α4β7, CD62L, CXCR3, and CXCR4) suggested that CPB cells homed preferentially to the inflamed gut mucosa. In contrast, ~50% CD27(-) PB cells appear to home to yet to be identified peripheral lymphoid organs or were in a transition state preceding integrin α4β7 upregulation. In sum, these observations demonstrate that strong immune responses, including distinct PB subsets with the potential to home to the gut and other secondary lymphoid organs, can be elicited after a short time of exposure to a shigella oral vaccine.

  4. Gut-Homing Conventional Plasmablasts and CD27− Plasmablasts Elicited after a Short Time of Exposure to an Oral Live-Attenuated Shigella Vaccine Candidate in Humans

    Science.gov (United States)

    Toapanta, Franklin R.; Simon, Jakub K.; Barry, Eileen M.; Pasetti, Marcela F.; Levine, Myron M.; Kotloff, Karen L.; Sztein, Marcelo B.

    2014-01-01

    Currently, there is no licensed Shigella vaccine; however, various promising live-attenuated vaccine candidates have emerged, including CVD1208S (ΔguaBA, Δset, Δsen S. flexneri 2a), which was shown to be safe and immunogenic in Phase 1 clinical trials. Here, we report the immune responses elicited in an outpatient Phase 2 clinical trial in which subjects were vaccinated with CVD 1208S. Oral immunization with CVD 1208S elicited high anti-S. flexneri 2a LPS and IpaB antibody responses as well as an acute plasmablast (PB) infiltration in peripheral blood 7 days after immunization. PB sorted based on their expression of homing molecules confirmed that cells expressing integrin α4β7 alone or in combination with CD62L were responsible for antibody production (as measured by ELISpot). Furthermore, using high-color flow-cytometry, on day 7 after immunization, we observed the appearance of conventional PB (CPB, CD19dim CD20− CD27+high CD38+high CD3−), as well as a PB population that did not express CD27 (CD27− PB; pre-plasmablasts). The pattern of individual or simultaneous expression of homing markers (integrin α4β7, CD62L, CXCR3, and CXCR4) suggested that CPB cells homed preferentially to the inflamed gut mucosa. In contrast, ~50% CD27− PB cells appear to home to yet to be identified peripheral lymphoid organs or were in a transition state preceding integrin α4β7 upregulation. In sum, these observations demonstrate that strong immune responses, including distinct PB subsets with the potential to home to the gut and other secondary lymphoid organs, can be elicited after a short time of exposure to a shigella oral vaccine. PMID:25191323

  5. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. Real-time real-world analysis of seasonal influenza vaccine effectiveness: method development and assessment of a population-based cohort in Stockholm County, Sweden, seasons 2011/12 to 2014/15.

    Science.gov (United States)

    Leval, Amy; Hergens, Maria Pia; Persson, Karin; Örtqvist, Åke

    2016-10-27

    Real-world estimates of seasonal influenza vaccine effectiveness (VE) are important for early detection of vaccine failure. We developed a method for evaluating real-time in-season vaccine effectiveness (IVE) and overall seasonal VE. In a retrospective, register-based, cohort study including all two million individuals in Stockholm County, Sweden, during the influenza seasons from 2011/12 to 2014/15, vaccination status was obtained from Stockholm's vaccine register. Main outcomes were hospitalisation or primary care visits for influenza (International Classification of Disease (ICD)-10 codes J09-J11). VE was assessed using Cox multivariate stratified and non-stratified analyses adjusting for age, sex, socioeconomic status, comorbidities and previous influenza vaccinations. Stratified analyses showed moderate VE in prevention of influenza hospitalisations among chronically ill adults ≥ 65 years in two of four seasons, and lower but still significant VE in one season; 53% (95% confidence interval (CI): 33-67) in 2012/13, 55% (95% CI: 25-73) in 2013/14 and 18% (95% CI: 3-31) in 2014/15. In conclusion, seasonal influenza vaccination was associated with substantial reductions in influenza-specific hospitalisation, particularly in adults ≥ 65 years with underlying chronic conditions. With the use of population-based patient register data on influenza-specific outcomes it will be possible to obtain real-time estimates of seasonal influenza VE. This article is copyright of The Authors, 2016.

  7. Real-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji

    OpenAIRE

    Dunne, Eileen M.; Mantanitobua, Silivia; Singh, Shalini P.; Reyburn, Rita; Tuivaga, Evelyn; Rafai, Eric; Tikoduadua, Lisi; Porter, Barbara; Satzke, Catherine; Strachan, Janet E.; Fox, Kimberly K.; Jenkins, Kylie M.; Jenney, Adam; Baro, Silo; Mulholland, E. Kim

    2016-01-01

    As part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Of 266 samples tested, pathogens were identified in 47 (17.7%). S. pneumoniae was the most co...

  8. Live, Attenuated Venezuelan Equine Encephalitis Virus Vaccine (TC83) Causes Persistent Brain Infection in Mice with Non-functional αβ T-Cells

    Science.gov (United States)

    Taylor, Katherine; Kolokoltsova, Olga; Ronca, Shannon E.; Estes, Mark; Paessler, Slobodan

    2017-01-01

    Intranasal infection with vaccine strain of Venezuelan equine encephalitis virus (TC83) caused persistent viral infection in the brains of mice without functional αβ T-cells (αβ-TCR -/-). Remarkably, viral kinetics, host response gene transcripts and symptomatic disease are similar between αβ-TCR -/- and wild-type C57BL/6 (WT) mice during acute phase of infection [0–13 days post-infection (dpi)]. While WT mice clear infectious virus in the brain by 13 dpi, αβ-TCR -/- maintain infectious virus in the brain to 92 dpi. Persistent brain infection in αβ-TCR -/- correlated with inflammatory infiltrates and elevated cytokine protein levels in the brain at later time points. Persistent brain infection of αβ-TCR -/- mice provides a novel model to study prolonged alphaviral infection as well as the effects and biomarkers of long-term viral inflammation in the brain. PMID:28184218

  9. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  10. Conventional influenza vaccines influence the performance of a universal influenza vaccine in mice.

    Science.gov (United States)

    Rowell, Janelle; Lo, Chia-Yun; Price, Graeme E; Misplon, Julia A; Epstein, Suzanne L; Garcia, Mayra

    2018-02-08

    Universal influenza vaccines are designed to protect against diverse strains of influenza virus. Preclinical testing of new vaccine candidates is usually done in naïve animals, despite intended use in the human population with its varied immune history including responses to previous vaccinations. As an approach more relevant to human use, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group was given two intranasal doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal influenza vaccine: recombinant adenoviruses expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) (A/NP + M2-rAd). Immune responses to universal vaccine antigens A/NP and M2 were assessed by ELISA and interferon-γ ELISPOT. Protection was tested by challenge with mouse-adapted A/FM/1/47 (H1N1) and monitoring for weight loss and survival. Universal vaccine performance was enhanced, inhibited or unaffected by particular prior vaccinations. Mice given Afluria IIV and LAIV had greater antibody and T-cell response to A/NP than mice without prior vaccination, providing examples of enhanced A/NP + M2-rAd performance. Though Fluvirin IIV partially inhibited, the universal vaccine still provided considerable protection unlike conventional vaccination. Fluzone IIV and DT had no effect on A/NP + M2-rAd performance. Thus our results demonstrate that universal vaccine candidate A/NP + M2-rAd was at least partially effective in mice with diverse prior histories. However, the degree of protection and nature of the immune responses may be affected by a history of conventional vaccination and suggests that performance in humans would be influenced by immune history. Published by Elsevier Ltd.

  11. Safety and Immunogenicity of a Shigella flexneri 2a Invaplex 50 Intranasal Vaccine in Adult Volunteers

    Science.gov (United States)

    2010-06-01

    intracellularly, and spread intercellularly within the colonic epithelium [7-9). Essential components in the invasion process and subsequent immunity include...specifically including rhinoplasty, nasal polyps . ulcers. or a clinically significant deviated nasal septum) or laboratory screening (CBC, serum...Shigella infections m children in a poor peri urban setting in Santiago, Chile. Amj Epidemiol1991; 134(September (6)):614-27. D. Tribble et al. I Vacdne

  12. Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application

    NARCIS (Netherlands)

    Lankelma, Jacqueline M.; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W.; Trentelman, Jos J. A.; Weehuizen, Tassili A. F.; Ersöz, Jasmin; Roelofs, Joris J. T. H.; Hovius, Joppe W.; Wiersinga, W. Joost; Bins, Adriaan D.

    2017-01-01

    Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is

  13. Next generation vaccines.

    Science.gov (United States)

    Riedmann, Eva M

    2011-07-01

    In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.

  14. A novel method to calculate the extent and amount of drug transported into CSF after intranasal administration.

    Science.gov (United States)

    Shi, Zhenqi; Zhang, Qizhi; Jiang, Xinguo

    2005-01-31

    The aim of this paper is to establish a novel method to calculate the extent and amount of drug transported to brain after administration. The cerebrospinal fluid (CSF) was chosen as the target region. The intranasal administration of meptazinol hydrochloride (MEP) was chosen as the model administration and intravenous administration was selected as reference. According to formula transform, the extent was measured by the equation of X(A)CSF, infinity/X0 = Cl(CSF) AUC(0-->infinity)CSF/X0 and the drug amount was calculated by multiplying the dose with the extent. The drug clearance in CSF (Cl(CSF)) was calculated by a method, in which a certain volume of MEP solution was injected directly into rat cistern magna and then clearance was assessed as the reciprocal of the zeroth moment of a CSF level-time curve normalized for dose. In order to testify the accurateness of the method, 14C-sucrose was chosen as reference because of its impermeable characteristic across blood-brain barrier (BBB). It was found out that the MEP concentrations in plasma and CSF after intranasal administration did not show significant difference with those after intravenous administration. However, the extent and amount of MEP transported to CSF was significantly lower compared with those to plasma after these two administrations. In conclusion, the method can be applied to measure the extent and amount of drug transported to CSF, which would be useful to evaluate brain-targeting drug delivery.

  15. Influenza Vaccines: Unmet Needs and Recent Developments

    Science.gov (United States)

    Noh, Ji Yun

    2013-01-01

    Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described. PMID:24475351

  16. Vaccinations in asplenic adults.

    Science.gov (United States)

    Hammerquist, Rhonda J; Messerschmidt, Kimberly A; Pottebaum, April A; Hellwig, Thaddaus R

    2016-05-01

    The recommended immunizations for adult asplenic patients are reviewed. Patients without a spleen are at risk of developing overwhelming postsplenectomy infections due to encapsulated organisms, mainly pneumococcal, meningococcal, and Haemophilus influenzae type b (Hib). Due to the high mortality rates associated with these infections, vaccinations are recommended as a preventive measure. It is challenging to ensure optimal immunizations in these high-risk patients due to the number of recommended vaccines, the availability of multiple formulations, and the inability to administer specific formulations at the same time, as well as differences in subsequent vaccine administration schedules. Pharmacists play a key role in recommending specific vaccines and timing for these patients in order to achieve the most robust immune response. This article reviews the specific recommendations for pneumococcal, meningococcal, Hib, and influenza vaccinations in asplenic patients. In order to prevent potentially life-threatening infections, asplenic individuals should be vaccinated against S. pneumoniae, N. meningitidis, Hib, and influenza. The optimal timing of vaccination in relation to splenectomy depends on the nature of the splenectomy. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  17. Intranasal naloxone and related strategies for opioid overdose intervention by nonmedical personnel: a review

    Directory of Open Access Journals (Sweden)

    Lewis CR

    2017-10-01

    Full Text Available Christa R Lewis,1,2 Hoa T Vo,1 Marc Fishman1,3 1Maryland Treatment Centers, Baltimore, MD, USA; 2Department of Psychology, Towson University, Towson, MD, USA; 3Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: Deaths due to prescription and illicit opioid overdose have been rising at an alarming rate, particularly in the USA. Although naloxone injection is a safe and effective treatment for opioid overdose, it is frequently unavailable in a timely manner due to legal and practical restrictions on its use by laypeople. As a result, an effort spanning decades has resulted in the development of strategies to make naloxone available for layperson or “take-home” use. This has included the development of naloxone formulations that are easier to administer for nonmedical users, such as intranasal and autoinjector intramuscular delivery systems, efforts to distribute naloxone to potentially high-impact categories of nonmedical users, as well as efforts to reduce regulatory barriers to more widespread distribution and use. Here we review the historical and current literature on the efficacy and safety of naloxone for use by nonmedical persons, provide an evidence-based discussion of the controversies regarding the safety and efficacy of different formulations of take-home naloxone, and assess the status of current efforts to increase its public distribution. Take-home naloxone is safe and effective for the treatment of opioid overdose when administered by laypeople in a community setting, shortening the time to reversal of opioid toxicity and reducing opioid-related deaths. Complementary strategies have together shown promise for increased dissemination of take-home naloxone, including 1 provision of education and training; 2 distribution to critical populations such as persons with opioid addiction, family members, and first responders; 3 reduction of prescribing barriers to access; and 4 reduction of legal

  18. Epidemic model with vaccinated age that exhibits backward bifurcation

    International Nuclear Information System (INIS)

    Yang Junyuan; Zhang Fengqin; Li Xuezhi

    2009-01-01

    Vaccination of susceptibilities is included in a transmission model for a disease that confers immunity. In this paper, interplay of vaccination strategy together with vaccine efficacy and the vaccinated age is studied. In particular, vaccine efficacy can lead to a backward bifurcation. At the same time, we also discuss an abstract formulation of the problem, and establish the well-posedness of the model.

  19. [Protective activity of Immunovac-VP-4 vaccine against avian influenza virus H5N2 administered by different methods].

    Science.gov (United States)

    Egorova, N B; Kurbatova, E A; Akhmatova, N K; Semenova, I B

    2011-01-01

    To experimentally assess protective effect of Immunovac-VP-4 vaccine against avian influenza virus H5N2. MATERIALS AND METHODS. Immunization of mice with polycomponent vaccine Immunovac-VP-4 was performed using oral or mucosal route of administration (intranasally, orally, and with combined nasal-oral method). Immunized mice were inoculated intranasally by influenza virus H5N2 adapted for mice. Survival of mice in experimental and control (intact) groups was assessed daily during 14 days. Survival and death rates of mice were determined. Levels of cytokines in sera of mice from both groups were measured by enzyme immunoassay. Half of experimental animals survived after triple subcutaneous administration of vaccine in dose 20 mcg and subsequent intranasal challenge with avian influenza virus H5N2. Single subcutaneous immunization with dose 400 mcg resulted in survival of 80 +/- 12.6% of mice after challenge. Triple intranasal and combined intranasal-oral immunization as well as after triple subcutaneous immunization resulted in survival of half of challenged mice. In control group challenge was lethal for 90 - 100% of mice. Same methods of immunization lead to increase of IL-6, IL-12, IL-15, and IFN-gamma levels. Data about significant protective effect after immunization with Immunovac-VP-4 against avian influenza virus H5N2 were obtained. Immunovac-VP-4 administered by mentioned routes activated nasal-associated lymphoid tissue providing first line defense at entry site of influenza infection, which demonstrates need to further study of this vaccine during development of strategy for non-specific prophylaxis of influenza infection.

  20. Anthrax Vaccine

    Science.gov (United States)

    ... anthrax vaccine causes long-term health problems.Independent civilian committees have not found anthrax vaccination to be ... doctor, or get the person to a doctor right away. Tell your doctor what happened, the date ...

  1. Vaccine Safety

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Vaccine Safety Note: Javascript is disabled or is not ... CDC.gov . Recommend on Facebook Tweet Share Compartir Vaccine Adverse Events Reporting System (VAERS) New website and ...

  2. Vaccine Finder

    Science.gov (United States)

    ... list . Showing availability for 6,604 locations. Influenza Vaccine Recommended for everyone greater than or equal to ... which one may be right for you! Flu Vaccines Protects again influenza, commonly called flu, a respiratory ...

  3. Development of risperidone liposomes for brain targeting through intranasal route.

    Science.gov (United States)

    Narayan, Reema; Singh, Mohan; Ranjan, OmPrakash; Nayak, Yogendra; Garg, Sanjay; Shavi, Gopal V; Nayak, Usha Y

    2016-10-15

    The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Intranasal administration of oxytocin: behavioral and clinical effects, a review.

    Science.gov (United States)

    Veening, Jan G; Olivier, Berend

    2013-09-01

    The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. 'Direct-access-pathways' from the nasal cavity have been described but many additional experiments are needed to answer a variety of open questions regarding anatomy and physiology. Among the IN-applied substances oxytocin (OT) has an extensive history. Originally applied in women for its physiological effects related to lactation and parturition, over the last decade most studies focused on their behavioral 'prosocial' effects: from social relations and 'trust' to treatment of 'autism'. Only very recently in a microdialysis study in rats and mice, the 'direct-nose-brain-pathways' of IN-OT have been investigated directly, implying that we are strongly dependent on results obtained from other IN-applied substances. Especially the possibility that IN-OT activates the 'intrinsic' OT-system in the hypothalamus as well needs further clarification. We conclude that IN-OT administration may be a promising approach to influence human communication but that the existing lack of information about the neural and physiological mechanisms involved is a serious problem for the proper understanding and interpretation of the observed effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Intranasal melanoma treated with radiation therapy in three dogs.

    Science.gov (United States)

    Davies, Owen; Spencer, Sarah; Necova, Slavomira; Holmes, Emma; Taylor, Angela; Blackwood, Laura; Lara-Garcia, Ana

    2017-12-01

    Three dogs were investigated for chronic unilateral nasal discharge. In all cases CT imaging showed an intranasal mass causing turbinate lysis and no evidence of metastasis. Cytology in cases 1 (a 14-year-old neutered male crossbreed dog) and 2 (a five-year-old neutered male German Shepherd dog) demonstrated a pleomorphic cell population with variable intracellular pigment suspicious of melanocytic neoplasia. Histopathology with immunohistochemistry (Melan-A and vimentin, plus PNL-2 in one case) confirmed the diagnosis of melanoma in all dogs. All dogs were treated with megavoltage radiotherapy using linear accelerators. Cases 1 and 3 (a nine-year-old neutered female beagle dog) received a hypofractionated (4 × 8 Gy) protocol and case 2 received a definitive (12 × 4 Gy) protocol. Complete remission was demonstrated on repeat CT scan five months after diagnosis in case 1 and seven months in case 2. Stable disease was documented on CT at four months for case 3; however, clinical signs in this dog remained controlled for 10 months in total. Case 1 died of unrelated causes five months after diagnosis, case 2 was euthanased due to the development of seizures 13 months after diagnosis, and case 3 was lost to follow-up 12 months after diagnosis. Melanoma should be considered as a rare differential diagnosis for primary nasal neoplasia in the dog and radiation therapy can be used as effective local therapy.

  6. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

  7. ROTAVIRUS VACCINES

    OpenAIRE

    Kang, G

    2006-01-01

    Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intuss...

  8. Protein conjugate polysaccharide vaccines: Challenges in development and global implementation

    Directory of Open Access Journals (Sweden)

    Manisha Nair

    2012-01-01

    Replacement by nonvaccine serotypes;capsule switching;time duration of the antibody protective effect following vaccination;costs of the vaccines, programme costs, lack of knowledge of the disease burden, and targeting population groups for vaccination.

  9. Experimental inoculation of late term pregnant sows with a field isolate of porcine reproductive and respiratory syndrome vaccine-derived virus

    DEFF Research Database (Denmark)

    Nielsen, Jens; Bøtner, Anette; Bille-Hansen, Vivi

    2002-01-01

    than 99.6% identity to the attenuated vaccine virus, originated from the lungs of a stillborn pig from a swine herd with a sudden high level of stillborn pigs and increased piglet mortality in the nursing period. Intranasal inoculation of sows with the virus isolate resulted in congenital infection......, foetal death, and preweaning pig mortality. As such, the present study showed that vaccine-derived PRRSV can cause disease in swine consistent with PRRS....

  10. Understanding vaccine hesitancy around vaccines and vaccination from a global perspective: a systematic review of published literature, 2007-2012.

    Science.gov (United States)

    Larson, Heidi J; Jarrett, Caitlin; Eckersberger, Elisabeth; Smith, David M D; Paterson, Pauline

    2014-04-17

    Vaccine "hesitancy" is an emerging term in the literature and discourse on vaccine decision-making and determinants of vaccine acceptance. It recognizes a continuum between the domains of vaccine acceptance and vaccine refusal and de-polarizes previous characterization of individuals and groups as either anti-vaccine or pro-vaccine. The primary aims of this systematic review are to: 1) identify research on vaccine hesitancy; 2) identify determinants of vaccine hesitancy in different settings including its context-specific causes, its expression and its impact; and 3) inform the development of a model for assessing determinants of vaccine hesitancy in different settings as proposed by the Strategic Advisory Group of Experts Working Group (SAGE WG) for dealing with vaccine hesitancy. A broad search strategy, built to capture multiple dimensions of public trust, confidence and hesitancy around vaccines, was applied across multiple databases. Peer-reviewed studies were selected for inclusion if they focused on childhood vaccines [≤ 7 years of age], used multivariate analyses, and were published between January 2007 and November 2012. Our results show a variety of factors as being associated with vaccine hesitancy but they do not allow for a complete classification and confirmation of their independent and relative strength of influence. Determinants of vaccine hesitancy are complex and context-specific - varying across time, place and vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. MODELING THE EFFECTS OF UPDATING THE INFLUENZA VACCINE ON THE EFFICACY OF REPEATED VACCINATION.

    Energy Technology Data Exchange (ETDEWEB)

    D. SMITH; A. LAPEDES; ET AL

    2000-11-01

    The accumulated wisdom is to update the vaccine strain to the expected epidemic strain only when there is at least a 4-fold difference [measured by the hemagglutination inhibition (HI) assay] between the current vaccine strain and the expected epidemic strain. In this study we investigate the effect, on repeat vaccines, of updating the vaccine when there is a less than 4-fold difference. Methods: Using a computer model of the immune response to repeated vaccination, we simulated updating the vaccine on a 2-fold difference and compared this to not updating the vaccine, in each case predicting the vaccine efficacy in first-time and repeat vaccines for a variety of possible epidemic strains. Results: Updating the vaccine strain on a 2-fold difference resulted in increased vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged. Conclusions: These results suggest that updating the vaccine strain on a 2-fold difference between the existing vaccine strain and the expected epidemic strain will increase vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged.

  12. Vaccination with Vesicular Stomatitis Virus-Vectored Chimeric Hemagglutinins Protects Mice against Divergent Influenza Virus Challenge Strains.

    Science.gov (United States)

    Ryder, Alex B; Nachbagauer, Raffael; Buonocore, Linda; Palese, Peter; Krammer, Florian; Rose, John K

    2015-12-16

    Seasonal influenza virus infections continue to cause significant disease each year, and there is a constant threat of the emergence of reassortant influenza strains causing a new pandemic. Available influenza vaccines are variably effective each season, are of limited scope at protecting against viruses that have undergone significant antigenic drift, and offer low protection against newly emergent pandemic strains. "Universal" influenza vaccine strategies that focus on the development of humoral immunity directed against the stalk domains of the viral hemagglutinin (HA) show promise for protecting against diverse influenza viruses. Here, we describe such a strategy that utilizes vesicular stomatitis virus (VSV) as a vector for chimeric hemagglutinin (cHA) antigens. This vaccination strategy is effective at generating HA stalk-specific, broadly cross-reactive serum antibodies by both intramuscular and intranasal routes of vaccination. We show that prime-boost vaccination strategies provide protection against both lethal homologous and heterosubtypic influenza challenge and that protection is significantly improved with intranasal vaccine administration. Additionally, we show that vaccination with VSV-cHAs generates greater stalk-specific and cross-reactive serum antibodies than does vaccination with VSV-vectored full-length HAs, confirming that cHA-based vaccination strategies are superior at generating stalk-specific humoral immunity. VSV-vectored influenza vaccines that express chimeric hemagglutinin antigens offer a novel means for protecting against widely diverging influenza viruses. Universal influenza vaccination strategies should be capable of protecting against a wide array of influenza viruses, and we have developed such an approach utilizing a single viral vector system. The potent antibody responses that these vaccines generate are shown to protect mice against lethal influenza challenges with highly divergent viruses. Notably, intranasal vaccination

  13. A DIVA vaccine for cross-protection against Salmonella.

    Science.gov (United States)

    Bearson, Bradley L; Bearson, Shawn M D; Kich, Jalusa D

    2016-03-04

    Swine are often asymptomatic carriers of Salmonella spp., a leading cause of human bacterial foodborne disease. Vaccination against Salmonella is effective for protecting animal health and enhancing food safety. However, with >2500 Salmonella serovars, current vaccines for swine offer limited cross-protection against heterologous serovars. Also, existing vaccines can interfere with surveillance programs that monitor the Salmonella status of swine herds. To overcome Salmonella vaccine limitations, we rationally designed and constructed an attenuated Salmonella enterica serovar Typhimurium vaccine (BBS 866) by deleting multiple small regulatory RNA (sRNA) genes (omrA, omrB, rybB, micA, and invR) in combination with an rfaH mutation. We vaccinated swine intranasally at 3-weeks of age with PBS (mock-vaccinated), BBS 866 or BBS 202 (S. Typhimurium rfaH, Bearson et al., Front Vet Sci 2014;1:9.) and challenged at 7-weeks of age with virulent S. Choleraesuis, a swine pathogen. Vaccination with BBS 866 enhanced protection against S. Choleraesuis by significantly limiting the duration of fever, weight loss, the levels of circulating INFγ, and the total number of swine with S. Choleraesuis septicemia. Vaccination with either BBS 866 or BBS 202 significantly reduced S. Choleraesuis colonization of both systemic (spleen and liver) and gastrointestinal (Peyer's Patch, Ileocecal lymph nodes, and cecum) tissues. Similar to our earlier report for BBS 202, the BBS 866 vaccine strain can be used in swine without compromising the differentiation of infected from vaccinated animals (DIVA). Therefore, the attenuated S. Typhimurium BBS 866 strain, containing mutations in rfaH and multiple sRNAs, addresses the limitations of current Salmonella vaccines by providing cross-protection against Salmonella serovars in swine without interfering with established monitoring programs for Salmonella surveillance. Published by Elsevier Ltd.

  14. New approaches in oral rotavirus vaccines.

    Science.gov (United States)

    Kuate Defo, Zenas; Lee, Byong

    2016-05-01

    Rotavirus is the leading cause of severe dehydrating diarrhea worldwide, and affects primarily developing nations, in large part because of the inaccessibility of vaccines and high rates of mortality present therein. At present, there exist two oral rotaviral vaccines, Rotarix™ and RotaTeq™. These vaccines are generally effective in their actions: however, associated costs often stymie their effectiveness, and they continue to be associated with a slight risk of intussusception. While different programs are being implemented worldwide to enhance vaccine distribution and monitor vaccine administration for possible intussusception in light of recent WHO recommendation, another major problem persists: that of the reduced efficacy of the existing rotaviral vaccines in developing countries over time. The development of new oral rotavirus vaccine classes - live-attenuated vaccines, virus-like particles, lactic acid bacteria-containing vaccines, combination therapy with immunoglobulins, and biodegradable polymer-encapsulated vaccines - could potentially circumvent these problems.

  15. Immune response of sows vaccinated with attenuated transmissible gastroenteritis virus (TGEV) and recombinant TGEV spike protein vaccines and protection of their suckling pigs against virulent TGEV challenge exposure.

    Science.gov (United States)

    Park, S; Sestak, K; Hodgins, D C; Shoup, D I; Ward, L A; Jackwood, D J; Saif, L J

    1998-08-01

    To compare recombinant transmissible gastroenteritis virus (TGEV) spike protein, (SP) R2-2, with attenuated live virus (ALV) vaccine in sows during late pregnancy. 13 TGEV-seronegative sows and their pigs. At prepartum weeks (PPW) 6 and 4, sows of groups 1 and 2 received ALV via the oral/intranasal (O/IN) route. At PPW 2, group-1 sows received ALV IM and group-2 sows received SPR2-2 IM. Group-3 sows received SPR2-2 IM at PPW 4 and ALV O/IN at PPW 2. Sows of group 4 (negative controls) were inoculated O/IN with mock-infected ST cell fluids at PPW 6 and 4 and IM with Sf9 cell lysates at PPW2 (n = 2), or IM with Sf9 cell lysates at PPW4 and O/IN with mock-infected ST cell fluids at PPW2 (2). Serum, colostrum, and milk samples were tested for antibody to TGEV, and a lymphoproliferative (LP) assay was done on blood mononuclear cells. Suckling pigs were challenge exposed with virulent TGEV. Sows of groups 1 and 2 had higher IgG and significantly higher antibody titers in colostrum; their pigs had significantly higher serum antibody titer. At challenge exposure of their pigs, LP responses of group-2 sows were significantly higher than those of sows in the other 3 groups. Mean pig mortality ranged from 43 (group 2) to 92% (group 4). Significant negative correlations were observed among litter mortality and sow LP response, colostral titer, and pig serum titer at time of challenge exposure. In sows vaccinated twice with attenuated live TGEV, the recombinant SPR2-2 administered IM may be comparable to ALV administered IM as a booster. Vaccination failed to provide complete protection to suckling pigs after challenge exposure.

  16. Vaccine Adverse Events: Separating Myth from Reality.

    Science.gov (United States)

    Spencer, Jeanne P; Trondsen Pawlowski, Ruth H; Thomas, Stephanie

    2017-06-15

    Vaccines are one of the most successful medical advances in modern times. Most vaccine-preventable illnesses are unfamiliar to modern parents. Because of this, parents are increasingly questioning the necessity of immunizing their children, especially because no vaccine is completely free of adverse effects or the risk of complications. Family physicians should be aware of the risks and benefits of recommended immunizations. Thimerosal is currently used only in multidose vials of influenza vaccine, and exposure through vaccines is not associated with adverse neurologic outcomes. The measles, mumps, and rubella vaccine is not associated with autism. Vaccines are associated with local reactions, such as pain and erythema. The rotavirus vaccine minimally increases the rate of intussusception, whereas other vaccines minimally increase the risk of syncope. Although immunization with the human papillomavirus vaccine is recommended for all boys and girls, vaccination rates remain low. Physicians should guide parents to credible resources if they are considering vaccine refusal. If a recommended vaccine is refused, proper documentation is essential. The Vaccine Adverse Event Reporting System and National Vaccine Injury Compensation Program track adverse events and allow compensation for documented harms from vaccinations.

  17. Effectiveness of dog rabies vaccination programmes: comparison of owner-charged and free vaccination campaigns.

    Science.gov (United States)

    Durr, S; Mindekem, R; Kaninga, Y; Doumagoum Moto, D; Meltzer, M I; Vounatsou, P; Zinsstag, J

    2009-11-01

    We investigated the percentage of dogs that could be vaccinated against rabies by conducting a pilot campaign in N'Djaména, Chad. Owners were charged US$4.13 per dog vaccinated, and 24% of all dogs in the three city districts covered by the campaign were vaccinated. Total campaign costs were US$7623, resulting in an average of US$19.40 per vaccinated dog. This is five times more expensive than the cost per animal vaccinated during a previous free vaccination campaign for dog-owners, conducted in the same districts. The free campaign, which vaccinated 2605 more dogs than this campaign, cost an additional US$1.45 per extra dog vaccinated. Campaigns in which owners are charged for vaccinations result in lower vaccination rates than in free campaigns. Public health officials can use these results when evaluating the costs and benefits of subsidizing dog rabies vaccination programmes.

  18. College women, HPV genotyping and sexual behavior before HPV vaccination: Results from samples stored for a long time.

    Science.gov (United States)

    Herrera-Ortiz, Antonia; Conde-Glez, Carlos J; Olamendi-Portugal, Ma Leonidez; García-Cisneros, Santa; Plett-Torres, Tanya; Sánchez-Alemán, Miguel A

    HPV is the sexually transmitted agent most common among young people, like college students. The aim of study was to associate sexual behavior characteristics of women with HPV, detected in genital samples taken before the introduction of the HPV vaccine. Female students during 2001-2005 donated genital samples and the samples were re-analyzed in 2013 for HPV genotyping by RT-PCR. The frozen storage of the students' genital samples allowed the detection of HPV DNA and its genotyping after years of sample collection. HPV prevalence was 22%, HPV16 3.9%, and HPV18 1.1%. Age, multiple sexual partners and the partner's age at first sexual intercourse were significantly associated to HPV. Students with ≥ 3 sexual partners and who did not use condom had 12.8 higher odds of being HPV positive. These results made possible the analysis of HPV prevalence changes, before HPV vaccine introduction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Conservation of HIV-1 T cell epitopes across time and clades: validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine.

    Science.gov (United States)

    Levitz, Lauren; Koita, Ousmane A; Sangare, Kotou; Ardito, Matthew T; Boyle, Christine M; Rozehnal, John; Tounkara, Karamoko; Dao, Sounkalo M; Koné, Youssouf; Koty, Zoumana; Buus, Soren; Moise, Leonard; Martin, William D; De Groot, Anne S

    2012-12-14

    HIV genomic sequence variability has complicated efforts to generate an effective globally relevant vaccine. Regions of the viral genome conserved in sequence and across time may represent the "Achilles' heel" of HIV. In this study, highly conserved T-cell epitopes were selected using immunoinformatics tools combining HLA-A2 supertype binding predictions with relative global conservation. Analysis performed in 2002 on 10,803 HIV-1 sequences, and again in 2009, on 43,822 sequences, yielded 38 HLA-A2 epitopes. These epitopes were experimentally validated for HLA binding and immunogenicity with PBMCs from HIV-infected patients in Providence, Rhode Island, and/or Bamako, Mali. Thirty-five (92%) stimulated an IFNγ response in PBMCs from at least one subject. Eleven of fourteen peptides (79%) were confirmed as HLA-A2 epitopes in both locations. Validation of these HLA-A2 epitopes conserved across time, clades, and geography supports the hypothesis that such epitopes could provide effective coverage of virus diversity and would be appropriate for inclusion in a globally relevant HIV vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women.

    Science.gov (United States)

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-04-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value.

  1. Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides.

    Science.gov (United States)

    Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-01-10

    Intranasal administration is considered as an alternative route to enable effective drug delivery to the central nervous system (CNS) by bypassing the blood-brain barrier. Several reports have proved that macromolecules can be transferred directly from the nasal cavity to the brain. However, strategies to enhance the delivery of macromolecules from the nasal cavity to CNS are needed because of their low delivery efficiencies via this route in general. We hypothesized that the delivery of biopharmaceuticals to the brain parenchyma can be facilitated by increasing the uptake of drugs by the nasal epithelium including supporting and neuronal cells to maximize the potentiality of the intranasal pathway. To test this hypothesis, the CNS-related model peptide insulin was intranasally coadministered with the cell-penetrating peptide (CPP) penetratin to mice. As a result, insulin coadministered with l- or d-penetratin reached the distal regions of the brain from the nasal cavity, including the cerebral cortex, cerebellum, and brain stem. In particular, d-penetratin could intranasally deliver insulin to the brain with a reduced risk of systemic insulin exposure. Thus, the results obtained in this study suggested that CPPs are potential tools for the brain delivery of peptide- and protein-based pharmaceuticals via intranasal administration. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.

    Science.gov (United States)

    Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R

    2017-09-01

    Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

  3. Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy.

    Science.gov (United States)

    Kurdoglu, Mertihan; Yildirim, Mulazim; Kurdoglu, Zehra; Erdem, Ahmet; Erdem, Mehmet; Bilgihan, Ayse; Goktas, Bulent

    2011-08-01

    To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk. The study was conducted with 44 voluntary postmenopausal women. In group I (n = 15), the patients were treated with only intranasal estradiol (300 μg/day estradiol hemihydrate). In group II (n = 11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n = 18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment. Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p > 0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p < 0.05). Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.

  4. ROLE OF INTRANASAL STEROIDAL SPRAY IN SEASONAL ALLERGIC RHINITIS WITH OCULAR SYMPTOMS

    Directory of Open Access Journals (Sweden)

    Vineel Muppidi

    2017-06-01

    Full Text Available BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus, tearing (epiphora and redness (erythema because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

  5. [Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial].

    Science.gov (United States)

    Linares Segovia, B; García Cuevas, M A; Ramírez Casillas, I L; Guerrero Romero, J F; Botello Buenrostro, I; Monroy Torres, R; Ramírez Gómez, X S

    2014-10-01

    Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  6. Iatrogenic Cushing's Syndrome Due to Intranasal Usage of Ophthalmic Dexamethasone: A Case Report.

    Science.gov (United States)

    Orton, Sarah; Censani, Marisa

    2016-05-01

    Iatrogenic Cushing's syndrome (ICS) is caused by exogenous corticosteroid administration with suppression of the hypothalamic-pituitary-adrenal axis. It has been commonly described with oral and topical steroid use, but scarce reports have documented intranasal steroid usage as the etiology in infancy. In this article, we describe a case of a 4-month-old infant who developed ICS after 6 weeks of intranasal dexamethasone ophthalmic solution administration for nasal obstruction. To our knowledge, this is the youngest patient reported with ICS due to intranasal use of a prescribed dose of an ophthalmic steroid. His hypothalamic-pituitary-adrenal axis recovered fully 4.5 months after steroid discontinuation. Because of the small body surface area and supine position during administration, infants are particularly susceptible to ICS. Given that intranasal steroids are commonly prescribed to infants and children for a variety of diagnoses, this case highlights the risks inherent in the use of intranasal steroid drops, particularly in young infants, for both adrenal suppression and linear growth deceleration, even with short-term use. Close monitoring of these patients' height and weight should occur while on steroid treatment, with every effort made to decrease or discontinue steroid use when possible. Copyright © 2016 by the American Academy of Pediatrics.

  7. Comparison of desmopressin (DDAVP tablet and intranasal spray in the treatment of central diabetes insipidus

    Directory of Open Access Journals (Sweden)

    "Bagher Larijani

    2005-07-01

    Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

  8. FLU VACCINATION

    CERN Document Server

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  9. Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs.

    Science.gov (United States)

    Thomas, Milton; Wang, Zhao; Sreenivasan, Chithra C; Hause, Ben M; Gourapura J Renukaradhya; Li, Feng; Francis, David H; Kaushik, Radhey S; Khatri, Mahesh

    2015-01-15

    Swine influenza is widely prevalent in swine herds in North America and Europe causing enormous economic losses and a public health threat. Pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. Current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. In this study, we evaluated the protective efficacy of an intranasal Poly I:C adjuvanted UV inactivated bivalent swine influenza vaccine consisting of Swine/OH/24366/07 H1N1 and Swine/CO/99 H3N2, referred as PAV, in maternal antibody positive pigs against an antigenic variant and a heterologous swine influenza virus challenge. Groups of three-week-old commercial-grade pigs were immunized intranasally with PAV or a commercial vaccine (CV) twice at 2 weeks intervals. Three weeks after the second immunization, pigs were challenged with the antigenic variant Swine/MN/08 H1N1 (MN08) and the heterologous Swine/NC/10 H1N2 (NC10) influenza virus. Antibodies in serum and respiratory tract, lung lesions, virus shedding in nasal secretions and virus load in lungs were assessed. Intranasal administration of PAV induced challenge viruses specific-hemagglutination inhibition- and IgG antibodies in the serum and IgA and IgG antibodies in the respiratory tract. Importantly, intranasal administration of PAV provided protection against the antigenic variant MN08 and the heterologous NC10 swine influenza viruses as evidenced by significant reductions in lung virus load, gross lung lesions and significantly reduced shedding of challenge viruses in nasal secretions. These results indicate that Poly I:C or its homologues may be effective as vaccine adjuvants capable of generating cross-protective immunity against antigenic variants/heterologous swine influenza viruses in pigs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Gut-homing conventional plasmablasts and CD27- plasmablasts elicited after a short time exposure to an oral live attenuated Shigella vaccine candidate in humans

    Directory of Open Access Journals (Sweden)

    Franklin R. Toapanta

    2014-08-01

    Full Text Available Currently, there is no licensed Shigella vaccine; however, various promising live attenuated vaccine candidates have emerged, including CVD1208S (ΔguaBA, Δset, Δsen S. flexneri 2a, which was shown to be safe and immunogenic in Phase 1 clinical trials. Here we report the immune responses elicited in an outpatient Phase 2 clinical trial in which subjects were vaccinated with CVD 1208S. Oral immunization with CVD 1208S elicited high anti-S. flexneri 2a LPS and IpaB antibody responses, as well as an acute plasmablast (PB infiltration in peripheral blood 7 days after immunization. PB sorted based on their expression of homing molecules confirmed that cells expressing integrin α4β7 alone or in combination with CD62L were responsible for antibody production (as measured by ELISpot. Furthermore, using high-color flow-cytometry, on day 7 after immunization, we observed the appearance of conventional PB (CPB, CD19dim CD20- CD27+high CD38+high CD3-, as well as a PB population that did not express CD27 (CD27- PB; pre-plasmablasts. The pattern of individual or simultaneous expression of homing markers (integrin α4β7, CD62L, CXCR3 and CXCR4 suggested that CPB cells homed preferentially to the inflamed gut mucosa. In contrast, ~50% CD27- PB cells appear to home to yet to be identified peripheral lymphoid organs or were in a transition state preceding integrin α4β7 upregulation. In sum, these observations demonstrate that strong immune responses, including distinct PB subsets with the potential to home to the gut and other secondary lymphoid organs, can be elicited after a short time of exposure to a shigella oral

  11. Application of real-time global media monitoring and 'derived questions' for enhancing communication by regulatory bodies: the case of human papillomavirus vaccines.

    Science.gov (United States)

    Bahri, Priya; Fogd, Julianna; Morales, Daniel; Kurz, Xavier

    2017-05-02

    The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating 'derived questions'. The evaluation was performed through the validation of the predictive capacity of these questions against journalists' queries, review of the EMA's public statement and feedback from EU regulators. A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective

  12. Proteliposome-derived Cochleate as an immunomodulator for nasal vaccine.

    Science.gov (United States)

    Pérez, Oliver; Bracho, Gustavo; Lastre, Miriam; Zayas, Caridad; González, Domingo; Gil, Danay; del Campo, Judith; Acevedo, Reinaldo; Taboada, Carlos; Rodríguez, Tamara; Fajardo, María E; Sierra, Gustavo; Campa, Concepción; Mora, Nestor; Barberá, Ramón; Solís, Rosa L

    2006-04-12

    Proteoliposome (PL) has been recently used as a protective intramuscular (i.m.) anti-meningococcal BC vaccine. It induces a preferential Th 1 type of immune response. Nevertheless, mucosal protection is mainly mediated by IgA antibody response, which is not usually induced by i.m. vaccination route. IgA antibody production needs the stimulation of Th3 subpopulation, which is also related to the induction of small dose tolerance. We hypothesized that PL-derived Cochleate can induce a specific mucosal IgA and systemic IgG antibody responses. We could show that mice immunized with two or three intranasal doses of PL-derived Cochleate developed significantly increased levels of local anti PL IgA and systemic IgG antibody responses. Thus, our results suggest that PL-derived Cochleate can be used as a promising immunomodulator and delivery system for the development of mucosal, particularly nasal vaccines.

  13. Childhood Vaccination Against Seasonal Influenza to Reduce the Overall Burden of Disease: Ethical Perspectives.

    Science.gov (United States)

    Martakis, Kyriakos; Thangavelu, Kruthika; Schröder-Bäck, Peter

    2017-07-11

    Introduction Childhood immunisation against seasonal influenza promises to reduce the burden of disease through herd immunity. The option of intranasal vaccination seemed to offer a more acceptable vaccination for children, as they are perceived to be less invasive. Yet, intranasal vaccines have been recently proven not to be as effective as presumed. In Germany, contradictory recommendations of the Standing Committee on Vaccination (STIKO) first, to use and then, in October 2016, not use these vaccines have been issued for the 2016-2017 season, whereas recommendations not to use them were already issued in the USA (CDC, ACIP). This controversy spurs the discussion of immunisation programmes for children again. Despite studies discussing the effectiveness of a comprehensive immunisation programme targeting children also in the German and wider European context, an accompanying ethical discussion is missing. Methodology We discuss several policy options from different key ethical perspectives that are widely used in public health: if seasonal influenza vaccination should be intensively offered to or even made mandatory for children to decrease the societal burden of the disease. Results Various ethical perspectives reflect the question how to balance individual autonomy, personal benefit and population benefit differently. Discussion A convincing justification for suggestions on immunisation policies has to balance norms anchored in different ethical theories. There are good reasons to offer immunisation programmes against seasonal influenza to children, using a voluntary, possibly incentive-based approach. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder.

    Science.gov (United States)

    Alcorn, Joseph L; Rathnayaka, Nuvan; Swann, Alan C; Moeller, F Gerard; Lane, Scott D

    2015-12-01

    The oxytocin receptor is important in several domains of social behavior, and administration of oxytocin modulates social responding in several mammalian species, including humans. Oxytocin has both therapeutic and scientific potential for elucidating the neural and behavioral mechanisms governing social behavior. In the present study, operationally-defined aggressive behavior of six males with Antisocial Personality Disorder (ASPD) was measured following acute intranasal oxytocin dosing (12, 24, and 48 international units) and placebo, using a well-validated laboratory task of human aggression (Point-Subtraction Aggression Paradigm, or PSAP). The PSAP provides participants with concurrently available monetary-earning and operationally-defined aggressive response options, maintained by fixed ratio schedules of consequences. Shifts in response rates and inter-response time (IRT) distributions were observed on the aggressive response option following oxytocin doses, relative to placebo. Few changes were observed in monetary-reinforced responding. However, across participants the direction and magnitude of changes in aggressive responding were not systematically related to dose. No trends were observed between psychometric or physiological data and oxytocin dosing or aggressive behavior. While this report is to our knowledge the first to examine the acute effects of oxytocin in this population at high risk for violence and other forms of antisocial behavior, several limitations in the experimental design and the results cast the study as a preliminary report. Strategies for more extensive future projects are discussed.

  15. Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Lisa A Parr

    2014-09-01

    Full Text Available There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD. One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN OT or Placebo (saline. Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces or nonsocial (banana/cage locks stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of socially-reinforced learning, monkeys’ performed significantly better when reinforced with social versus nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

  16. Beninese vaccination clinic

    OpenAIRE

    Linda Sun

    2017-01-01

    This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

  17. Beninese vaccination clinic

    Directory of Open Access Journals (Sweden)

    Linda Sun

    2017-04-01

    Full Text Available This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

  18. IS IT NECESSARY TO VACCINATE CHILDREN AGAINST HEPATITIS A ROUTINELY IN PRESENT TIME? THE EVALUATION OF RESULTS OF SUCH STRATEGY OF HEPATITIS A VACCINE PROPHYLAXIS IN SELECTED REGIONS OF THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    I. V. Shakhgildian

    2011-01-01

    Full Text Available Abstract. Data about efficacy of conducting of routine vaccination of children against Hepatitis A are presented in the article. The results of realization such strategy of vaccine prevention of Hepatitis A in selected regions of Russian Federation are evaluated. The perspectives of using this experience in other regions of the country is discussed.

  19. A randomized, double-blind, controlled trial evaluating the effect of intranasal insulin on neurocognitive function in euthymic patients with bipolar disorder.

    Science.gov (United States)

    McIntyre, Roger S; Soczynska, Joanna K; Woldeyohannes, Hanna O; Miranda, Andrew; Vaccarino, Anthony; Macqueen, Glenda; Lewis, Gary F; Kennedy, Sidney H

    2012-11-01

    Neurocognitive deficits are prevalent, persistent, and implicated as mediators of functional impairment in adults with bipolar disorder. Notwithstanding progress in the development of pharmacological treatments for various phases of bipolar disorder, no available treatment has been proven to be reliably efficacious in treating neurocognitive deficits. Emerging evidence indicates that insulin dysregulation may be pertinent to neurocognitive function. In keeping with this view, we tested the hypothesis that intranasal insulin administration would improve measures of neurocognitive performance in euthymic adults with bipolar disorder. Sixty-two adults with bipolar I/II disorder (based on the Mini International Neuropsychiatric Interview 5.0) were randomized to adjunctive intranasal insulin 40 IU q.i.d. (n = 34) or placebo (n = 28) for eight weeks. All subjects were prospectively verified to be euthymic on the basis of a total score of ≤ 3 on the seven-item Hamilton Depression Rating Scale (HAMD-7) and ≤ 7 on the 11-item Young Mania Rating Scale (YMRS) for a minimum of 28 consecutive days. Neurocognitive function and outcome was assessed with a neurocognitive battery. There were no significant between-group differences in mean age of the subjects {i.e., mean age 40 [standard deviation (SD) = 10.15] years in the insulin and 39 [SD = 10.41] in the placebo groups, respectively}. In the insulin group, n = 27 (79.4%) had bipolar I disorder, while n = 7 (21.6%) had bipolar II disorder. In the placebo group, n = 25 (89.3%) had bipolar I disorder, while n = 3 (10.7%) had bipolar II disorder. All subjects received concomitant medications; medications remained stable during study enrollment. A significant improvement versus placebo was noted with intranasal insulin therapy on executive function (i.e., Trail Making Test-Part B). Time effects were significant for most California Verbal Learning Test indices and the Process Dissociation Task-Habit Estimate, suggesting an

  20. Hepatitis Vaccines

    Science.gov (United States)

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  1. Vaccine Reduces HPV Infections in Young Men

    Science.gov (United States)

    An international randomized clinical trial has shown that the vaccine Gardasil can reduce the incidence of anogenital human papillomavirus (HPV) infections in young men 16 to 26 years of age at the time of vaccination.

  2. Modeling the effects of annual influenza vaccination

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.J.; Ackley, D.H.; Forrest, S. [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Computer Science; Perelson, A.S. [Los Alamos National Lab., NM (United States). Theoretical Div.

    1998-12-31

    Although influenza vaccine efficacy is 70--90% in young healthy first-time vaccinees, the efficacy in repeat vaccinees has varied considerably. In some studies, vaccine efficacy in repeat vaccinees was higher than in first-time vaccinees, whereas in other studies vaccine efficacy in repeat vaccinees was significantly lower than in first-time vaccinees and sometimes no higher than in unvaccinated controls. It is known that the closeness of the antigenic match between the vaccine strain and the epidemic virus is important for vaccine effectiveness. In this study the authors show that the antigenic differences between a first vaccine strain and a second vaccine strain, and between the first vaccine strain and the epidemic strain, might account for the observed variation in attack rate among two-time vaccinees.

  3. Buccal, intranasal or intravenous lorazepam for the treatment of acute convulsions in children in Malawi: An open randomized trial

    Directory of Open Access Journals (Sweden)

    Samantha Lissauer

    2015-09-01

    Conclusions: Intravenous lorazepam effectively treats most childhood seizures in this setting. Intranasal and buccal routes are less effective but may be useful in pre-hospital care or when intravenous access cannot be obtained. Further studies comparing intranasal lorazepam to other benzodiazepines, or alternative doses by a non-intravenous route are warranted.

  4. Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels-A pilot study.

    Science.gov (United States)

    Eckl-Dorna, J; Fröschl, R; Lupinek, C; Kiss, R; Gattinger, P; Marth, K; Campana, R; Mittermann, I; Blatt, K; Valent, P; Selb, R; Mayer, A; Gangl, K; Steiner, I; Gamper, J; Perkmann, T; Zieglmayer, P; Gevaert, P; Valenta, R; Niederberger, V

    2017-10-30

    Administration of the therapeutic anti-IgE antibody omalizumab to patients induces strong increases in IgE antibody levels. To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen-specific IgE in patients with birch pollen allergy. Based on the fact that intranasal allergen application induces rises of systemic allergen-specific IgE, we performed a double-blind placebo-controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen-specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen-specific IgE levels and omalizumab-IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL-4/anti-CD40-treated PBMCs from allergic patients were studied in vitro. Intranasal challenge with Bet v 1 induced increases in Bet v 1-specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen-specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL-4/anti-CD40-induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE-omalizumab complexes were observed after subcutaneous administration of omalizumab. Intranasal administration of allergen induced rises of allergen-specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen-specific IgE levels. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

  5. IS ATOMIZED INTRANASAL MIDAZOLAM A NOVEL SEDATIVE PREMEDICATION IN PAEDIATRIC PATIENTS?

    Directory of Open Access Journals (Sweden)

    Savitri D. Kabade

    2017-06-01

    Full Text Available BACKGROUND The successful conduct of anaesthesia in children depends on adequate premedication, which not only comforts the anxious child but also comforts the parents or guardians. Atomized Intranasal Midazolam is quickly absorbed through the nasal mucosa, resulting in a rapid and reliable onset of action. Clonidine has several applications in paediatric anaesthesia as a premedication and as an adjuvant in general as well as regional anaesthesia. Thus, in search of a novel premedication technique, we conducted a study to compare the effectiveness of atomized intranasal midazolam with intranasal clonidine for preoperative sedation in paediatric patients undergoing elective surgery. MATERIALS AND METHODS After obtaining Institutional Ethical Committee clearance and parent’s consent, a prospective, randomised, double-blinded clinical study was conducted in 78 children of ASA I and II, belonging to 2 - 10 years age, posted for various elective surgery. Group M (n= 39 received atomized intranasal midazolam (0.3 mg/kg and Group C (n= 39 received clonidine (4 mcg/kg instilled into both the nostrils. Sedation score (Ramsay, separation score, mask acceptance, recovery and vital parameters were recorded. Statistical analysis of data was done using IBM-SPSS version 21.0. RESULTS Mean sedation scores (± SD were higher in Group M than in Group C (at 5th minute 1.58 ± 0.55 in Group M and 1.15 ± 0.36 in Group C with P= 0.002, at 10th minute 2.34 ± 0.97 in Group M and 1.75 ± 0.71 in Group C with P= 0.008. Separation scores and mask acceptance were better with Group M than Group C. Haemodynamic parameters were similar in both the groups and no major adverse effects were noted. CONCLUSION Atomized intranasal midazolam produces superior sedation levels, child-parent separation and mask acceptance compared to intranasal clonidine in children.

  6. Sedative Effects of Intranasal Midazolam Administration in Wild Caught Blue-fronted Amazon (Amazona aestiva) and Orange-winged Amazon (Amazona amazonica) Parrots.

    Science.gov (United States)

    Schaffer, Débora P H; de Araújo, Nayone L L C; Raposo, Ana Cláudia S; Filho, Emanoel F Martins; Vieira, João Victor R; Oriá, Arianne P

    2017-09-01

    Safe and effective sedation protocols are important for chemical restraint of birds in clinical and diagnostic procedures, such as clinical evaluations, radiographic positioning, and blood collection. These protocols may reduce stress and ease the management of wild-caught birds, which are susceptible to injury or death when exposed to stressful situations. We compare the sedative effect of intranasal midazolam in wild-caught blue-fronted (Amazona aestiva) and orange-winged (Amazona amazonica) Amazon parrots. Ten adult parrots of each species (n = 20), of unknown sex, weighing 0.337 ± 0.04 (blue-fronted) and 0.390 ± 0.03 kg (orange-winged), kg were used. Midazolam (2 mg/kg) was administered intranasally and the total volume of the drug was divided equally between the 2 nostrils. Onset time and total sedation time were assessed. Satisfactory sedation for clinical evaluation was induced in all birds. Onset time and total sedation times were similar in both species: 5.36 ± 1.16 and 25.40 ± 5.72 minutes, respectively, for blue-fronted Amazons and 5.09 ± 0.89 and 27.10 ± 3.73 minutes, respectively, for orange-winged Amazons. A total of 15 animals showed absence of vocalization, with moderate muscle relaxation and wing movement upon handling, and 2 animals presented with lateral recumbence, with intense muscle relaxation and no wing movement, requiring no restraint. Three blue-fronted Amazons had no effective sedation. Intranasally administered midazolam at a dose of 2 mg/kg effectively promoted sedative effects with a short latency time and fast recovery in wild-caught parrots.

  7. Real-time RPA assay for rapid detection and differentiation of wild-type pseudorabies and gE-deleted vaccine viruses.

    Science.gov (United States)

    Wang, Jianchang; Liu, Libing; Wang, Jinfeng; Pang, Xiaoyu; Yuan, Wanzhe

    2018-02-15

    The objective of this study was to develop a dual real-time recombinase polymerase amplification (RPA) assay using exo probes for the detection and differentiation of pseudorabies virus (PRV). Specific RPA primers and probes were designed for gB and gE genes of PRV within the conserved region of viral genome. The reaction process can be completed in 20 min at 39 °C. The dual real-time RPA assay performed in the single tube was capable of specific detecting and differentiating of the wild-type PRV and gE-deleted vaccine strains, without cross-reactions with other non-targeted pig viruses. The analytical sensitivity of the assay was 10 2 copies for gB and gE genes. The dual real-time RPA demonstrated a 100% diagnostic agreement with the real-time PCR on 4 PRV strains and 37 clinical samples. Through the linear regression analysis, the R 2 value of the real-time RPA and the real-time PCR for gB and gE was 0.983 and 0.992, respectively. The dual real-time RPA assay provides an alternative useful tool for rapid, simple, and reliable detection and differentiation of PRV, especially in remote and rural areas. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Elevated Salivary Levels of Oxytocin Persist More than 7 h after Intranasal Administration

    OpenAIRE

    van IJzendoorn, Marinus H.; Bhandari, Ritu; van der Veen, Rixt; Grewen, Karen M.; Bakermans-Kranenburg, Marian J.

    2012-01-01

    We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 a.m.) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7 h in total. Oxytocin levels did not differ amon...

  9. Elevated salivary levels of oxytocin persist more than seven hours after intranasal administration

    OpenAIRE

    Marinus H. Van IJzendoorn; Ritu eBhandari; Rixt evan der Veen; Karen eGrewen; Marian J. Bakermans-Kranenburg

    2012-01-01

    We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 IU or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 AM) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7h in total.Oxytocin levels did not differ among...

  10. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  11. FLU VACCINATION

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  12. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  13. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  14. IFN-γ and TNF-α producing CD4+ T-cells in the blood after Mycoplasma hyosynoviae challenge of vaccinated pigs

    DEFF Research Database (Denmark)

    Riber, Ulla; Hansen, Mette Sif; Lauritsen, Klara Tølbøll

    In a vaccine trial against Mycoplasma hyosynoviae infection, pigs were vaccinated with formalin fixed whole-cell-antigen formulated with adjuvant DDA/TDB (SSI). Placebo pigs received adjuvant with saline. Vaccinations were performed at five and eight weeks of age, followed by an intranasal M....... hyosynoviae challenge inoculation three weeks later. Vaccination induced both antibodies and a cell-mediated immune response (CMI) in vaccinated pigs compared to placebo pigs as shown by M. hyosynoviae antigen (Ag) specific IFN-γ response in an IL-18 potentiated whole-blood IFN-γ stimulation assay (mean IFN......-γ level 1936 pg/ml vs. 82 pg/ml (p=0.0001)). A central memory T cell phenotype with polyfunctional capacity to produce all three cytokines IFN-γ, TNF-α and IL-2 has recently been linked to development of vaccine induced protection in several infections. In a subset of seven vaccinated pigs and four...

  15. Secondary Vibrio cholerae-specific cellular antibody responses following wild-type homologous challenge in people vaccinated with CVD 103-HgR live oral cholera vaccine: changes with time and lack of correlation with protection.

    Science.gov (United States)

    Losonsky, G A; Tacket, C O; Wasserman, S S; Kaper, J B; Levine, M M

    1993-02-01

    Peripheral blood immunoglobulin A antibody-secreting-cell (ASC) responses are thought to reflect the mucosal immune response to locally presented antigens. We evaluated the ASC response to cholera toxin (CT) and Inaba lipopolysaccharide (LPS) in 26 North American volunteers following immunization with a single oral dose of live attenuated Vibrio cholerae O1 vaccine strain CVD 103-HgR and again upon homologous wild-type challenge with V. cholerae classical Inaba 569B. Challenge occurred at either 7, 30, or 180 days after vaccination. The CT and LPS ASC responses of volunteers following vaccination (83 and 55%, respectively) were similar in magnitude and frequency to those of unvaccinated controls following wild-type challenge (80 and 60%, respectively [0.1 LPS ASC responses. Challenge at 6 months resulted in a heightened ASC response to LPS, confirming the existence of mucosal memory. ASC responses to CT upon challenge at 6 months were detectable but not different from that seen following primary immunization, suggesting that secondary ASC responses to different antigens from a single vaccine operate independently. In spite of these variable ASC responses, the vaccine efficacy was 100% following challenge for all vaccinees. V. cholerae-specific ASC responses following antigenic reexposure gave information on the presence of mucosal B memory cells but did not correlate with protective immunity. As such, these ASC assays will have limited usefulness for evaluating vaccine responders in vaccine field trials in cholera-endemic areas where prior V. cholerae O1 exposure is unknown.

  16. Leptospirosis vaccines

    OpenAIRE

    Jin Li; Wang Zhijun; Węgrzyn Alicja

    2007-01-01

    Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the...

  17. Combination Vaccines

    OpenAIRE

    Skibinski, David AG; Baudner, Barbara C; Singh, Manmohan; O’Hagan, Derek T

    2011-01-01

    The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of th...

  18. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  19. Live attenuated H7N7 influenza vaccine primes for a vigorous antibody response to inactivated H7N7 influenza vaccine.

    Science.gov (United States)

    Babu, Tara M; Levine, Min; Fitzgerald, Theresa; Luke, Catherine; Sangster, Mark Y; Jin, Hong; Topham, David; Katz, Jacqueline; Treanor, John; Subbarao, Kanta

    2014-11-28

    H7 influenza viruses have emerged as potential pandemic threat. We evaluated the safety and immunogenicity of two candidate H7 pandemic live attenuated influenza vaccines (pLAIV) and their ability to prime for responses to an unadjuvanted H7 pandemic inactivated influenza vaccine (pIIV). Healthy seronegative adults received two doses of A/Netherlands/219/03 (H7N7) or one dose of A/chicken/British Columbia/CN-6/04 (H7N3) pLAIV all given as 10(7.5) 50% tissue culture infective doses (TCID50) intranasally. A subset of subjects received one 45 μg dose of H7N7 pIIV containing the A/Mallard/Netherlands/12/2000 HA intramuscularly 18-24 months after pLAIV. Viral shedding was assessed by culture and real-time polymerase chain reaction (rRT-PCR), B cell responses following pLAIV were evaluated by ELISPOT and flow cytometry. Serum antibody was assessed by hemagglutination-inhibition (HAI), microneutralization (MN) and ELISA assays after each vaccine. Serum HAI or MN responses were not detected in any subject following one or two doses of either H7 pLAIV, although some subjects had detectable H7 specific B cells after vaccination. However, 10/13 subjects primed with two doses of H7N7 pLAIV responded to a subsequent dose of the homologous H7N7 pIIV with high titer HAI and MN antibody that cross-reacted with both North American and Eurasian lineage H7 viruses, including H7N9. In contrast, naïve subjects and recipients of a single dose of the mismatched H7N3 pLAIV did not develop HAI or MN antibody after pIIV. While pLAIVs did not elicit detectable serum MN or HAI antibody, strain-specific pLAIV priming established long term immune memory that was cross-reactive with other H7 influenza strains. Understanding the mechanisms underlying priming by pLAIV may aid in pandemic vaccine development. Copyright © 2014. Published by Elsevier Ltd.

  20. SAFETY AND EFFICIENCY OF INACTIVATED OF SUBUNIT INFLUENZA VACCINE AT MASS VACCINATION OF CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu.Z. Gendon

    2007-01-01

    Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.