Beals, Chan R; Railkar, Radha A; Schaeffer, Andrea K; Levin, Yotam; Kochba, Efrat; Meyer, Brian K; Evans, Robert K; Sheldon, Eric A; Lasseter, Kenneth; Lang, Nancy; Weinberg, Adriana; Canniff, Jennifer; Levin, Myron J
The licensed live, attenuated varicella-zoster virus vaccine prevents herpes zoster in adults older than 50 years. We aimed to determine whether intradermal administration of zoster vaccine could enhance vaccine immunogenicity compared with conventional needle subcutaneous administration. In this randomised, dose-ranging study, adults aged 50 years or older who had a history of varicella or who had resided in a country with endemic varicella-zoster virus infection for 30 years or more were eligible. Participants received the approved full or a 1/3 dose of zoster vaccine given subcutaneously or one of four intradermal doses (full, 1/3, 1/10, or 1/27 dose) using the MicronJet600 device. The two subcutaneous doses and the four intradermal doses were randomised (1·5:1:1:1:1:1) by computer generated sequence with randomisation stratified by age (50-59 years or 60 years or older). The primary immunogenicity endpoint was the change from baseline in IgG antibody to varicella-zoster virus-specific glycoproteins (gpELISA) measured at 6 weeks. All patients were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, number NCT01385566. Between Sept 2, 2011, and Jan 13, 2012, 224 participants were enrolled from three clinics in the USA and 223 were randomly assigned: 52 to receive the full dose subcutaneous zoster vaccine, 34 to receive the 1/3 dose subcutaneous zoster vaccine, 34 to receive the full dose intradermal zoster vaccine, 35 to receive the 1/3 dose intradermal zoster vaccine, 34 to receive the 1/10 dose intradermal zoster vaccine, and 34 to receive the 1/27 dose intradermal zoster vaccine. Full dose zoster vaccine given subcutaneously resulted in a gpELISA geometric mean fold-rise (GMFR) of 1·74 (90% CI 1·48-2·04) at 6 weeks post-vaccination compared with intradermal administration which resulted in a significantly higher gpELISA GMFR of 3·25 (2·68-3·94; pvaricella-zoster virus gpELISA antibody compared with subcutaneous
Meijer, W. J.; Wensing, A. M. J.; Bos, A. A.; Kuiphuis, J. C. F.; Hagelen, E. M. M.; Wilschut, J. C.; de Vries, M. J. T.; Riezebos-Brilman, A.
Objective: To explore the nature and severity of side effects and future preference of intradermal versus intramuscular influenza vaccination in healthcare workers. Design: Prospective cohort study. Setting: Two University Medical Centers in The Netherlands. Participants: Healthcare workers
Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W
A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Al Jarad, N; Empey, D W; Duckworth, G
BCG vaccination using the multipuncture device (the Heaf gun) is recommended in the UK for infants and very small children only. The aim of this study was to investigate the rate of conversion of the tuberculin test, the safety and acceptability of BCG vaccination using the multipuncture device and to compare it with the conventional intradermal method in schoolchildren. Schoolchildren attending schools in Tower Hamlets who were eligible for BCG vaccination were tuberculin tested using the Heaf gun. Those with grade 0-1 reaction were randomised to receive BCG vaccination using either the multipuncture or the intradermal method. The site of BCG vaccination was inspected after eight weeks for inflammatory changes and scarring. A questionnaire about pain and inflammation at the site of vaccination was completed. The Heaf test was repeated at eight weeks and its results were assessed by an examiner unaware of the results of the previous Heaf test and the method of BCG administration. The Heaf test conversion was deemed to have occurred if there was a change of at least one grade in the response. One hundred and sixty nine children (83 girls) of mean age 11.8 years completed the study, of which 81 received BCG by the multipuncture method. The Heaf test did not convert in 22 of 81 (27. 2%) receiving BCG by the multipuncture device compared with six of 88 (6.8%) who received the vaccine by the intradermal method (odds ratio 0.2, 95% confidence interval 0.07 to 0.55). The BCG scar was visible in all children who had intradermal BCG compared with 67 of 81 (81.8%) of the multipuncture group. The multipuncture method was less painful and caused fewer inflammatory changes than the intradermal method. In schoolchildren the multi-puncture device for administering BCG caused a lower rate of tuberculin conversion as measured by the Heaf test and less of an inflammatory response than the intradermal method. The method needs to be modified before it is applied on a wider scale to
Saitoh, Akihiko; Aizawa, Yuta
Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccin...
Saitoh, Akihiko; Aizawa, Yuta
Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children.
Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D
Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418
Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.
Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA
A prospective study of a low-dose (one-tenth) intradermal regimen using recombinant hepatitis B vaccine was undertaken during two consecutive years in 4th-year medical students. Eighty one per cent of the vaccinees (123/152) seroconverted with anti-HBs levels of > 10 lU/l. The lower titre of hepatitis B surface antibodies ...
A prospective study of a low-dose (one-tenth) intradermal regimen using recombinant hepatitis B vaccine was under- taken during two consecutive years in 4th-year medical stu- dents. Eightj;one per cent of the vaccinees (123/152) sero- converted with anti.HBs levels of> 10 lUll. The lower titre of hepatitis B surface ...
Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin
Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall
the skin by the bite of infected fleas and is characterized by acute painful swelling of regional lymph nodes. Progression to septicemic or secondary... mately intended for human use. All of the vaccines we investigated were developed inde- pendently, using buffers and additives that were poten...revealed positive, fluorescent intracytoplasmic granules, verifying the mate - rial was aluminum from the vaccine adjuvant (Fig. 1E inset). These results
Lemière, S.; Alaphilippe, A.; Boucher, S.; Bertagnoli, S
A study of safety of combined vaccination against myxomatosis and VHD was performed using a duly reconstituted vaccine made of a live homologous myxomatosis component SG33 strain and of an inactivated VHD component in adjuvant AG88 strain. The vaccine was administered intradermally to a representative sample of pet rabbits. A local reaction at the vaccine administration area was frequently observed from 2 to 3 days after vaccination in young animals. These local reactions were less frequently...
Coleman, Brenda L; McNeil, Shelly A; Langley, Joanne M; Halperin, Scott A; McGeer, Allison J
Vaccinating healthcare workers against influenza takes tens of thousands of hours of work annually. This study was undertaken to determine the acceptability, success rate, and time to vaccinate healthcare workers in nurse-led groups that self-vaccinated with intradermal influenza vaccine compared with nurse-administered intramuscular vaccine. Volunteer hospital workers were randomly assigned to groups that either self-administered intradermal influenza vaccine (Intanza(®)) in a nurse-led group or received nurse-administered intramuscular vaccine (Vaxigrip(®)). Research assistants timed vaccination procedures; pre- and post-injection questionnaires assessed acceptability and reactogenicity. 810 adults, 21-69 years of age, from two study sites were vaccinated: 401 self-administered the intradermal vaccine while 409 received their intramuscular vaccine from a nurse. Of those who self-administered for the first time, 98.5% were successful on their first attempt with an additional 1.5% on their second attempt. Acceptability was high: 96% were very or somewhat certain that they administered the vaccine correctly, 83% would choose intradermal influenza vaccine again and of those, 75% would choose self-administration again, if given the choice. It took 51.3-72.6s per person for the nurses to guide the groups through the self-administration process, which was significantly less time than it took to individually administer the intramuscular vaccines (93.6s). Self-administration of intradermal influenza vaccine by people working in healthcare settings is a possible alternative to nurse administered vaccinations, with nurse-led group sessions a good way of teaching the technique while being available to respond to unanticipated problems (NCT01665807). Copyright © 2015 Elsevier Ltd. All rights reserved.
Ravish, Hardanahalli S; Vijayashankar, Veena; Madhusudana, Shampur N; Sudarshan, Mysore K; Narayana, Doddabele Ha; Andanaiah, Gangaboraiah; Ashwin, Belludi Y; Rachana, Annadani R; Shamanna, Manjula
The affordability to rabies vaccine for intramuscular administration in post exposure prophylaxis is a major constraint. Therefore, in countries, where there are financial constraints, World Health Organization recommends intradermal rabies vaccination that reduces the quantity and cost of vaccination. This study was done to evaluate the safety and immunogenicity of indigenously developed rabies vaccine (VaxiRab N) in comparison to a WHO recommended rabies vaccine (Rabipur) with demonstrated efficacy when administered by intradermal route using updated Thai Red Cross regimen. Eighty-six dog bite cases were randomly given either VaxiRab N (n = 43) or Rabipur (n = 43) as post exposure prophylaxis. The rabies virus neutralizing antibody concentrations on days 14, 28, 90, and 180 were tested by modified rapid fluorescent focus inhibition test. The geometric mean RVNA concentration of both the groups were compared using t- test and was found that, P value > 0.05 on all days, thus showing no significant difference between the 2 groups. The adverse drug events were also compared using Z-test and was found to be not statistically significant (Z = 1.476, P = 0.139). In conclusion, VaxiRab N was found to be safe and effective in post exposure prophylaxis by intradermal route and was similar to the WHO recommended rabies vaccine (Rabipur) of demonstrated efficacy.
Brown, David; Fooks, Anthony R.; Schweiger, Martin
Intradermal rabies vaccine is recommended by the World Health Organisation, but not all countries, including England, follow this recommendation. A group of 12 adults in England previously given pre-exposure intradermal rabies vaccine were considered to be non-immune to rabies because their rabies antibody titres were known to be less than 0.5 IU/mL. A cohort study examined the immunizing effect of increasing the participants' cumulative dose of intradermal rabies to 2.0 IU. All patients subs...
Eblé, P L; Weerdmeester, K; van Hemert-Kluitenberg, F; Dekker, A
The aim of this study was to investigate whether intradermal (ID) vaccination against foot-and-mouth disease (FMD) is suitable as an alternative for the usually used intramuscular (IM) route. We compared vaccine efficacy in groups of pigs in which vaccine administration differed with respect to antigen payload of the vaccine, administrated volume and administration route. When compared with pigs that were IM vaccinated with a full dose vaccine with a standard antigen payload, pigs vaccinated ID with 1/10 dose of the same vaccine were equally protected against clinical disease and subclinical virus shedding. The ID vaccinated pigs were protected against virus shedding at a significant lower VN-titre as compared to IM vaccinated pigs, suggesting that immune responses other than neutralising antibodies also contributed to protection. We conclude that the ID route might be a good alternative for IM application, as ID application might induce a very efficient immunological response against FMD and, moreover, because the dose required by the ID route is lower compared to the IM route, ID application may reduce the production costs per dose of FMD vaccine markedly.
Hong, C S; Kim, C W; Park, J W
Immediate skin reactions to allergens are influenced by several factors, such as the amount of administered allergen, the level of specific IgE, releasability of mast cells and hyperresponsiveness of the target organ. For the evaluation of factors influencing immediate skin response to intradermal allergen administration, we measured the wheal size 15 min after intradermal injection of 0.01-0.02 ml of the following agents: whole-body extract of Dermatophagoides farinae, 1,000 allergy units/ml; histamine, 0.1 mg/ml, and codeine sulfate, 0.09% in saline, and determined total IgE level, specific IgE and IgG subclass antibodies to D. farinae in 53 patients with respiratory allergy. Multiple regression analysis for factors influencing wheal size after intradermal injection of D. farinae, specific IgE antibody level to D. farinae and wheal size after intradermal administration of histamine showed statistically significant results (R2 = 0.42739, p = 0.0000; R2 = 0.50243, p = 0.0185, respectively). Multiple regression analysis for factors influencing wheal size after intradermal administration in the group with high levels of specific IgE to D. farinae (RAST class 3 or more) showed that wheal size after intradermal administration of codeine was the only factor exerting a statistically significant influence (p = 0.0119). Based on the above results, we can state that immediate responses to intradermal allergen administration were influenced by the level of specific IgE and hyperresponsiveness of the target organ to histamine, but that the immediate skin allergic responses in the presence of high levels of specific IgE were partially but significantly influenced by the releasability of skin mast cells.
A. A. N. Subawa
Full Text Available Background: Rabies is a cause of death to people within 100% of Case Fatality Rate. Approximately 55.000 people died because of rabies each year, the vast majority of these deaths happen in Asia and Africa. This study aims to find out comparative immune responses of intradermal (ID and intramuscular (IM vaccination in children. Method: This was an experimental study to determine antibody response of ID and IM rabies vaccines with randomized pre and posttest control group design. ID and IM vaccination were carried out in 4 replication for each group. A number of 16 children were recruited for each group. Enzyme Linked Immunosorbent Assay (ELISA was applied to determine titers antibody on day 0, 7, 21, and 28 after vaccination. Results: This study found that titer antibody induced by ID vaccination was lower than IM vaccination. However, the different is not statistically significant in both groups (p > 0.05. Titers antibody on day 7 after vaccination were 3.08 ± 2.09 IU/ml intradermally and 4.22 ± 3.02 IU/ml intramuscularly. On day 21 and 28 after intradermal vaccination, titers antibody were 6.78 ± 3.52 IU/ml and 12.53 ± 5.92 IU/ml, respectively. Intramuscularly, antibody titers were 9.76 ± 4.86 IU/ml on day 21 and 14.98 ± 7.76 IU/ml on day 28.Conclusion: ID vaccination is safe and can be used as an alternative vaccination for rabies in human. In addition, 0, 7, 21 ID vaccination methods can be recommended for use to control rabies cases in Indonesia because that methods induce protective immune response.
Beffort, Lisa; Weiß, Christine; Fiebig, Kerstin; Jolie, Rika; Ritzmann, Mathias; Eddicks, Matthias
The present study compares the safety and efficacy of a needle-free, intradermal Mycoplasma hyopneumoniae vaccine to an intramuscular one. 420 piglets (21+3 days of age) were randomly assigned to two vaccination groups (intradermal vaccination V1 (n=138), intramuscular vaccination V2 (n=144)) and one unvaccinated control group (CG, n=138). As safety parameters clinical observations, local injection site reactions (ISR) and rectal temperatures were assessed. Average daily weight gain (ADWG) and pneumonic lung lesions (LL) were measured as efficacy parameters. ISRs were minor in V1. After both vaccinations, no adverse impact on appetite was observed and mean rectal temperatures remained within physiological range. ADWG during the fattening period was significantly higher in vaccinated groups (V1: 913.4 g, V2: 924.5 g) compared with CG (875.6 g). No differences in ADWG were observed between V1 and V2. Vaccinated pigs had a significantly reduced mean extent of LL compared with CG. V1 was superior in reducing the extent and prevalence of LL compared with V2. These results reveal that a needle-free intradermal vaccination is safe and efficacious in reducing both the prevalence and extent of lung lesions, as well as in improving performance parameters, in a farrow-to-finish farm with a late onset of M hyopneumoniae infection. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Full Text Available There is a significant gap in our fundamental understanding of early morphological and migratory changes in human Langerhans cells (LCs in response to vaccine stimulation. As the vast majority of LCs studies are conducted in small animal models, substantial interspecies variation in skin architecture and immunity must be considered when extrapolating the results to humans. This study aims to determine whether excised human skin, maintained viable in organ culture, provides a useful human model for measuring and understanding early immune response to intradermally delivered vaccine candidates. Excised human breast skin was maintained viable in air-liquid-interface organ culture. This model was used for the first time to show morphological changes in human LCs stimulated with influenza virus-like particle (VLP vaccines delivered via intradermal injection. Immunohistochemistry of epidermal sheets and skin sections showed that LCs in VLP treated skin lost their typical dendritic morphology. The cells were more dispersed throughout the epidermis, often in close proximity to the basement membrane, and appeared vertically elongated. Our data provides for increased understanding of the complex morphological, spatial and temporal changes that occur to permit LC migration through the densely packed keratinocytes of the epidermis following exposure to vaccine. Significantly, the data not only supports previous animal data but also provides new and essential evidence of host response to this vaccination strategy in the real human skin environment.
Moro, Pedro L; Harrington, Theresa; Shimabukuro, Tom; Cano, Maria; Museru, Oidda I; Menschik, David; Broder, Karen
In May 2011, the first trivalent inactivated influenza vaccine exclusively for intradermal administration (TIV-ID) was licensed in the US for adults aged 18-64 years. To characterize adverse events (AEs) after TIV-ID reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. We searched VAERS for US reports after TIV-ID among persons vaccinated from July 1, 2011-February 28, 2013. Medical records were requested for reports coded as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis. Clinicians reviewed available information and assigned a primary clinical category to each report. Empirical Bayesian data mining was used to identify disproportional AE reporting following TIV-ID. Causality was not assessed. VAERS received 466 reports after TIV-ID; 9 (1.9%) were serious, including one reported fatality in an 88-year-old vaccinee. Median age was 43 years (range 4-88 years). The most common AE categories were: 218 (46.8%) injection site reactions; 89 (19.1%) other non-infectious (comprised mainly of constitutional signs and symptoms); and 74 (15.9%) allergy. Eight reports (1.7%) of anaphylaxis were verified by the Brighton criteria or a documented physician diagnosis. Disproportional reporting was identified for three AEs: 'injection site nodule', 'injection site pruritus', and 'drug administered to patient of inappropriate age'. The findings for the first two AEs were expected. Twenty-four reports of vaccinees reported, and 14 of 24 were coded with the AE 'drug administered to patient of inappropriate age'. Review of VAERS reports did not identify any new or unexpected safety concerns after TIV-ID. Injection site reactions were the most commonly reported AEs, similar to the pre-licensure clinical trials. Use of TIV-ID in younger and older individuals outside the approved age range highlights the need for education of healthcare providers
Zhang, Suohui; Qin, Guangjiong; Wu, Yan; Gao, Yunhua; Qiu, Yuqin; Li, Fang; Xu, Bai
In vitro and in vivo permeation studies were conducted to evaluate the characteristic of percutaneous administration of high hydrophilic drug L-carnitine (LC) by Functional MicroArray (FMA) painless intradermal delivery system. In vitro study was designed to assess the effects of various skins, donor concentration and hydrogels from different carbomer derivatives on the release of LC in a Franz-type diffusion cell. The LC gel patches with carbomer 980 P were prepared and successfully applied to pharmacokinetic study of SD rats with and without FMA. Intravenous injection and oral administration were performed to support pharmacokinetic calculations and comparison of bioavailability. Enhanced delivery of LC using FMA was achieved in skin of different species in vitro studies. The 750 mg LC gel patches were applied to rats over 6 h, and approximately 27% of loaded dose was transported into rat. A 2.8-fold enhancement of absolute bioavailability for LC with FMA intradermal delivery system was observed compared with oral LC administration in vivo study. Both in vitro and in vivo studies demonstrated that the FMA intradermal delivery system can enhance the delivery and bioavailability of LC.
N. S. Budayanti
Full Text Available BackgroundThe outbreak of rabies in human in Bali-Indonesia is causing an extraordinary pressure for the government in providing adequate doses of anti-rabies vaccine for post-exposure prophylaxis (PEP. Here, we directly compare the immune response and benefit of the intradermal (ID protocol for rabies vaccine delivery with the intramuscular (IM route. Methods: Sixty health workers who were willing to participate in this study have been randomly selected and grouped into ID, IM, and control groups, each with 20 volunteers. The Thai Red Cross ID- and Zangreb IM-protocols have been applied to the respective group. The sera of the volunteers were collected at day 0, week 1, week 3, week 4, month 3, month 6, month 9, and month 12 after the first vaccination. Anti-rabies virus IgG was detected using PlateliaTM Rabies II Kit (Bio-Rad. Results: Anti-rabies IgG could be detected in the ID-group at one week. The ID-vaccine delivery induced a slightly higher maximum antibody titer compared to IM, though not statistically significant (p>0.05. ID vaccination caused less adverse reactions and produces longer lasting protective immune response. Cost minimization analysis (CMA on the provincial and national PEP data in 2009-2011 shows that the ID-delivery will reduce the total cost for a completed regimen by USD 28.5, and would have saved the Indonesian government budget approximately USD 3.6 and 4.3 million for complete regimens in Bali and Indonesia, respectively. Conclusion: The ID administration of anti-rabies vaccine induces a similar immune response compared to that of intramuscular injection. It also produces longer lasting protective immune response. It offers additional advantages of potential net cost savings as well as decreasing the pressure on vaccine availability due to the high number of dog bite cases.
Schipper, Pim; van der Maaden, Koen; Romeijn, Stefan; Oomens, Cees; Kersten, Gideon; Jiskoot, Wim; Bouwstra, Joke
The aim of this study was to investigate the depth-dependent intradermal immunogenicity of inactivated polio vaccine (IPV) delivered by depth-controlled microinjections via hollow microneedles (HMN) and to investigate antibody response enhancing effects of IPV immunization adjuvanted with CpG oligodeoxynucleotide 1826 (CpG) or cholera toxin (CT). A novel applicator for HMN was designed to permit depth- and volume-controlled microinjections. The applicator was used to immunize rats intradermally with monovalent IPV serotype 1 (IPV1) at injection depths ranging from 50 to 550 μm, or at 400 μm for CpG and CT adjuvanted immunization, which were compared to intramuscular immunization. The applicator allowed accurate microinjections into rat skin at predetermined injection depths (50-900 μm), -volumes (1-100 μL) and -rates (up to 60 μL/min) with minimal volume loss (±1-2%). HMN-mediated intradermal immunization resulted in similar IgG and virus-neutralizing antibody titers as conventional intramuscular immunization. No differences in IgG titers were observed as function of injection depth, however IgG titers were significantly increased in the CpG and CT adjuvanted groups (7-fold). Intradermal immunogenicity of IPV1 was not affected by injection depth. CpG and CT were potent adjuvants for both intradermal and intramuscular immunization, allowing effective vaccination upon a minimally-invasive single intradermal microinjection by HMN.
Mann, Jamie F S; McKay, Paul F; Fiserova, Anezka; Klein, Katja; Cope, Alethea; Rogers, Paul; Swales, Julie; Seaman, Michael S; Combadiere, Behazine; Shattock, Robin J
It is accepted that an effective prophylactic HIV-1 vaccine is likely to have the greatest impact on viral transmission rates. As previous reports have implicated DNA-priming, protein boost regimens to be efficient activators of humoral responses, we sought to optimize this regimen to further augment vaccine immunogenicity. Here we evaluated single versus concurrent intradermal (i.d.) and intramuscular (i.m.) vaccinations as a DNA-priming strategy for their abilities to elicit humoral and cellular responses against a model HIV-1 vaccine antigen, CN54-gp140. To further augment vaccine-elicited T and B cell responses, we enhanced cellular transfection with electroporation and then boosted the DNA-primed responses with homologous protein delivered subcutaneously (s.c.), intranasally (i.n.), i.m., or transcutaneously (t.c.). In mice, the concurrent priming regimen resulted in significantly elevated gamma interferon T cell responses and high-avidity antigen-specific IgG B cell responses, a hallmark of B cell maturation. Protein boosting of the concurrent DNA strategy further enhanced IgG concentrations but had little impact on T cell reactivity. Interestingly protein boosting by the subcutaneous route increased antibody avidity to a greater extent than protein boosting by either the i.m., i.n., or t.c. route, suggesting that this route may be preferential for driving B cell maturation. Using an alternative and larger animal model, the rabbit, we found the concurrent DNA-priming strategy followed by s.c. protein boosting to again be capable of eliciting high-avidity humoral responses and to also be able to neutralize HIV-1 pseudoviruses from diverse clades (clades A, B, and C). Taken together, we show that concurrent multiple-route DNA vaccinations induce strong cellular immunity, in addition to potent and high-avidity humoral immune responses. The route of vaccination has profound effects on prevailing immune responses. Due to the insufficient immunogenicity and
Tantawichien, Terapong; Sibunruang, Suda; Tantawichien, Thanphet; Angsanakul, Jaruboot; Benjavongkulchai, Maneerat; Limsuwan, Kornvika; Udomchaisakul, Piyada; Khomvilai, Sumana; Sitprija, Visith
Improved rabies pre- and post-exposure prophylaxis (PrEP and PEP) in developing countries uses an economic multi-site intradermal vaccination. To evaluate immunogenicity of chromatographically purified Vero cell vaccine (CPRV) for intradermal PrEP and PEP. The subjects received conventional PrEP with CPRV or PVRV in PrEP study or received intradermal PEP with CPRV or PVRV and rabies immunoglobulin in PEP study. All subjects who received PrEP with CPRV had protective neutralizing antibody (Nab) titers (≥0.5 IU/ml) 14 days after completing vaccination. In PEP study, Nab titers in the CPRV groups reached ≥ 0.5 IU/ml in all subjects by day 14 through day 90 after vaccination. The geometric mean titers of Nab in the CPRV groups had significantly higher titers than the PVRV group on day 14 through day 365 (p < 0.05). No serious adverse reactions were observed. CPRV is safe and immunogenic when given for intradermal PrEP and PEP.
Du, Guangsheng; Hathout, Rania M; Nasr, Maha; Nejadnik, M Reza; Tu, Jing; Koning, Roman I; Koster, Abraham J; Slütter, Bram; Kros, Alexander; Jiskoot, Wim; Bouwstra, Joke A; Mönkäre, Juha
In this study, we investigated the potential of intradermal delivery of nanoparticulate vaccines to modulate the immune response of protein antigen using hollow microneedles. Four types of nanoparticles covering a broad range of physiochemical parameters, namely poly (lactic-co-glycolic) (PLGA) nanoparticles, liposomes, mesoporous silica nanoparticles (MSNs) and gelatin nanoparticles (GNPs) were compared. The developed nanoparticles were loaded with a model antigen (ovalbumin (OVA)) with and without an adjuvant (poly(I:C)), followed by the characterization of size, zeta potential, morphology, and loading and release of antigen and adjuvant. An in-house developed hollow-microneedle applicator was used to inject nanoparticle suspensions precisely into murine skin at a depth of about 120μm. OVA/poly(I:C)-loaded nanoparticles and OVA/poly(I:C) solution elicited similarly strong total IgG and IgG1 responses. However, the co-encapsulation of OVA and poly(I:C) in nanoparticles significantly increased the IgG2a response compared to OVA/poly(I:C) solution. PLGA nanoparticles and liposomes induced stronger IgG2a responses than MSNs and GNPs, correlating with sustained release of the antigen and adjuvant and a smaller nanoparticle size. When examining cellular responses, the highest CD8(+) and CD4(+) T cell responses were induced by OVA/poly(I:C)-loaded liposomes. In conclusion, the applicator controlled hollow microneedle delivery is an excellent method for intradermal injection of nanoparticle vaccines, allowing selection of optimal nanoparticle formulations for humoral and cellular immune responses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Teunissen, M B M; Haniffa, M; Collin, M P
Dendritic cells (DC) are the key initiators and regulators of any immune response which determine the outcome of CD4(+) and CD8(+) T-cell responses. Multiple distinct DC subsets can be distinguished by location, phenotype, and function in the homeostatic and inflamed human skin. The function of steady-state cutaneous DCs or recruited inflammatory DCs is influenced by the surrounding cellular and extracellular skin microenvironment. The skin is an attractive site for vaccination given the extended local network of DCs and the easy access to the skin-draining lymph nodes to generate effector T cells and immunoglobulin-producing B cells for long-term protective immunity. In the context of intradermal vaccination we describe in this review the skin-associated immune system, the characteristics of the different skin DC subsets, the mechanism of antigen uptake and presentation, and how the properties of DCs can be manipulated. This knowledge is critical for the development of intradermal vaccine strategies and supports the concept of intradermal vaccination as a superior route to the conventional intramuscular or subcutaneous methods.
Arévalo, Maria Isabel; Escribano, Elvira; Calpena, Ana; Domenech, Josep; Queralt, Josep
We examined the time course (7 weeks) of thermal hyperalgesia and light touch allodynia in rats after intradermal administration of Mycobacterium butyricum. Nociceptive thresholds to heat and light touch were assessed. Paw edema and temperature, motor function, body weight, and propioception were also tested. Some rats developed arthritis (named AA rats) but others did not (named non-AA rats). Both groups were compared with healthy animals. Persistent hyperalgesia was found in both groups; in AA rats it appeared before clinical evidence of arthritis. Transient allodynia ocurred only after edema development and fell when edema decreased. Motor function was impaired only in AA rats. The results of this study demonstrate that hyperalgesia, but not allodynia, appeared after Mycobacterium butyricum in both groups, suggesting that changes in sensitivity were not merely the result of local hypersensitivity of the inflamed tissue, but may also be due to alterations in nociception in the central nervous system.
Chen, Mei-Chin; Huang, Shih-Fang; Lai, Kuan-Ying; Ling, Ming-Hung
This study introduces a microneedle transdermal delivery system, composed of embeddable chitosan microneedles and a poly(L-lactide-co-D,L-lactide) (PLA) supporting array, for complete and sustained delivery of encapsulated antigens to the skin. Chitosan microneedles were mounted to the top of a strong PLA supporting array, providing mechanical strength to fully insert the microneedles into the skin. When inserted into rat skin in vivo, chitosan microneedles successfully separated from the supporting array and were left within the skin for sustained drug delivery without requiring a transdermal patch. The microneedle penetration depth was approximately 600 μm (i.e. the total length of the microneedle), which is beneficial for targeted delivery of antigens to antigen-presenting cells in the epidermis and dermis. To evaluate the utility of chitosan microneedles for intradermal vaccination, ovalbumin (OVA; MW = 44.3 kDa) was used as a model antigen. When the OVA-loaded microneedles were embedded in rat skin in vivo, histological examination showed that the microneedles gradually degraded and prolonged OVA exposure at the insertion sites for up to 14 days. Compared to traditional intramuscular immunization, rats immunized by a single microneedle dose of OVA showed a significantly higher OVA-specific antibody response which lasted for at least 6 weeks. These results suggest that embeddable chitosan microneedles are a promising depot for extended delivery of encapsulated antigens to provide sustained immune stimulation and improve immunogenicity. Copyright © 2013 Elsevier Ltd. All rights reserved.
Eriksson, Fredrik; Tötterman, Thomas; Maltais, Anna-Karin; Pisa, Pavel; Yachnin, Jeffrey
We tested safety, clinical efficacy and immunogenicity of a DNA vaccine coding for rhesus prostate specific antigen (PSA) delivered by intradermal injection and skin electroporation. Fifteen patients with biochemical relapse of prostate cancer without macroscopic disease participated in this phase I study. Patients were started on a 1 month course of androgen deprivation therapy (ADT) prior to treatment. Vaccine doses ranged from 50 to 1,600 μg. Study subjects received five vaccinations at four week intervals. All patients have had at least one year of follow-up. No systemic toxicity was observed. Discomfort from electroporation did not require analgesia or topical anesthetic. No clinically significant changes in PSA kinetics were observed as all patients required antiandrogen therapy shortly after completion of the 5 months of vaccination due to rising PSA. Immunogenicity, as measured by T-cell reactivity to the modified PSA peptide and to a mix of overlapping PSA peptides representing the full length protein, was observed in some patients. All but one patient had pre-study PSA specific T-cell reactivity. ADT alone resulted in increases in T-cell reactivity in most patients. Intradermal vaccination with skin electroporation is easily performed with only minor discomfort for the patient. Patients with biochemical relapse of prostate cancer are a good model for testing immune therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.
M.G. Roukens (Guy); A.C.Th.M. Vossen (Ann); P.J. Bredenbeek (Peter); J.T. van Dissel (Jaap); L.G. Visser (Leo)
textabstractBackground:Implementation of yellow fever vaccination is currently hampered by limited supply of vaccine. An alternative route of administration with reduced amounts of vaccine but without loss of vaccine efficacy would boost vaccination programmes.Methods and Findings:A randomized,
Verreck, Frank A W; Tchilian, Elma Z; Vervenne, Richard A W; Sombroek, Claudia C; Kondova, Ivanela; Eissen, Okke A; Sommandas, Vinod; van der Werff, Nicole M; Verschoor, Ernst; Braskamp, Gerco; Bakker, Jaco; Langermans, Jan A M; Heidt, Peter J; Ottenhoff, Tom H M; van Kralingen, Klaas W; Thomas, Alan W; Beverley, Peter C L; Kocken, Clemens H M
M.bovis BCG vaccination against tuberculosis (TB) notoriously displays variable protective efficacy in different human populations. In non-human primate studies using rhesus macaques, despite efforts to standardise the model, we have also observed variable efficacy of BCG upon subsequent experimental M. tuberculosis challenge. In the present head-to-head study, we establish that the protective efficacy of standard parenteral BCG immunisation varies among different rhesus cohorts. This provides different dynamic ranges for evaluation of investigational vaccines, opportunities for identifying possible correlates of protective immunity and for determining why parenteral BCG immunisation sometimes fails. We also show that pulmonary mucosal BCG vaccination confers reduced local pathology and improves haematological and immunological parameters post-infection in animals that are not responsive to induction of protection by standard intra-dermal BCG. These results have important implications for pulmonary TB vaccination strategies in the future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Vitoriano-Souza, Juliana; Coura-Vital, Wendel; Braga, Samuel Leôncio; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; de Lana, Marta; Figueiredo Gontijo, Nelder; Marques, Marcos José; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa
In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21(+)) and both CD4(+) and CD8(+) T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4(+) T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions.
Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Vitoriano-Souza, Juliana; Coura-Vital, Wendel; Braga, Samuel Leôncio; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; de Lana, Marta; Gontijo, Nelder Figueiredo; Marques, Marcos José; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa
In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21+) and both CD4+ and CD8+ T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4+ T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions. PMID:23189161
Full Text Available This case report examined the natural course of reaction after accidental intramuscular administration of high dose Bacille Calmette-Guιrin (BCG vaccine into the anterolateral aspect of thigh of a pre-term infant as a part of routine vaccination instead of intra-dermal injection into the arm. There is no consensus on the best management of this complication, although in this case healing was prolonged but was spontaneous without anti-tubercular chemotherapy.
Warrell, Mary J.; Riddell, Anna; Yu, Ly-Mee; Phipps, Judith; Diggle, Linda; Bourhy, Hervé; Deeks, Jonathan J.; Fooks, Anthony R.; Audry, Laurent; Brookes, Sharon M.; Meslin, François-Xavier; Moxon, Richard; Pollard, Andrew J.; Warrell, David A.
Background The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Methods Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. Findings All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. Conclusions This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be
Mary J Warrell
Full Text Available The need for economical rabies post-exposure prophylaxis (PEP is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90; or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further
Vlassopoulos, D A; Arvanitis, D K; Lilis, D S; Louizou, K I; Hadjiconstantinou, V E
Intramuscular (i.m.) and Intradermal (i.d.) vaccination against hepatitis B (HB) are efficient in hemodialysis patients. We retrospectively analysed the response of 32 patients during 48 consecutive months and compared the results of the two vaccination routes using the recombinant vaccine (Engerix, SKB). Thirteen patients were vaccinated with 5 mcg i.d. every 2 weeks (total 8 doses), plus an i.m. dose on month (M) 12 (group A). Nineteen patients (group B) were vaccinated with 4 i.m. doses of 20 mcg each, on months M0, 1, 2 and 12. HB antibodies were measured on M5, M11, M13, M24, M36 and M48. An additional 20 mcg i.m. dose was given with titers below 10 mIU/ml. Seroconversion, seroprotection and antibody levels were equivalent in both groups up to M13; with the exception of seroconversion rates, a significantly different response was observed afterwards (A/B, in mIU/ml): M5: 399 +/- 107 vs 342 +/- 69, M13: 536 +/- 118 vs 673 +/- 61, M24: 278 +/- 94 vs 595 +/- 81, P=0.02, and M48: 68 +/- 29 vs 565 +/- 92, P=0.003. Early HB(S)AB levels did not correlate with those found four years later in both groups. An additional booster dose was given 8 times in 4 group A patients (1-3 doses/patient) and 3 times in 1 group B patient. Immune response to HB vaccine in hemodialysis patients is initially equivalent by both immunization routes. Late antibody titers were found significantly lower in i.d. immunization with more frequent booster doses needed.
Kulkarni, Prasad S; Sapru, Amita; D'costa, Pradeep M; Pandit, Anand; Madhusudana, Shampur N; Yajaman, Ashwin Belludi; Mangrule, Somnath; Gunale, Bhagwat; Bavdekar, Ashish R
Rabies is 100% fatal but preventable with modern vaccines and immunoglobulins. There is a huge demand for rabies vaccines in developing countries of Asia and Africa. We have developed a new purified vero cell rabies vaccine (PVRV) and evaluated its safety and immunogenicity in healthy volunteers by intramuscular (IM) and intradermal (ID) routes of vaccination. Sixty adults aged between 18 and 50 years were recruited in this actively controlled Phase I clinical study and were randomized to receive three 1 ml or 0.1 ml doses of new PVRV intramuscularly or intradermally on days 0, 7 and 21. The control group received commercially available PVRV (Verorab) by intramuscular route. Adverse events (AEs) were recorded with diary cards till day 28 post-vaccination. Immunogenicity was assessed on day 0, 7, 21 and 42 by rapid fluorescence focus inhibition test (RFFIT). In all, 116 solicited local and systemic events were reported across the three groups. Most were mild and resolved without sequelae. Also the few unsolicited events, deemed unrelated to the study vaccines, caused no problems. No significant changes in the routine laboratory parameters were found. Two doses of a vaccine elicited protective titres (≥ 0.5 IU/ml) in all subjects, the GMTs varying between 0.57 and 0.69 IU/ml on day 7, 3.07 and 3.97 IU/ml on day 21, and 6.12 and 8.52 IU/ml on day 42 post-vaccination. PVRV was well tolerated and showed good immunogenicity regardless of whether administered intramuscularly or, using a tenth of that volume, intradermally. Further studies with this new vaccine are warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.
Le Luduec, Jean-Benoît; Debeer, Sabine; Piras, Fabienne; Andréoni, Christine; Boudet, Florence; Laurent, Philippe; Kaiserlian, Dominique; Dubois, Bertrand
Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species. Copyright © 2016 Elsevier Ltd. All rights reserved.
Pakravan, Nafiseh; Mahmoudi, Elaheh; Hashemi, Seyed-Ali; Kamali, Jamal; Hajiaghayi, Reza; Rahimzadeh, Mitra; Mahmoodi, Vajiheh
Natural ingredients have been always an interesting approach to prolong youthful appearance of skin. One of the natural compounds is Kombucha tea (KT), which has been mainly used as an energy drink in Asian countries for a long time. Previous reports indicated that it has pharmaceutical and favorable wound repairing effects. The beneficial properties of KT are thought to be mainly due to the presence of fermentation products such as flavonoids and other polyphenols with inhibition of hydrolytic and oxidative enzymes and anti-inflammatory effects. These properties prompted us to study the anti-aging potential of KT and investigate its effective fraction in aged mice, METHODS: Kombucha tea was fractionated into chloroform, butanol, and ethyl acetate, and flavonoid content was determined. Young and old mice were used as control. KT ethyl acetate fraction (KEAf), which had the highest flavonoid content, was intradermally administered to old mice. Administration of KEAf significantly increased the collagen content, NAD + /NADH level, and concomitantly improved skin connective tissue abnormalities in the aged skin. No sensitivity or irritation was observed. This finding suggested that KEAf can be a suitable candidate as a cosmetic product to improve aging-related skin abnormalities and regeneration of aged skin. © 2017 Wiley Periodicals, Inc.
Launay, Odile; van der Vliet, Diane; Rosenberg, Arielle R; Michel, Marie-Louise; Piroth, Lionel; Rey, David; Colin de Verdière, Nathalie; Slama, Laurence; Martin, Karine; Lortholary, Olivier; Carrat, Fabrice
Alternative schedules more immunogenic than the standard hepatitis B vaccine regimen are needed in patients with human immunodeficiency virus 1 (HIV-1) infection. To compare the safety and immunogenicity of 4 intramuscular double-dose and 4 intradermal low-dose regimens vs the standard hepatitis B vaccine regimen. An open-label, multicenter, 1:1:1 parallel-group, randomized trial conducted between June 28, 2007, and October 23, 2008 (date of last patient visit, July 3, 2009) at 33 centers in France with patients enrolled in French National Agency for Research on AIDS and Viral Hepatitis trials in adults with HIV-1 infection who were hepatitis B virus (HBV) seronegative and having CD4 cell counts of more than 200 cells/μL. Patients were randomly assigned to receive 3 intramuscular injections of the standard dose (20 μg) of recombinant HBV vaccine at weeks 0, 4, and 24 (IM20 × 3 group, n = 145); 4 intramuscular double doses (40 μg [2 injections of 20 μg]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (IM40 × 4 group, n = 148); or 4 intradermal injections of low doses (4 μg [1/5 of 20 μg]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (ID4 × 4 group, n = 144). Percentage of responders at week 28, defined as patients with hepatitis B surface antibody (anti-HBs) of at least 10 mIU/mL in patients who received at least 1 dose of vaccine. Patients with missing anti-HBs titer measurement at the final follow-up visit at week 28 were considered as nonresponders in the primary (efficacy) analysis. A total of 437 patients were randomized to the 3 study groups, of whom 11 did not receive any vaccine. Of these, 396 had available anti-HBs titers at week 28. The percentage of responders at week 28 was 65% (95% confidence interval [CI], 56%-72%) in the IM20 × 3 group (n = 91), 82% (95% CI, 77%-88%) in the IM40 × 4 group (n = 119) (P < .001 vs IM20 × 3 group), and 77% (95% CI, 69%-84%) in the ID4 × 4 group (n = 108) (P = .02 vs IM20 × 3 group). No safety
Full Text Available The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector. CEA was expressed either in a membrane-bound form (wild-type CEA or in two truncated forms (CEA6 and CEA66 with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.
Zhang, Lu; Wang, Wei; Wang, Shixia
Summary The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: (1) features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant, and dosing; (2) individual variations among vaccine recipients; and (3) vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route, and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines. PMID:26313239
Visser, N; Egger, W; Lütticken, D
Initially the use of intradermal application of Aujeszky's disease vaccines was shown to be very effective. However, for thus far unknown reasons the gI-deleted vaccines were much less efficacious by using this route of vaccination as compared to gI-positive vaccines. By the use of a tocopherol-based adjuvant and an improved design of the intradermal injection device it now appeared feasible to obtain the same efficacy both in specific pathogen free pigs and in pigs with material antibodies as found before when intramuscular administration was performed. With respect to safety we found a complete lack of skin lesions, no adverse systemic reactions (e.g. body temperatures) and no effect on growth rates. Last but not least, the easiness of intradermal injections is of great advantage in large-scale vaccination programs.
Buchmann, Kurt; Desmukh, Sidhartha; Chettri, Jiwan Kumar
We have previously shown that immersion vaccination (30 sec) using the Aquavac Relera vaccine (containing formalin killed Yersinia ruckeri serotype O1 of both biotypes 1 and 2) provides the best protection (when compared to other commercial ERM vaccines on the Danish market) against infection...... following i. p. challenge using Y. ruckeri O1, biotype 2, which at present is the main bacterial pathogen in fingerling trout production in Denmark. Despite a significant protection conferred by this vaccine (immersion) some mortality could be observed following challenge. We have therefore performed...... a study in order to elucidate if different vaccine administration methods (using Aquavac Relera) can improve protection and reduce mortality of exposed trout following challenge with this particular pathogen. Rainbow trout (mean weight 7.8 g) reared at the Bornholm Salmon Hatchery under pathogen free...
Andrianov, Alexander K; DeCollibus, Daniel P; Gillis, Helice A; Kha, Henry H; Marin, Alexander; Prausnitz, Mark R; Babiuk, Lorne A; Townsend, Hugh; Mutwiri, George
Intradermal immunization using microfabricated needles represents a potentially powerful technology, which can enhance immune responses and provide antigen sparing. Solid vaccine formulations, which can be coated onto microneedle patches suitable for simple administration, can also potentially offer improved shelf-life. However the approach is not fully compatible with many vaccine adjuvants including alum, the most common adjuvant used in the vaccine market globally. Here, we introduce a polyphosphazene immuno adjuvant as a biologically potent and synergistic constituent of microneedle-based intradermal immunization technology. Poly[di(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine adjuvant and as a key microfabrication material. When used as part of an intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates superior activity in pigs compared to intramascular administration and significant antigen sparing potential. It also accelerates the microneedle fabrication process and reduces its dependence on the use of surfactants. In this way, PCPP-coated microneedles may enable effective intradermal vaccination from an adjuvanted patch delivery system.
Immunotherapy in viral warts with intradermal Bacillus Calmette–Guerin vaccine versus intradermal tuberculin purified protein derivative: A double-blind, randomized controlled trial comparing effectiveness and safety in a tertiary care center in Eastern India
Conclusion: Both intradermal Bacillus Calmette–Guerin and tuberculin purified protein derivative hold promise in the treatment of viral warts. Bacillus Calmette–Guerin may be more effective, though it had more adverse events in our study.
Full Text Available Abstract Background Although magnesium ions (Mg2+ are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+. To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short, tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.
Barfoed, Annette Malene; Kirstensen, Birte; Dannemann-Jensen, Tove
by histology. For selected combinations, vaccination efficiency in terms of antibody response was studied. Gene gun vaccination on ear alone was as efficient as a multi-site (ear, thorax, inguinal area, tongue mucosa) gene gun approach, and more efficient than combined intramuscular (i.m.)/intradermal (i...
Henry, S P; Grillone, L R; Orr, J L; Bruner, R H; Kornbrust, D J
The systemic toxicity of two phosphorothioate oligonucleotides specific for herpes simplex viruses (ISIS 1082) and human papiloma virus (ISIS 2105) were evaluated following repeated intradermal injections of vehicle control, 0.33, 2.17, or 21.7 mg/kg daily to Sprague-Dawley rats (10/sex/group) for 14 days. Animals were sacrificed 1 day after the last dose, except for a portion of the ISIS 1082-treated animals (5/sex/group) which were maintained for an additional 14-day recovery period. The profile of alterations noted for both compounds was very similar. Other than local signs of irritation at the site of injection, there were no clinical signs of toxicity or treatment-related mortality, but there was a slight decrease in body weight gain for the 21.7 mg/kg dose groups. Alterations in hematology parameters included dose-dependent thrombocytopenia and anemia. Alterations in serum chemistry parameters were suggestive of mild alterations in hepatic metabolism, with increases in liver transaminases and bilirubin, along with decreases in albumin and cholesterol. Both spleen and liver weights were significantly elevated in a dose-dependent fashion. Histopathological alterations noted in liver, kidney, lung, injection site skin, and spleen were characterized as perivascular and interstitial infiltrates of macrophages and monocytes. Additional microscopic alterations in the spleen included mild lymphoid hyperplasia (seen in lymph nodes as well), and extramedullary hematopoiesis. Treatment-related cytopenias were likely related to mild, focal hypocellularity in the bone marrow. Alterations in ISIS 1082-treated animals were only partially reversed following the 14-day treatment-free period. In conclusion, repeated intradermal administration of ISIS 1082 and ISIS 2105 produced a similar spectrum of toxicities, with liver, kidney, spleen, and bone marrow being identified as target tissues.
Masters, Nina B; Wagner, Abram L; Carlson, Bradley F; Boulton, Matthew L
Timely administration of recommended vaccines requires children to have multiple vaccines co-administered in the first year of life. The objectives of this study were to estimate the proportion of timely vaccinations and the proportion of co-administered vaccines, and to assess the relationship between vaccine co-administration and vaccine timeliness in Kenyan children. Using the 2014 Kenyan Demographic and Health Survey (DHS), we calculated the proportion of children who received co-administered and timely vaccine doses. Co-administration was defined as doses administered on the same day with dates recorded on vaccination cards. Vaccines were considered timely if given within four days before to four weeks after the recommended interval for administration. 10,385 children aged 1-4 years in the Kenyan 2014 DHS dataset had vaccination cards which comprised the study sample. Analysis revealed wide a range for receipt of timely doses, from 90.2% for OPV0 to 56.0% for Measles. Co-administration of the 6-week dose was associated with 2.81 times higher odds of a timely Penta dose 1 (95% CI: 2.28, 3.46) and birth-dose co-administration was associated with a substantial increase in timely BCG vaccination: AOR 7.43 (95% CI: 6.31, 8.75). Though vaccine coverage in Kenya was high, timely vaccination was markedly low, with resultant implications for population immunity and potential spread of communicable diseases in unvaccinated infants. Co-administration of vaccines, place of residence, wealth index, and child age were consistently related to the odds of timely vaccine receipt. These relationships reinforce the importance of dedicating resources to programs that educate low socio-economic groups about the importance of vaccine co-administration. Copyright © 2018 Elsevier Ltd. All rights reserved.
concerns associated with pWRG/VEE or delivery method identified during the Phase 1 study. 3.4. Tolerability of Vaccine Procedures To assess the...results of the Phase I clinical study of EP-mediated pWRG/VEE delivery demonstrate an acceptable safety and reactogenicity profile for the DNA vaccine...11] Hooper JW, Moon JE, Paolino KM, Newcomer R, McLain DE, Josleyn M, et al. A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment
Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia.
Clarke, Ed; Saidu, Yauba; Adetifa, Jane U; Adigweme, Ikechukwu; Hydara, Mariama Badjie; Bashorun, Adedapo O; Moneke-Anyanwoke, Ngozi; Umesi, Ama; Roberts, Elishia; Cham, Pa Modou; Okoye, Michael E; Brown, Kevin E; Niedrig, Matthias; Chowdhury, Panchali Roy; Clemens, Ralf; Bandyopadhyay, Ananda S; Mueller, Jenny; Jeffries, David J; Kampmann, Beate
The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7
Anand, Abhijeet; Zaman, K; Estívariz, Concepción F; Yunus, Mohammad; Gary, Howard E; Weldon, William C; Bari, Tajul I; Steven Oberste, M; Wassilak, Steven G; Luby, Stephen P; Heffelfinger, James D; Pallansch, Mark A
Inactivated poliovirus vaccine (IPV) introduction and phased oral poliovirus vaccine (OPV) cessation are essential for eradication of polio. Healthy 6-week old infants in Bangladesh were randomized to one of five study arms: receipt of trivalent OPV (tOPV) or bivalent OPV (bOPV) at ages 6, 10 and 14 weeks, intramuscular IPV or intradermal one-fifth fractional dose IPV (f-IPV) at ages 6 and 14 weeks, or f-IPV at ages 6 and 14 weeks with bOPV at age 10 weeks (f-IPV/bOPV). All participants received tOPV at age 18 weeks. Of 975 infants randomized, 95% (922) completed follow-up. Type 1 seroconversion after 3 doses at 6, 10 and 14 weeks was higher with bOPV compared with tOPV (99% vs 94%, p=0.019). Seroconversions to types 1 and 3 after 2 IPV doses at ages 6 and 14 weeks were no different than after 3 doses of tOPV or bOPV at ages 6, 10 and 14 weeks. A priming response, seroconversion 1 week after IPV at 14 weeks among those who did not seroconvert after IPV at 6 weeks, was observed against poliovirus types 1, 2 and 3 in 91%, 84% and 97%, respectively. Compared with IPV, f-IPV failed non-inferiority tests for seroconversion with 1 or 2 doses and priming after 1 dose. The findings demonstrate considerable priming with IPV at age 6 weeks, comparable immunogenicity of tOPV and bOPV, and inferior immunogenicity of one-fifth f-IPV compared with IPV. If IPV induced priming at age 6 weeks is similar to that at age 14 weeks, IPV could be administered at a younger age and possibly with a higher coverage. Published by Elsevier Ltd.
Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial.
Hung, Ivan Fan-Ngai; Zhang, Anna Jinxia; To, Kelvin Kai-Wang; Chan, Jasper Fuk-Woo; Li, Patrick; Wong, Tin-Lun; Zhang, Ricky; Chan, Tuen-Ching; Chan, Brian Chun-Yuan; Wai, Harrison Ho; Chan, Lok-Wun; Fong, Hugo Pak-Yiu; Hui, Raymond Kar-Ching; Kong, Ka-Lun; Leung, Arthur Chun-Fung; Ngan, Abe Ho-Ting; Tsang, Louise Wing-Ki; Yeung, Alex Pat-Chung; Yiu, Geo Chi-Ngo; Yung, Wing; Lau, Johnson Y-N; Chen, Honglin; Chan, Kwok-Hung; Yuen, Kwok-Yung
Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to clarify its effect in a younger age group. In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18-30 years in early 2014 to receive the 2013-14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID). Randomisation was by computer-generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus [A/California/H1N1], A/Victoria/361/2011 H3N2-like virus [A/Victoria/H3N2], and B/Massachusetts/2/2012-like virus [B/Yamagata lineage]) and four non-vaccine strains (A/HK/485197/14 [H3N2 Switzerland-like lineage], prototype A/WSN/1933 [H1N1], A/HK/408027/09 [prepandemic seasonal H1N1], and B/HK/418078/11 [Victoria lineage]). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02103023. We enrolled 160 healthy volunteers between March 1 and May 31, 2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain
Brouillette, M.; Doré, M.; Hébert, C.; Spooner, M.-F.; Marchand, S.; Côté, J.; Gobeil, F.; Rivest, M.; Lafrance, M.; Talbot, B. G.; Moutquin, J.-M.
We present a novel intradermal needle-free drug delivery device which exploits the unsteady high-speed flow produced by a miniature shock tube to entrain drug or vaccine particles onto a skin target. A first clinical study of pain and physiological response of human subjects study is presented, comparing the new injector to intramuscular needle injection. This clinical study, performed according to established pain assessment protocols, demonstrated that every single subject felt noticeably less pain with the needle-free injector than with the needle injection. Regarding local tolerance and skin reaction, bleeding was observed on all volunteers after needle injection, but on none of the subjects following powder injection. An assessment of the pharmacodynamics, via blood pressure, of pure captopril powder using the new device on spontaneously hypertensive rats was also performed. It was found that every animal tested with the needle-free injector exhibited the expected pharmacodynamic response following captopril injection. Finally, the new injector was used to study the delivery of an inactivated influenza vaccine in mice. The needle-free device induced serum antibody response to the influenza vaccine that was comparable to that of subcutaneous needle injection, but without requiring the use of an adjuvant. Although no effort was made to optimize the formulation or the injection parameters in the present study, the novel injector demonstrates great promise for the rapid, safe and painless intradermal delivery of systemic drugs and vaccines.
Altman, K D; Kelman, M; Ward, M P
Canine parvovirus (CPV) is a highly contagious and worldwide cause of serious and often fatal disease in dogs, despite the widespread availability of vaccines. Which vaccine-related factors are associated with vaccination failure is largely unknown, and there are no reports from Australia. In this study - the first national population-level CPV study of its kind ever conducted - we analysed data on 594 cases of apparent CPV vaccination failure reported from an Australian national surveillance system to determine whether vaccine strain, type or administration protocol are risk factors for vaccination failures. The strain of CPV used in vaccine manufacture was not significantly associated with vaccination failure in clinical practice. The vaccine type (killed versus attenuated vaccine) for puppies diagnosed with CPV was associated with a lower mean age at time of vaccination (P=0.0495). The age at administration of the last CPV vaccination a puppy received prior to presenting with disease was a significant (P=0.0334) risk factor for vaccination failure, irrespective of whether the vaccine was marketed for a 10-week or 12-week or greater vaccination finish protocol. There was also a strong negative correlation between age at last vaccination prior to disease and vaccination failure (Pfailure. This supports the hypothesis that the use of final vaccination in puppies at less than 16 weeks of age predisposes to vaccination failure and warrants a final age for vaccination recommendation to be at least 16 weeks for all canine parvovirus vaccines, especially in outbreak situations. The large number of cases identified in this study confirms that CPV vaccination failure is occurring in Australia. Veterinarians should consider CPV as a differential diagnosis in cases with appropriate clinical presentation, regardless of the reported vaccination status of the dog. Copyright © 2017 Elsevier B.V. All rights reserved.
Denis, François; Alain, Sophie; Ploy, Marie-Cécile
A successful vaccine triggers the interaction of various cells of the immune system as does a regular immune response. It is thus necessary to introduce the vaccine antigens into an anatomic site where they will contact immune cells. The route of administration is thus critical for the outcome of vaccination. Intramuscular or subcutaneous injections are the most popular. Antigens injected intramuscularly can form persistent precipitates that are dissolved and re-absorbed relatively slowly. If injecting antigens is a quick, easy and reproducible way to vaccination, it requires trained personnel. Alternatives exist, through non-invasive formulations which allow administration by the patient or a third party with no particular expertise. The skin, especially its epidermal layer, is an accessible and competent immune environment and an attractive target for vaccine delivery, through transcutaneous delivery or immunostimulant patches. Mucosal immunization is another strategy: its major rationale is that organisms invade the body via mucosal surfaces. Therefore, local protection at mucosal surface as well as systemic defense is beneficial. Various formulations of mucosal vaccines have been developed, such as the Sabin oral polio vaccine (OPV), rotavirus vaccines, cold-adapted influenza vaccines or vaccine against typhoid fever. Thus we are entering in an era where mucosal and transcutaneous immunisation will play an important role in disease management. However, it has not been so easy to obtain regulatory approval for mucosal or transcutaneous formulations and needle-based vaccines continue to dominate the market.
Intradermal adapter device technology minimizes the complexity of the Mantoux technique, thereby providing predictable, reproducible intradermal (ID) injections and removing the concerns regarding the ease and reliability of Mantoux technique when using conventional needle and syringe. The technology employs a simple device with geometry designed to gently deform the skin surface and the subcutaneous tissue, providing the ideal angle and depth of needle insertion for consistently successful intradermal injections. The results of this development were presented at the First, Second and Third Skin Vaccination Summits in 2011, 2013 and 2015 respectively [1,2,3]. The current publication addresses the performance of intradermal adapters (IDA) evaluated in three preclinical studies. The evaluations were based on the assessment of bleb formation in a skin model, an accepted indicator of ID injection success. All evaluated devices share the same proprietary dermal interface technology. Devices instituting this design are easy to use, require minimal training, and employ conventionally molded parts and cannula. These studies evaluated IDAs of initial design integral with luer lock needles, IDAs for use with conventional syringes, and intradermal adapters for use with auto disable syringes (ADID adapters). The evaluated ID adapters were intended to consistently place the lancet of the needle at a depth of 0.75mm from the skin's surface. This placement depth addresses the variation in the skin thickness at immunization sites for the majority of patients independent of many other variables. Most participants preferred the intradermal adapter method over the traditional Mantoux and identified a need for the adapter at their workplace. Evaluation of IDAs by registered nurses indicated these devices increase success of bleb formation. The use of IDA increased the success of forming blebs by about 30%. Nurses felt the injections were much easier to perform, in particular by
Wilson, Kumanan; Hawken, Steven; Kwong, Jeffrey C; Deeks, Shelley L; Crowcroft, Natasha S; Manuel, Douglas
Vaccine safety surveillance is a critical component of any population-wide vaccination program. In the province of Ontario, Canada we developed a vaccine safety surveillance system utilizing linked health administration databases. VISION (Vaccine and Immunization Surveillance in Ontario) has conducted population based self-controlled case series analyses to evaluate the safety of recommended pediatric vaccines in the general population and in specific subgroups. We present our experiences with developing this system including preliminary findings and challenges. Key methodological observations include: (1) aggregate health services data as an endpoint appears useful (2) graphical description of events following vaccination are valuable and (3) relative incidence ratios are helpful for overcoming the healthy vaccinee effect. Copyright © 2012 Elsevier Ltd. All rights reserved.
Zhao, Zhen; Smith, Philip J; Hill, Holly A
Routine administration of all age-appropriate doses of vaccines during the same visit is recommended for children by the National Vaccine Advisory Committee (NVAC) and the Advisory Committee on Immunization Practices (ACIP). Evaluate the potentially achievable vaccination coverage for ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (4+DTaP), ≥4 doses of pneumococcal conjugate vaccine (4+PCV), and the full series of Haemophilus influenzae type b vaccine (Hib-FS) with simultaneous administration of all recommended childhood vaccines. Compare the potentially achievable vaccination coverage to the reported vaccination coverage for calendar years 2001 through 2013; by state in the United States and by selected socio-demographic factors in 2013. The potentially achievable vaccination coverage was defined as the coverage possible for the recommended 4+DTaP, 4+PCV, and Hib-FS if missed opportunities for simultaneous administration of all age-appropriate doses of vaccines for children had been eliminated. Compared to the reported vaccination coverage, the potentially achievable vaccination coverage for 4+DTaP, 4+PCV, and Hib-FS could have increased significantly (Pvaccination coverage would have achieved the 90% target of Healthy People 2020 for the three vaccines beginning in 2005, 2008, and 2011 respectively. In 2013, the potentially achievable vaccination coverage increased significantly across all selected socio-demographic factors, potentially achievable vaccination coverage would have reached the 90% target for more than 51% of the states in the United States. The findings in this study suggest that fully utilization of all opportunities for simultaneous administration of all age-eligible childhood doses of vaccines during the same vaccination visit is a critical strategy for achieving the vaccination coverage target of Healthy People 2020. Encouraging providers to deliver all recommended vaccines that are due at each visit by
This podcast discusses seven simple ways to avoid vaccine administration errors in health care settings. Created: 2/16/2012 by National Center for Immunization and Respiratory Diseases (NCIRD). Date Released: 2/16/2012.
Lin, Jui-Chu; Wang, Triumph
Immunization is recognized as a powerful public health tool in disease control and eradication. Registered nurses (RNs) are the principal health professionals responsible for administering vaccines, not only in terms of childhood immunization but also increasingly in administering travel vaccines and annual influenza vaccinations. The RN often provides leadership in developing and maintaining a high quality program. The legal position of nurses when administering a vaccine conflicts with their role as care providers, and nurses must be aware of their legal position when administering a vaccine that has not been individually prescribed by a doctor. A recent case involving a baby who died after receiving a vaccine administered by a public health nurse without a doctor's prescription resulted in the prosecutor initiating a prosecution against the nurse and chief of Health Bureau for a violation of Article 28 of the Physician's Act and the criminal law. Although the nurse and Bureau Chief were judged not guilty, the first trial court pointed out that the behavior of this nurse still violated Article 28. This reflects the conflict that exists between empirical practice and legal regulations. In order to guarantee that prophylactic inoculation is implemented properly under legitimate and effective conditions (specially in remote districts), in May 23, 2006, Legislative Yuan passed an amendment to Article 4 of the Communicable Disease Control Act, which specified that no public health nurse can be prosecuted for violations of Article 28 of the Physician's Act as a result of vaccine administration. In the future, nurses in clinics located in remote districts may conduct prophylactic inoculation work without fear of the terms of Article 28 and focus on implementing public prophylactic inoculation responsibilities. However, a public health nurse can still be liable for the malpractice in criminal law during the vaccination. Therefore, following procedure is still necessary
Hultström, Michael; Roxhed, Niclas
The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines. PMID:24876605
Borggren, Marie; Nielsen, Jens; Karlsson, Ingrid
BACKGROUND: Pigs are natural hosts for influenza A viruses, and the infection is widely prevalent in swine herds throughout the world. Current commercial influenza vaccines for pigs induce a narrow immune response and are not very effective against antigenically diverse viruses. To control...... influenza in pigs, the development of more effective swine influenza vaccines inducing broader cross-protective immune responses is needed. Previously, we have shown that a polyvalent influenza DNA vaccine using vectors containing antibiotic resistance genes induced a broadly protective immune response...... of the optimized DNA vaccine were evaluated in groups of five to six pigs. The DNA vaccine consisted of six selected influenza genes of pandemic origin, including internally expressed matrix and nucleoprotein and externally expressed hemagglutinin and neuraminidase. RESULTS: Needle-free vaccination of growing pigs...
Bose, Anuradha; Munshi, Renuka; Tripathy, Radha Madhab; Madhusudana, Shampur N; Harish, B R; Thaker, Saket; Mahendra, B J; Gunale, Bhagwat; Gogtay, Nithya J; Thatte, Urmila M; Mani, Reeta Subramaniam; Manjunath, K; George, Kuryan; Yajaman, Ashwin Belludi; Sahai, Ashish; Dhere, Rajeev M; Alex, Reginald G; Adhikari, Debasis Das; Abhilash; Raghava, Venkata; Kumbhar, Dipti; Behera, Tapas Ranjan; Kulkarni, Prasad S
Rabies is a 100% fatal disease but preventable with vaccines and immunoglobulins. We have developed a new purified vero cell rabies vaccine (Rabivax-S) and evaluated its safety and immunogenicity in post-exposure prophylaxis by intramuscular (IM) and intradermal (ID) routes. This was a randomized active-controlled non-inferiority study in 180 individuals (age 5years and above) with suspected rabies exposure (90 each with WHO Category II and Category III exposures). The participants received either Rabivax-S (1mL IM; five doses), Rabivax-S (0.1mL ID; eight doses) or purified chick embryo cell vaccine (PCEC, Rabipur®) (1mL IM; five doses). The IM doses were given on Day 0, 3, 7, 14 and 28 while the ID doses were given on days 0, 3, 7 and 28. Category III patients also received a human rabies immunoglobulin (HRIG) on Day 0. Adverse events (AEs) were recorded with diary cards till day 42. Rabies neutralizing antibody levels were measured on day 0, 7, 14, 28 and 42. In both the category II and III patients, the geometric mean concentration (GMC) ratios of Rabivax-S IM and Rabivax-S ID groups to PCEC IM were more than 1, thus proving the non-inferiority. GMCs were similar or higher in Rabivax-S groups at all the time points. Seroresponse against rabies (RFFIT titre⩾0.5IU/mL) was achieved in all participants. Mostly mild local and systemic adverse events were reported across the three groups and all resolved without sequelae. Rabivax-S was well tolerated and showed immunogenicity comparable to a licensed rabies vaccine by both IM and ID routes in post-exposure prophylaxis. Registry No.: CTRI/2012/11/003135. Copyright © 2016 Elsevier Ltd. All rights reserved.
Borggren, Marie; Nielsen, Jens; Bragstad, Karoline
to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages...... expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations...
Babs E Verstrepen
Full Text Available The mosquito-borne West Nile virus (WNV causes human and animal disease with outbreaks in several parts of the world including North America, the Mediterranean countries, Central and East Europe, the Middle East, and Africa. Particularly in elderly people and individuals with an impaired immune system, infection with WNV can progress into a serious neuroinvasive disease. Currently, no treatment or vaccine is available to protect humans against infection or disease. The goal of this study was to develop a WNV-vaccine that is safe to use in these high-risk human target populations. We performed a vaccine efficacy study in non-human primates using the contemporary, pathogenic European WNV genotype 1a challenge strain, WNV-Ita09. Two vaccine strategies were evaluated in rhesus macaques (Macaca mulatta using recombinant soluble WNV envelope (E ectodomain adjuvanted with Matrix-M, either with or without DNA priming. The DNA priming immunization was performed with WNV-DermaVir nanoparticles. Both vaccination strategies successfully induced humoral and cellular immune responses that completely protected the macaques against the development of viremia. In addition, the vaccine was well tolerated by all animals. Overall, The WNV E protein adjuvanted with Matrix-M is a promising vaccine candidate for a non-infectious WNV vaccine for use in humans, including at-risk populations.
Bogacheva, N V; Darmov, I V; Borisevich, I V; Kriuchkov, A V; Pechenkin, D V
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.
Logomasini, Mark A; Stout, Richard R; Marcinkoski, Ron
Jet injection involves the use of a needle-free device that delivers a prescribed drug, vaccine, or compound intradermally, subcutaneously, or intramuscularly via high pressure produced by either a carbon-dioxide-filled or nitrogen-filled cartridge or a spring. During that procedure, the injector is held at an angle against the patient's skin, and a very fine stream of liquid medication is forced through a tiny orifice in the device, penetrates the skin in a selected volume ranging from 0.05 mL to 1.0 mL, and is deposited in the underlying tissue. When compared with methods of injection that require a needle, jet injection offers multiple benefits. It can be less painful for the patient, and it enhances compliance, reduces risks such as needlestick injuries and cross-contamination, eliminates the need for "sharps" disposal, and enables (with minimal training) the reliable, reproducible, and accurate delivery of medication. Patient convenience is also a factor: Jet injectors are designed for self-medication as well as professional use. It must be remembered, however, that treatment via jet injection is not always painless. Because of their formulations, some medications and vaccines produce a burning or stinging sensation, whether they are administered with a jet injector or a needle. Some compounded preparations, like the formulations included in this article, can be administered by jet injection, a practice that we suggest will increase in popularity as more drugs are prescribed for administration in the home setting. Because changes in drug concentration may be required to effect the transfer of an agent or ensure the accurate reconstitution of a lyophilized drug administered with a jet injector, the skill of a compounding pharmacist will be essential in preparing customized injectates. In this article, we address the use of needle-free technology in general; present examples of carbon-dioxide, spring-powered, and novel jet injection systems; and answer questions
Bagg, Andrew; Chacko, Thomas; Lockey, Richard
Allergy skin testing is a common procedure for the diagnosis of atopic diseases with a small risk of systemic reactions. To determine the 12-month incidence of systemic reactions (SRs) to skin prick testing (SPT) and intradermal skin testing (ST) and the symptoms and response to immediate treatment with epinephrine intramuscularly. A prospective study was conducted to evaluate SRs from ST in 1,456 patients. A standard form was used to record symptoms, signs, and treatment. The SRs are defined as any sign or symptom other than a local reaction thought to be secondary to ST. No vasovagal reactions were included. Nurses, as instructed by attending physicians, administered epinephrine (0.2 mL of a 1:1,000 dilution) intramuscularly in the deltoid as soon as any remote signs or symptoms occurred. Fifty-two patients (3.6%) had SRs (6 SPT and 46 intradermal): 43 (83%) were female, and 17 (33%) had asthma. Systemic symptoms included (SPT/intradermal) pruritic eyes, nose, or pharynx (0%/46%); worsening cough (50%/26%); sensation of difficulty swallowing (0%/20%); worsening nasal congestion (17%/15%); rhinorrhea (17%/13%); chest tightness or shortness of breath (33%/11%); generalized pruritus (17%/11%); sneezing (33%/9%); wheeze (0%/4%); and urticaria (17%/2%). No severe asthma, shock, hypotension, unconsciousness, or biphasic reactions occurred. All 52 patients received epinephrine intramuscularly, 48 (92%) oral prednisone, 9 (17%) oral prednisone to take 6 to 8 hours after a reaction, 50 (96%) oral antihistamine, and 6 (12%) nebulized beta-agonist. Of patients who underwent ST, SRs occurred in 3.6% (0.4% for SPT and 3.2% for intradermal ST), all of whom readily responded to epinephrine intramuscularly in the deltoid. This immediate administration of epinephrine seems to prevent more serious and biphasic reactions.
Wyman, Marcia J; Stabi, Katie L
To determine whether concomitant administration of zoster vaccine and polysaccharide pneumococcal-23 vaccine (PPV23) provides sufficient protection against herpes zoster infections. Literature was retrieved through the Centers for Disease Control and Prevention (CDC) website, PubMed (inception-February 2013), and Scopus (inception-February 2013) using the key words herpes zoster, pneumococcal, vaccine, concomitant, simultaneous administration, Pneumovax, Zostavax, and barriers. In addition, reference citations from publications were used. All English-language articles identified from the data sources were evaluated. Two studies evaluating concomitant and nonconcomitant administration of zoster vaccine and PPV23 were included. Current product labeling recommends a 4-week interval between zoster vaccine and PPV23 administration; however, the Food and Drug Administration (FDA) and the CDC promote concomitant administration to prevent a missed opportunity to vaccinate. This has caused confusion among health care professionals regarding the appropriate timing of these vaccines. A randomized trial that evaluated the immunogenicity of zoster vaccine and PPV23 given together versus separated by at least 4 weeks demonstrated that the varicella zoster virus (VZV) antibody levels of concomitant versus nonconcomitant vaccination groups did not meet noninferiority requirements. However, a large retrospective cohort trial that compared the incidence of herpes zoster infections following concomitant versus nonconcomitant administration of PPV23 and zoster vaccine did not find a statistically significant between-group difference. Concomitant administration of zoster vaccine and PPV23 is advocated by the CDC and FDA to improve immunization rates among vaccine-eligible individuals. Since there is no direct evidence that simultaneous administration of zoster vaccine and PPV23 puts patients at increased risk of developing herpes zoster, the vaccines should be given during the same
Lechiche, C; Charpille, M; Saissi, G; Sotto, A
Tuberculosis is a major public health problem. In France, the vaccine against tuberculosis (Bacillus Calmette-Guerin, BCG) is in decline. This decline is firstly due to changes in BGG administration that were implemented in 2006 and secondly because of new recommandations in 2007 that ended compulsory vaccination. To determine their position on this vaccine, in 2013-2014 we asked general practitioners, pediatricians, and Maternal and Infantile Protection Center physicians in the Gard and Herault departments (in Southern France) why this vaccine was not administered and their suggestions for improvement. Most of these doctors (73.9%) stated that they did not oppose this vaccination for children. They expressed concern about potential side effects, technical problems (intradermic injection, multi-dose bottles) and parents' refusal. One quarter of these physicians would have preferred that this vaccine remains compulsory and one third that this vaccine be administered in the maternity hospital. They also requested simplified criteria for patient eligibility, technical improvements (training for intradermal injection, single-dose vaccine) and more information for the public concerning this vaccination. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun
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
Bakhache, P; Rodrigo, C; Davie, S; Ahuja, A; Sudovar, B; Crudup, T; Rose, M
The New Vaccinations of Infants in Practice online survey in seven countries evaluated vaccination-related attitudes and concerns of parents of infants and health care providers (HCPs) who provide pediatric medical care. The survey showed that HCPs and parents were open to adding new vaccines to the immunization schedule, even if it requires co-administration with current vaccines or introduction of new office visits. Parental disease awareness campaigns would be helpful to achieve widespread acceptance of changes to vaccination schedules. In addition, HCPs would ideally provide disease education to parents to accompany recommendations for a new vaccine.
Background Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination proportional to the population at each point in time. Methods We present a SIR-like model that explicitly takes into account vaccine supply and the number of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the non-proportional model of vaccination and compare it to the proportional scheme typically found in the literature. Results The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity. Conclusions The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing
Budimir, Natalija; de Haan, Aalzen; Meijerhof, Tjarko; Gostick, Emma; Price, David A; Huckriede, Anke; Wilschut, Jan
Development of influenza vaccines capable of inducing broad protection against different virus subtypes is necessary given the ever-changing viral genetic landscape. Previously, we showed that vaccination with whole inactivated virus (WIV) induces heterosubtypic protection against lethal virus infection in mice. Whole inactivated virus-induced cross-protection was found to be mediated primarily by flu-specific CD8+ T cells. As it has been demonstrated that the route of vaccine administration strongly influences both the quantity and quality of vaccine-induced immunity, in this study, we determined which route of WIV administration induces optimal heterosubtypic cross-protection. We compared the magnitude of the immune response and heterosubtypic protection against lethal A/PR/8/34 (H1N1) infection after subcutaneous (SC), intramuscular (IM), and intranasal (IN) vaccination with A/NIBRG-14 (H5N1) WIV. Subcutaneous and IM administration was superior to IN administration of influenza WIV in terms of flu-specific CD8+ T-cell induction and protection of mice against lethal heterosubtypic challenge. Surprisingly, despite the very low flu-specific CD8+ T-cell responses detected in IN-vaccinated mice, these animals were partially protected, most likely due to cross-reactive IgA antibodies. The results of this study show that the magnitude of WIV-induced flu-specific CD8+ T-cell activity depends on the applied vaccination route. We conclude that parenteral administration of WIV vaccine, in particular IM injection, is superior to IN vaccine delivery for the induction of heterosubtypic cross-protection and generally appears to elicit stronger immune responses than mucosal vaccination with WIV. © 2013 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.
Lafeber AF; Klis FRM van der; Marzec AHJO; Labadie J; Ommen R van; Strieder TG; Berbers GAM; Utrecht Stichting Thuiszorg; Amersfoort Stichting Thuiszorg Eemland (STE),; LVO
In this study we compared the recommended subcutaneous administration of the RIVM MMR vaccine with the intramuscular administration for both safety and immunogenicity. Study subjects were 14 months old children, living in Amersfoort or Utrecht, who were eligible for their first MMR vaccination.
Esposito, Susanna; Mastrolia, Maria Vincenza; Prada, Elisabetta; Pietrasanta, Carlo; Principi, Nicola
Pediatric patients with severe chronic kidney disease (CKD) on conservative treatment, on dialysis, and those with renal transplantation are at a higher risk for infectious diseases as the result of impaired immune responses against infectious agents. Infections in these patients can have drastic consequences for disease morbidity and mortality. Immunization is a crucial preventive strategy for disease management in this pediatric population. However, vaccination coverage among children with CKD remains low due to safety concerns and doubts about vaccine immunogenicity and efficacy. In this study, we reviewed why children with CKD are at higher risk of infections, the importance of vaccinations among these children, barriers to vaccinations, and recommend the best vaccination schedules. Overall, vaccines have acceptable immunogenicity, efficacy, and safety profiles in children with CKD. However, in some cases, the protective antibody levels induced by vaccines and the benefits and risks of booster vaccine doses must be individually managed. Furthermore, close contacts and household members of these children should complete age-appropriate vaccination schedules to increase the child's indirect protection.
Kraan, H.; Stel, van der W.; Kersten, G.F.A.; Amorij, J.P.
Global polio eradication is closer than ever. Replacement of the live attenuated oral poliovirus vaccine (OPV) by inactivated poliovirus vaccine (IPV) is recommended to achieve complete eradication. Limited global production capacity and relatively high IPV costs compared to OPV spur the need for
Nothaft, H; Perez-Muñoz, M E; Gouveia, G J; Duar, R M; Wanford, J J; Lango-Scholey, L; Panagos, C G; Srithayakumar, V; Plastow, G S; Coros, C; Bayliss, C D; Edison, A S; Walter, J; Szymanski, C M
Source attribution studies report that consumption of contaminated poultry is the primary source for acquiring human campylobacteriosis. Oral administration of an engineered Escherichia coli strain expressing the Campylobacter jejuni N-glycan reduces bacterial colonization in specific-pathogen-free leghorn chickens, but only a fraction of birds respond to vaccination. Optimizing the vaccine for commercial broiler chickens has great potential to prevent pathogen entry into the food chain. Here, we tested the same vaccination approach in broilers and observed similar efficacy in pathogen load reduction, stimulation of host IgY response, lack of C. jejuni resistance development, uniformity in microbial gut composition, and bimodal response to treatment. Gut microbiota analysis of leghorn and broiler vaccine responders identified one member of the Clostridiales XIVa cluster, Anaerosporobacter mobilis, significantly more abundant in responder birds. In broilers, co-administration of the live vaccine with A. mobilis or Lactobacillus reuteri, a commonly used probiotic, resulted in increased vaccine efficacy, antibody response, and weight gain. To investigate whether the responder/non-responder effect was due to selection of a C. jejuni 'super colonizer mutant' with altered phase-variable genes, we analysed all polyG-containing loci of the input strain compared to non-responder colony isolates and found no evidence of phase state selection. However, untargeted NMR-based metabolomics identified a potential biomarker negatively correlated with C. jejuni colonization levels possibly linked to the increased microbial diversity in this subgroup. The comprehensive methods used to examine the vaccine response bimodality provide several opportunities to improve the C. jejuni vaccine and the efficacy of any vaccination strategy.ImportanceCampylobacter jejuni is a common cause of human diarrheal disease worldwide and listed by the World Health Organization as a high priority
Preza, Iria; Subaiya, Saleena; Harris, Jennifer B; Ehlman, Daniel C; Wannemuehler, Kathleen; Wallace, Aaron S; Huseynov, Shahin; Hyde, Terri B; Nelaj, Erida; Bino, Silvia; Hampton, Lee M
Albania introduced inactivated polio vaccine (IPV) into its immunization system in May 2014, increasing the maximum recommended number of injectable vaccines given in a single visit from 2 to 3. Health-care providers and caregivers were interviewed at 42 health facilities in Albania to assess knowledge, attitudes, and practices regarding injectable vaccine administration. Immunization register data were abstracted from December 2014 to July 2015 at the same facilities to explore the number of injectable vaccines children received during their 2- and 4-month visits. The majority of children (87%) identified in the record review at either their 2- or 4-month immunization visit received all 3 injectable vaccines in a single visit. Almost all children who did not receive the vaccines in a single visit were subsequently fully immunized, most within a 2-week period. Over half of caregivers whose children got 3 or more injectable vaccines in a single visit reported being only comfortable with 1 or 2 injectable vaccines in a single visit. Despite most caregivers expressing hesitation regarding children receiving multiple injectable vaccines in a single visit, most children received vaccines according to the recommended schedule. Almost all children eventually received all recommended vaccines.
Dominique N Price
Full Text Available Bacille Calmette-Guérin (BCG is currently the only approved vaccine against tuberculosis (TB and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium, a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.
Jhaveri, Ravi; Allyne, Kristin
Intranasal vaccines are being developed for protection against many different infectious agents. The currently available intranasal live attenuated influenza vaccine (LAIV) is only approved for administration by medical personnel. We conducted a pilot study to investigate the feasibility of training parents to give LAIV to their own children. Subjects were recruited from several sources: a university-based outpatient clinic, university employee e-mail announcement, and direct referrals from study subjects. After confirming eligibility to receive LAIV, consented parents were trained by viewing a video with the study staff. LAIV was provided in a cooler with instructions to vaccinate within 24 hours. Telephone follow-up was conducted to confirm proper administration and to assess parental attitudes about home administration. At season's end, immunization registry and hospital records were reviewed to confirm no additional doses were given. Twenty-seven families with 41 children were enrolled. All participants successfully administered LAIV to their children, and all preferred or strongly preferred home administration to an office visit for getting vaccinated. Two families stated that without this option they would not have otherwise vaccinated their children. Adverse events were minor. All patients had their state vaccine registries accurately updated and none received duplicate doses. Upon review, no reimbursement was received for vaccination. Home administration of intranasal LAIV was successful and well received. This option could be used in the future for LAIV or other intranasal vaccines as a way to increase vaccination rates and convenience for parents. ClinicalTrials.gov identifier: NCT01938170. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau
Fisker, Ane Bærent; Ravn, Henrik Bylling; Rodrigues, Amabelia
Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine...... is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar...
Curran, T; McCaughey, C; Ellis, J; Mitchell, S J; Feeney, S A; Watt, A P; Mitchell, F; Fairley, D; Crawford, L; McKenna, J; Coyle, P V
False-positive PCR results usually occur as a consequence of specimen-to-specimen or amplicon-to-specimen contamination within the laboratory. Evidence of contamination at time of specimen collection linked to influenza vaccine administration in the same location as influenza sampling is described. Clinical, circumstantial and laboratory evidence was gathered for each of five cases of influenza-like illness (ILI) with unusual patterns of PCR reactivity for seasonal H1N1, H3N2, H1N1 (2009) and influenza B viruses. Two 2010 trivalent influenza vaccines and environmental swabs of a hospital influenza vaccination room were also tested for influenza RNA. Sequencing of influenza A matrix (M) gene amplicons from the five cases and vaccines was undertaken. Four 2009 general practitioner (GP) specimens were seasonal H1N1, H3N2 and influenza B PCR positive. One 2010 GP specimen was H1N1 (2009), H3N2 and influenza B positive. PCR of 2010 trivalent vaccines showed high loads of detectable influenza A and B RNA. Sequencing of the five specimens and vaccines showed greatest homology with the M gene sequence of Influenza A/Puerto Rico/8/1934 H1N1 virus (used in generation of influenza vaccine strains). Environmental swabs had detectable influenza A and B RNA. RNA detection studies demonstrated vaccine RNA still detectable for at least 66 days. Administration of influenza vaccines and clinical sampling in the same room resulted in the contamination with vaccine strains of surveillance swabs collected from patients with ILI. Vaccine contamination should therefore be considered, particularly where multiple influenza virus RNA PCR positive signals (e.g. H1N1, H3N2 and influenza B) are detected in the same specimen.
Simmons, Jonathan; Marston, Jeremy; Fisher, Paul; Broderick, Kate
Needle-free methods of drug delivery circumvent the drawbacks associated with the use of hypodermic needles such as needle-stick injuries, needle-phobia, cross contamination and disposal. Furthermore, pioneering DNA-based vaccines that aim to treat cancer and fight infectious diseases, such as HIV, Ebola and Zika, require precise deposition into the skin to target the immune response producing cells found only in the epidermis and dermis. Intradermal (ID) delivery can be achieved using a needle and the Mantoux technique but this requires a highly skilled technician and so extensive use of DNA vaccines calls for an alternative method of delivery. One option is jet injection which has been employed in mass vaccination programs for intramuscular or subcutaneous delivery and is used by some diabetic patients to inject insulin. In this talk I will present results from our ongoing ex-vivo experimental study into ID jet injection. Ultra-high-speed imaging is used to visualize the process of the jet exiting the nozzle and striking excised skin. A skin bleb grows as liquid is deposited within the skin. I will discuss how the control parameters, such as the rheological profile of the liquid and the stand-off distance, influence the volume of liquid successfully delivered intradermally.
Jones, Melissa; Cook, Robert
Objective and Participants: In 2006, the authors examined intention to receive an HPV vaccine among 340 college students. Methods: A total of 138 men and 202 women completed questionnaires. The authors measured intention by asking participants how likely they would be to accept an HPV vaccine that prevented against (1) all HPV, (2) cervical cancer…
A randomized clinical trial in adults and newborns in South Africa to compare the safety and immunogenicity of bacille Calmette-Guérin (BCG) vaccine administration via a disposable-syringe jet injector to conventional technique with needle and syringe.
Geldenhuys, Hennie D; Mearns, Helen; Foster, Jennifer; Saxon, Eugene; Kagina, Benjamin; Saganic, Laura; Jarrahian, Courtney; Tameris, Michele D; Dintwe, One B; Van Rooyen, Michele; Luabeya, Kany-Kany A; Hussey, Gregory; Scriba, Thomas J; Hatherill, Mark; Zehrung, Darin
Intradermal bacille Calmette-Guérin (BCG) vaccination by needle-free, disposable-syringe jet injectors (DSJI) is an alternative to the Mantoux method using needle and syringe (NS). We compared the safety and immunogenicity of BCG administration via the DSJI and NS techniques in adults and newborn infants at the South African Tuberculosis Vaccine Initiative (SATVI) research site in South Africa. Thirty adults and 66 newborn infants were randomized 1:1 to receive intradermal BCG vaccine (0.1 mL in adults; 0.05 mL in infants) via DSJI or NS. Wheal diameter (mm) and skin fluid deposition at the site of injection (SOI) were measured immediately post-vaccination. Adverse events and SOI reactogenicity data were collected 30 min and 1, 2, 4, and 12 weeks after vaccination for adults and at 30 min and 4, 10, and 14 weeks for infants. Blood was collected in infants at 10 and 14 weeks to assess BCG-specific T-cell immune responses. More infant BCG vaccinations by DSJI deposited >5 μL fluid on the skin surface, compared to NS (49% versus 9%, p=0.001). However, all 12 infant vaccinations that did not produce any SOI wheal occurred in the NS group (36%, pBCG scars after three months did not differ in adults (combined 97%, p=0.67) or infants (combined 62%, p=0.13). Frequencies of BCG-specific clusters of differentiation 4 (CD4) and clusters of differentiation 8 (CD8) T-cells co-expressing IFN-γ, TNF-α, IL-2, and/or IL-17 were not different in the DSJI and NS groups. BCG vaccination of newborn infants via DSJI was more likely to deliver an appropriate intradermal wheal at the SOI as compared to NS, despite leaving more fluid on the surface of the skin. Safety, reactogenicity, and antigen-specific T-cell immune responses did not differ between DSJI and NS techniques. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Waeckerle-Men, Ying; Bruffaerts, Nicolas; Liang, Yuan; Jurion, Fabienne; Sander, Peter; Kündig, Thomas M; Huygen, Kris; Johansen, Pål
Vaccination with Mycobacterium bovis BCG provides limited protection against pulmonary tuberculosis and a risk of dissemination in immune-compromised vaccinees. For the development of new TB vaccines that stimulate strong T-cell responses a variety of strategies is being followed, especially recombinant BCG and attenuated M. tuberculosis. The objective of the current study was to test potential benefits of vaccination through direct lymph-node targeting of wildtype BCG; the recommended route of vaccination with BCG is intradermal. C57BL/6 mice were immunised with BCG by intradermal, subcutaneous or intralymphatic injections. Cellular immune responses and protection against M. tuberculosis were determined. Intralymphatic vaccination was 100-1000 times more effective in stimulating BCG-specific immune responses than intradermal or subcutaneous immunisation. Intralymphatic administration stimulated high frequencies of mycobacterium-specific lymphocytes with strong proliferating capacity and production of TNF-α, IL-2, IL-17 and, especially, IFN-γ secretion by. CD4 and CD8 T cells. Most importantly, intralymphatic vaccination with 2×10(3)CFU BCG induced sustained protection against M. tuberculosis in intratracheally challenged C57BL/6 mice, whereas subcutaneous vaccination with 2×10(5)CFU BCG conferred only a transient protection. Hence, direct administration of M. bovis BCG to lymph nodes demonstrates that efficient targeting to lymph nodes may help to overcome the efficacy problems of vaccination with BCG. Copyright © 2013 Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background In 2001, two hexavalent vaccines were licensed in Italy (Hexavac®, Infanrix Hexa®, and since 2002 were extensively used for primary immunization in the first year of life (at 3, 5, 11/12 months of age. In 2005, the market authorization of Hexavac® was precautionary suspended by EMEA, because of doubts on long-term protection against hepatitis B virus. The objectives of this study were to evaluate the persistence of antibodies to anti-HBs, in children in the third year of life, and to investigate the response to a booster dose of hepatitis B vaccine. Methods Participant children were enrolled concomitantly with the offering of anti-polio booster dose, in the third year of life. Anti-HBs titers were determined on capillary blood samples. A booster dose of hepatitis B vaccine was administered to children with anti-HBs titers Results Sera from 113 children previously vaccinated with Hexavac®, and from 124 vaccinated with Infanrix Hexa® were tested for anti-HBs. Titers were ≥ 10 mIU/ml in 69% and 96% (p Post-booster, 93% of children achieved titers ≥ 10 mIU/ml, with no significant difference by vaccine group. Discussion Fifteen months after third dose administration, a significant difference in anti-HBs titers was noted in the two vaccine groups considered. Monovalent hepatitis B vaccine administration in 3-year old children induced a proper booster response, confirming that immunologic memory persists in children with anti-HBs titers
Safety Profile and Immunologic Responses of a Novel Vaccine Against Shigella sonnei Administered Intramuscularly, Intradermally and Intranasally: Results From Two Parallel Randomized Phase 1 Clinical Studies in Healthy Adult Volunteers in Europe
Interpretation: Intramuscularly administered Shigella sonnei GMMA vaccine is well tolerated, up to and including 5.9/100 μg and induces antibody to the OAg of at least the same magnitude of those observed following natural exposure to the pathogen. Vaccine administered by ID or IN, although well tolerated, is poorly immunogenic at the doses delivered. The data support the use of the GMMA technology for the development of intramuscular multivalent Shigella vaccines.
Luque, John S; Tarasenko, Yelena N; Dixon, Betty T; Vogel, Robert L; Tedders, Stuart H
This study explores the prevalence and provider- and practice-related correlates of physician recommendation and administration of the quadrivalent human papillomavirus (HPV) vaccine, Gardasil, to 11- to 12-year-old girls and the intention to recommend the HPV vaccine to 11- to 12-year-old boys in Georgia. The study also describes physician knowledge about and barriers to HPV vaccination. This cross-sectional study was conducted from December 2010 to February 2011. The study sample was drawn using the Georgia Vaccines for Children (VFC) provider list as a sampling frame and probability 1-stage cluster sampling with counties as clusters. The final analytic sample was restricted to 206 provider locations. Weighted percentages and corresponding statistics were calculated accounting for selection probabilities, nonresponse, and the cluster sample design. Among Georgia VFC providers attending to 11- to 12-year-old girls, 46% had always recommended that their patients get the HPV vaccination and 41% had vaccinated their female patients. Among Georgia VFC providers attending to 11- to 12-year-old boys, 20% would always recommend that their male patients get vaccinated.Physicians most frequently endorsed costs of stocking the vaccine (73%), upfront costs (69%), vaccination (68%), and insurance reimbursements (63%) as barriers to their HPV vaccination practices. Despite the Advisory Committee on Immunization Practices' recommendations on HPV vaccination, the prevalence of recommending and administering the HPV vaccine to female and male patients, aged 11 to 12 years, by VFC providers is an ongoing challenge in Georgia.
Schmeink, C.E.; Bekkers, R.L.M.; Josefsson, A.; Richardus, J.H.; Berndtsson Blom, K.; David, M.P.; Dobbelaere, K.; Descamps, D.
BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV
Kurtz, Sherry L; Bosio, Catharine M; De Pascalis, Roberto; Elkins, Karen L
Our laboratory has employed in vitro and in vivo mouse models based on Francisella tularensis Live Vaccine Strain (LVS)-induced protection to elucidate immune correlates for intracellular bacteria. Among the effectors found was GM-CSF, a pleiotropic cytokine that is integral to the development and proliferation of myeloid cells, including alveolar macrophages. GM-CSF has roles in resistance to primary murine infection with several intracellular pathogens, but its role during Francisella infection is unknown. Francisella is an intracellular pathogen that infects lungs after inhalation, primarily invading alveolar macrophages. Here we show that GM-CSF has route-dependent roles during primary infection of mice with LVS. GM-CSF deficient (GM-CSF KO) mice were slightly more susceptible than wild type to intradermal infection, but had increased resistance to intranasal infection. Similarly, these mice had increased resistance to pulmonary infection with virulent F. tularensis (SchuS4). LVS-vaccinated GM-CSF KO mice had normal adaptive immune responses, as measured by T cell activities after LVS intradermal or intranasal vaccination, and survived lethal secondary LVS challenge. GM-CSF KO mice also had robust humoral responses, producing elevated levels of serum antibodies following LVS vaccination compared to wild type mice. Taken together, our data demonstrates that the absence of GM-CSF improves resistance to pulmonary, but not intradermal, infection with Francisella. Published by Elsevier Masson SAS.
Al-Zahrani, Sharifa; Zaric, Marija; McCrudden, Cian; Scott, Chris; Kissenpfennig, Adrien; Donnelly, Ryan F
Breaching the skin's stratum corneum barrier raises the possibility of the administration of vaccines, gene vectors, antibodies and even nanoparticles, all of which have at least their initial effect on populations of skin cells. Intradermal vaccine delivery holds enormous potential for improved therapeutic outcomes for patients, particularly those in the developing world. Various vaccine-delivery strategies have been employed, which are discussed in this review. The importance of cutaneous immunobiology on the effect produced by microneedle-mediated intradermal vaccination is also discussed. Microneedle-mediated vaccines hold enormous potential for patient benefit. However, in order for microneedle vaccine strategies to fulfill their potential, the proportion of an immune response that is due to the local action of delivered vaccines on skin antigen-presenting cells, and what is due to a systemic effect from vaccines reaching the systemic circulation, must be determined. Moreover, industry will need to invest significantly in new equipment and instrumentation in order to mass-produce microneedle vaccines consistently. Finally, microneedles will need to demonstrate consistent dose delivery across patient groups and match this to reliable immune responses before they will replace tried-and-tested needle-and-syringe-based approaches.
Ravish, Hardanahalli S; Sudarshan, Mysore K; Madhusudana, Shampur N; Annadani, Rachana R; Narayana, Doddabele H Ashwath; Belludi, Ashwin Y; Anandaiah, Gangaboraiah; Vijayashankar, Veena
Rabies post exposure prophylaxis with cell culture vaccines by either intramuscular route or intradermal route spans over a period of one month. World Health Organization recommends completing post exposure prophylaxis against rabies with the same cell culture or embryonated egg rabies vaccine and with same route of administration and any deviation from this shall be an exception. In the present study, the safety and immunogenicity of rabies post-exposure prophylaxis was studied prospectively in 90 animal bite cases that had interchangeability of rabies vaccines either by route of administration or brand/type and such changes had occurred due to logistical/financial problems. Among them, 47 had change in route of administration from intramuscular to intradermal or vice versa and 43 had change in the brand/type of cell culture rabies vaccine. All of them had category III rabies exposure and received equine rabies immunoglobulin along with the rabies vaccine. None of the study subjects had any adverse reactions. The rabies virus neutralizing antibody titers was assessed by rapid fluorescent focus inhibition test and all the vaccinees had titers ≥0.5 IU per mL on day 14 which is considered as adequate for protection against rabies. Thus, the present study showed that, rabies post-exposure prophylaxis was safe and immunogenic despite changes in the route of administration and brand/type of rabies vaccine.
Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E
The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.
Badiu, Iuliana; Geuna, Massimo; Heffler, Enrico; Rolla, Giovanni
A 17-year-old girl reported generalised urticaria, eyelid angioedema, rhino-conjunctivitis, dyspnoea and wheezing 1 h after third intramuscular administration of quadrivalent human papilloma virus vaccine (Gardasil). She was treated with antihistamine, and corticosteroids with prompt relief of rhinitis and dyspnoea, while urticaria and angioedema lasted 24 h. Intradermal test with Gardasil, which contains polysorbate 80 (PS80), resulted positive, while skin tests with the bivalent vaccine were negative. Prick test performed with PS80 resulted positive in the patient and negative in ten healthy controls. The CD203 basophil activation test result was negative for PS80 at all the tested dilutions and specific IgE was not found. As flu vaccine was recommended, the authors skin tested two flu vaccine, one containing PS80 (Fluarix, GSK), which resulted positive and another flu vaccine with no adjuvant or preservative (Vaxigrip, Sanofi Pasteur MSD), which gave negative results. The patient then received Vaxigrip without adverse reactions.
Rotiroti, Giuseppina; Shamji, Mohamed; Durham, Stephen R; Till, Stephen J
Subcutaneous immunotherapy with high-dose grass pollen was first described more than 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. In contrast, low-dose subcutaneous immunotherapy has not shown clinical benefit. Uncontrolled reports from the early 20th century describe low-dose allergen inoculation directly into the dermis, an immunologically active area containing abundant dendritic cells and lymphatics. We sought to investigate the effect of low-dose intradermal grass pollen administration on cutaneous reactivity to allergen. Thirty adults sensitized to grass and tree pollens were randomized to receive (1) 6 repeat intradermal injections at 2-week intervals of grass pollen extract (estimated 7 ng of the major grass allergen Phl p 5 per injection), (2) 2 intradermal injections separated by 10 weeks, or (3) a single intradermal injection at 10 weeks. At the end of the study, cutaneous early and late responses were measured after double-blind intradermal injection with grass and birch pollen. Participants who received 6 fortnightly intradermal grass pollen injections had markedly smaller cutaneous late responses to grass pollen than control subjects who received 2 injections separated by 10 weeks (P pollen-specific IgG antibodies. Suppression was observed whether late responses were measured on the arms or the back. However, early responses were equivalent in all groups. Low-dose intradermal allergen, like conventional subcutaneous high-dose immmunotherapy, suppresses allergen-induced cutaneous late responses in a manner that is allergen specific, systemic, and associated with induction of IgG antibodies. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Voza, Tatiana; Kebaier, Chahnaz; Vanderberg, Jerome P
Intravenous injection of mice with attenuated Plasmodium berghei sporozoites induces sterile immunity to challenge with viable sporozoites. Non-intravenous routes have been reported to yield poor immunity. Because intravenous immunization has been considered to be unacceptable for large scale vaccination of humans, assessment was made of the results of intradermal immunization of mice with Plasmodium yoelii, a rodent malaria parasite whose infectivity resembles that of human malaria. Mice were immunized with two injections of isolated, radiation-attenuated P. yoelii sporozoites, either by intravenous (IV) or intradermal (ID) inoculation. In an attempt to enhance protective immunogenicity of ID-injections, one group of experimental mice received topical application of an adjuvant, Imiquimod, while another group had their injections accompanied by local "tape-stripping" of the skin, a procedure known to disrupt the stratum corneum and activate local immunocytes. Challenge of immunized and non-immunized control mice was by bite of sporozoite-infected mosquitoes. Degree of protection among the various groups of mice was determined by microscopic examination of stained blood smears. Statistical significance of protection was determined by a one-way ANOVA followed by Tukey's post hoc test. Two intravenous immunizations produced 94% protection to mosquito bite challenge; intradermal immunization produced 78% protection, while intradermal immunization accompanied by "tape-stripping" produced 94% protection. There were no statistically significant differences in degree of protective immunity between immunizations done by intravenous versus intradermal injection. The use of a sub-microlitre syringe for intradermal injections yielded excellent protective immunity. ID-immunization with large numbers of radiation-attenuated P. yoelii sporozoites led to levels of protective immunity comparable to those achieved by IV-immunization. It remains to be determined whether an adjuvant
Alves, Renato V; Brandão, Fabiano H; Aquino, José E P; Carvalho, Maria R M S; Giancoli, Suzana M; Younes, Eduado A P
Intradermal nevi are common benign pigmented skin tumors. Their occurrence within the external auditory canal is uncommon. The clinical and pathologic features of an intradermal nevus arising within the external auditory canal are presented, and the literature reviewed.
Fatma Sayed Mohamed
Full Text Available Aim: The present work was established in order to investigate the effect of ultra-corn administration on the immune response of vaccinated calves with FMD bivalent oil vaccine. Material and Methods: Forty calves; at a private farm in EL-Fayoum Governorate (Locality A; were divided into 4 groups where the first group was vaccinated with the locally produced FMD bivalent oil vaccine alone while the 2nd, 3rd and 4th group were vaccinated with the same vaccine simultaneously with the inoculation of 1, 1.5 and 2mL/100kg body weight of ultra-corn respectively to estimate the antibody titer, the suitable dose and effect of ultra-corn as immunostimulant using SNT and ELISA. Also after that used the effective and lowest dose of ultra-corn simultaneously with the vaccine in comparison with the vaccine alone by using 26 calves (Locality B to study the efficacy of ultra-corn simultaneously with vaccine and the vaccine alone via challenge test using the virulent FMDV serotype A,O. Results: Tested serum samples obtained on week intervals post vaccination of all calve groups were subjected for estimation of induced FMD antibodies type A and O using serum neutralization test (SNT and enzyme linked immune sorbent assay (ELISA. Both tests indicate that 1.5mL, 2mL of ultra-corn enhanced the immune response of vaccinated calves exhibiting higher and longer immunity than those received the vaccine alone. In addition 26 calves housed under restrict hygienic measures at Veterinary Serum and Vaccine Research Institute, were divided into 4 groups where group-1 of 10 calves were vaccinated with the bivalent FMD vaccine alone and group-2 was vaccinated with the same vaccine simultaneously with 1.5mL of ultra-corn while group 3 and 4 were kept as control for the challenge test. On the 4th week post vaccination group 1, 2 of these animals was subdivided into 2 subgroups where the challenge test was carried out against type A in a subgroup and O in other subgroup. SNT and
Çokçalışkan, Can; Türkoğlu, Tunçer; Uzunlu, Ergün; Sareyyüpoğlu, Beyhan; Hancı, İbrahim; İpek, Ahmet; Arslan, Abdullah; Babak, Ayca; İldeniz, Gülnur; Gülyaz, Veli
Foot-and-mouth disease is one of the most important viral diseases of cloven-hoofed animals. Mass vaccination is an effective method to control the disease and is frequently utilized in endemic regions. Sufficient protection of young animals is important in mass vaccination campaigns. Maternal antibodies negatively affect the success of vaccination. Hence, determination of the optimal vaccination age is crucial for the uninterrupted protection of young animals. This study was performed to identify the effect of vaccine potency and booster administration on serum neutralizing antibody titers of calves with different levels of maternal antibodies. Calves (n = 111) on a state farm were used in this study. Oil adjuvant foot-and-mouth disease vaccines with 3 PD50 and 6 PD50 potencies were used with or without booster administration. Serum samples were collected each month up to day 120 postvaccination. Virus neutralization tests were used to measure the serum neutralizing antibody titers and estimate the protection period by using pre-determined cut-off values for protection. The results revealed that a vaccination with a 6 PD50 potency vaccine, preferably followed by a booster dose, should be used to overcome maternal immunity for incessant protection.
Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M
Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral
Rashmi Ranjan Das
Full Text Available Prophylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children.A systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. Randomized controlled trials (RCTs comparing prophylactic antipyretic treatment versus placebo post-vaccination in children ≤ 6 years of age were included. Two reviewers independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data [PROSPERO registration: CRD42014009717].Of 2579 citations retrieved, a total of 13 RCTs including 5077 children were included in the review. Prophylactic antipyretic administration significantly reduced the febrile reactions (≥ 38.0 °C after primary and booster vaccinations. Though there were statistically significant differences in the antibody responses between the two groups, the prophylactic PCM group had what would be considered protective levels of antibodies to all of the antigens given after the primary and booster vaccinations. No significant difference in the nasopharyngeal carriage rates (short-term and long-term of H. influenzae or S. pneumoniae serotypes was found between the prophylactic and no prophylactic PCM group. There was a significant reduction in the local and systemic symptoms after primary, but not booster vaccinations.Though prophylactic antipyretic administration leads to relief of the local and systemic symptoms after primary vaccinations, there is a reduction in antibody responses to some vaccine antigens without any effect on the nasopharyngeal carriage rates of S. pneumoniae & H. influenza serotypes. Future trials and surveillance programs should also aim at
Co-administration of an adjuvanted FeLV vaccine together with a multivalent feline vaccine to cats is protective against virulent challenge with feline leukaemia virus, calicivirus, herpes virus and panleukopenia virus
In conclusion, the results from this study demonstrate that concurrent or simultaneous administration of these two vaccines resulted in equivalent efficacy; both vaccine administration regimes showing significant differences in clinical scores or lower levels of persistent antigenaemia when compared to non-vaccinated control cats following challenge.
Ayala-Montiel, Octavio; Mascareñas de los Santos, César; García-Hernández, Delfino; Rendón-Muñiz, Jorge; García-Olvera, Laura
Pneumonia is the principal cause of morbidity and mortality in PEMEX medical services. Vaccination against influenza is 72% effective in preventing hospitalizations and 87% effective in preventing deaths related to this virus, and vaccination against pneumococcus is 60% effective in preventing invasive diseases by this microorganism. ACIP recommends use of both vaccines simultaneously in adults over 65 years of age. To describe the frequency, duration and severity of local and systemic reactions related to the simultaneous administration of vaccines against influenza and pneumococcus in adults over 55 years of age, and compare with reactions related to influenza vaccine. Two hundred-thirty two adults over 55 years of age were randomly assigned to two groups, group A (114 subjects) received influenza vaccine, group B (118 subjects) received influenza and pneumococcus vaccines simultaneously. Comparing the number of subjects with local reactions on the right arm between groups A and B (17 subjects vs. 27 subjects), differences were not statistically significative (p = 0.121). Systemic reactions were not statistically significative either (p = 0.126) when results were compared between both groups (30 from group A vs. 42 for group B). Simultaneous administration of influenza and pneumococcus vaccines has proven to be safety. In the absence of contraindications, there is no reason for not offering both vaccines in the same medical visit.
Gadad, Bharathi S; Li, Wenhao; Yazdani, Umar; Grady, Stephen; Johnson, Trevor; Hammond, Jacob; Gunn, Howard; Curtis, Britni; English, Chris; Yutuc, Vernon; Ferrier, Clayton; Sackett, Gene P; Marti, C Nathan; Young, Keith; Hewitson, Laura; German, Dwight C
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.
Vargas-Pino, Fernando; Gutiérrez-Cedillo, Verónica; Canales-Vargas, Erick J; Gress-Ortega, Luis R; Miller, Lowell A; Rupprecht, Charles E; Bender, Scott C; García-Reyna, Patricia; Ocampo-López, Juan; Slate, Dennis
Mexico serves as a global model for advances in rabies prevention and control in dogs. The Mexican Ministry of Health (MMH) annual application of approximately 16 million doses of parenteral rabies vaccine has resulted in significant reductions in canine rabies during the past 20 years. One collateral parameter of rabies programs is dog population management. Enhanced public awareness is critical to reinforce responsible pet ownership. Surgical spaying and neutering remain important to prevent reproduction, but are impractical for achieving dog population management goals. GonaCon™, an anti-gonadotropin releasing hormone (GnRH) vaccine, was initially tested in captive female dogs on the Navajo Nation, 2008. The MMH led this international collaborative study on an improved formulation of GonaCon™ in captive dogs with local representatives in Hidalgo, Mexico in 2011. This study contained 20 bitches assigned to Group A (6 control), Group B (7 GonaCon™), and Group C (7 GonaCon™ and rabies vaccine). Vaccines were delivered IM. Animals were placed under observation and evaluated during the 61-day trial. Clinically, all dogs behaved normally. No limping or prostration was observed, in spite of minor muscle atrophy post-mortem in the left hind leg of dogs that received GonaCon™. Two dogs that began the study pregnant give birth to healthy pups. Dogs that received a GonaCon™ injection had macro and microscopic lesions consistent with prior findings, but the adverse injection effects were less frequent and lower in intensity. Both vaccines were immunogenic based on significant increases in rabies virus neutralizing antibodies and anti-GnRH antibodies in treatment Groups B and C. Simultaneous administration of GonaCon™ and rabies vaccine in Group C did not affect immunogenicity. Progesterone was suppressed significantly in comparison to controls. Future studies that monitor fertility through multiple breeding cycles represent a research need to determine the
Surendiran, Adithan; Kaku, Mayur V; Adithan, Chandrasekaran
Medication error is one of the important causes of preventable adverse drug reactions. It can occur in the form of administration of a wrong drug, in the wrong dose, to the wrong patient, in an unsuitable dosage form, for the wrong duration or by using an inappropriate route of administration. Intradermal skin testing for cloxacillin hypersensitivity is done at low doses to check for drug allergy. In this report, three patients were given 50 times higher dose of cloxacillin than recommended for skin testing, resulting in pain and necrosis at the site of injection. The error occurred due to wrong dilution of the drug as done by a nursing intern. Some reasons for this could be overtime working, under trained staff, unsupervised nursing interns, complicated and unclear protocols, interpersonal communication gap between health care professionals and also poor availability of ideal resources. Pharmacovigilance centers must alert health care professionals about the significance of reporting medication errors through bulletins and journals.
Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark
Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered
Clement A Meseda
Full Text Available The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification. The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1 elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that
Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau.
Fisker, Ane Bærent; Ravn, Henrik; Rodrigues, Amabelia; Østergaard, Marie Drivsholm; Bale, Carlito; Benn, Christine Stabell; Aaby, Peter
Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects. In 2007-2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6-23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors. While DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20-8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79-33.4). In line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality. Copyright © 2013 Elsevier Ltd. All rights reserved.
Budimir, Natalija; de Haan, Aalzen; Meijerhof, Tjarko; Gostick, Emma; Price, David A.; Huckriede, Anke; Wilschut, Jan
Background Development of influenza vaccines capable of inducing broad protection against different virus subtypes is necessary given the ever-changing viral genetic landscape. Previously, we showed that vaccination with whole inactivated virus (WIV) induces heterosubtypic protection against lethal
Full Text Available Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY conjugated to the carrier protein keyhole limpet hemocyanin (OXY-KLH has been shown to attenuate the antinociceptive effects of oxycodone. Here, the vaccine's ability to prevent acquisition of intravenous (i.v. oxycodone self-administration was studied in rats. Effects of vaccination on oxycodone-induced changes in the expression of several genes within the mesolimbic system, which are regulated by chronic opiate use, were also examined. Vaccination with OXY-KLH reduced the proportion of rats acquiring i.v. self-administration of oxycodone under a fixed ratio (FR 3 schedule of reinforcement compared to control rats immunized with the unconjugated KLH carrier protein. Vaccination significantly reduced the mean number of infusions at FR3, total number of infusions, and total oxycodone intake during the entire protocol. Compared to oxycodone self-administering control rats immunized with the carrier alone, rats vaccinated with the OXY-KLH immunogen showed increased levels of adenylate cyclase 5 (Adcy5 and decreased levels of early growth response protein 2 (Egr2 and the early immediate gene c-Fos in the striatum. These data suggest that vaccination with OXY-KLH can attenuate the reinforcing effects of oxycodone at a clinically-relevant exposure level. Analysis of mRNA expression identified some addiction-relevant markers that may be of interest in understanding oxycodone effects or the protection provided by vaccination.
Vescovo, Paul; Rettby, Nils; Ramaniraka, Nirinarilala; Liberman, Julie; Hart, Karen; Cachemaille, Astrid; Piveteau, Laurent-Dominique; Zanoni, Reto; Bart, Pierre-Alexandre; Pantaleo, Giuseppe
In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Muhammad Ehsanul Hoque
Full Text Available Cervical cancer is a preventable public health problem. The two new human papillomavirus (HPV vaccines are available but not accessible to everyone in South Africa, as they are very expensive. This study aimed to investigate educated peoples acceptability regarding HPV vaccination. This was a cross-sectional survey conducted among 146 master of business administration students by self-administered, anonymous questionnaire. The majority (74% of the participants ever heard of cervical cancer, but only 26.2% heard about HPV. After reading the fact information regarding cervical cancer and HPV, the intention to vaccinate their daughters increased from 88% to 97.2% (P=0.003. The majority (75.4% indicated that HPV vaccination should be given before their daughters are mature enough to understand about sex, and 80.3% reported that they will discuss matters related to sex with their daughters if their daughters want to know about the vaccine. Those who did not want to vaccinate their daughters highlighted that they want more information regarding safety of the vaccine which might change their decision towards HPV vaccination. A health education information method can increase the vaccination acceptance rate in South Africa.
Bartlett, Diana L; Washington, Michael L; Bryant, Amanda; Thurston, Norman; Perfili, Christine A
Our objective was to investigate the potential cost savings of immunization information systems (IIS) in performing some administrative tasks associated with the federal Vaccines for Children (VFC) program at the state and practice levels. VFC is an entitlement program providing free vaccine to eligible children. We timed the staff of the Utah Department of Health (UDOH) and 72 private VFC practices for administrative VFC-related tasks from September 2003 through March 2004. Time measurements included time for practices to produce VFC reports and for UDOH staff to assess practice coverage levels and process VFC reports manually or via the Utah Statewide Immunization Information System (USIIS). Median cost savings to the state health department could be as much as $11 740 annually. Utah VFC practices could save up to a maximum of $446 annually per practice by using USIIS for VFC tasks. If applied to the 218 enrolled private practices statewide, this would result in a median total cost savings of $17,615 ($15,519 for reports and $2,096 for pulling medical charts).
van der Maaden, Koen; Heuts, Jeroen; Camps, Marcel; Pontier, Maria; Terwisscha van Scheltinga, Anton; Jiskoot, Wim; Ossendorp, Ferry; Bouwstra, Joke
Recent studies have shown that intradermal vaccination has great potential for T cell-mediated cancer immunotherapy. However, classical intradermal immunization with a hypodermic needle and syringe has several drawbacks. Therefore, in the present study a digitally controlled hollow microneedle injection system (DC-hMN-iSystem) with an ultra-low dead volume was developed to perform micro-injections (0.25-10μL) into skin in an automated manner. A synthetic long peptide derived from human papilloma virus formulated in cationic liposomes, which was used as a therapeutic cancer vaccine, was administered intradermally by using the DC-hMN-iSystem. Fused silica hollow microneedles with an inner diameter of 50μm and a bevel length of 66±26μm were successfully fabricated via hydrofluoric acid etching. Upon piercing these microneedles into the skin using a protrusion length of 400μm, microneedles were inserted at a depth of 350±55μm. Micro-injections of 1-10μL had an accuracy between 97 and 113% with a relative standard deviation (RSD) of 9%, and lower volumes (0.25 and 0.5μL) had an accuracy of 86-103% with a RSD of 29% in ex vivo human skin. Intradermal administration of the therapeutic cancer vaccine via micro-injections induced strong functional cytotoxic and T-helper responses in mice, while requiring much lower volumes as compared to classical intradermal immunization. In conclusion, by using the newly developed DC-hMN-iSystem, very low vaccine volumes can be precisely injected into skin in an automated manner. Thereby, this system shows potential for minimally-invasive and potentially pain-free therapeutic cancer vaccination. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar
This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns
Wallace, Aaron S; Mantel, Carsten; Mayers, Gill; Mansoor, Osman; Gindler, Jacqueline S; Hyde, Terri B
An increasing proportion of childhood immunization visits include administration of multiple injections. Future introduction of vaccines to protect against multiple diseases will further increase the number of injections at routine immunization childhood visits, particularly in developing countries that are still scaling up introductions. Parental and healthcare provider attitudes toward multiple injections may affect acceptance of recommended vaccines, and understanding these attitudes may help to inform critical decisions about vaccine introduction. We conducted a systematic review of the literature to examine factors underlying reported parental and healthcare provider concerns and practices related to administration of multiple injections during childhood vaccination visits. Forty-four articles were identified; 42 (95%) were from high income countries, including 27 (61%) from the USA. Providers and parents report concerns about multiple injections, which tend to increase with increasing numbers of injections. Common parental and provider concerns included apprehension about the pain experienced by the child, worry about potential side effects, and uncertainty about vaccine effectiveness. Multiple studies reported that a positive provider recommendation to the parent and a high level of concern about the severity of the target disease were significantly associated with parental acceptance of all injections. Providers often significantly overestimated parental concerns about multiple injections. Providers may play a critical role in the decision for a child to receive all recommended injections. Their overestimation of parental concerns may lead them to postpone recommended vaccinations, which may result in extra visits and delayed vaccination. More research is needed on interventions to overcome provider and parental concern about multiple injections, particularly in developing countries. Published by Elsevier Ltd.
Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants.
Tanaka, Yoshiyuki; Yokokawa, Ruriko; Rong, Han Shi; Kishino, Hiroyuki; Stek, Jon E; Nelson, Margaret; Lawrence, Jody
Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.
Kita, Yoko; Hashimoto, Satomi; Nakajima, Toshihiro; Nakatani, Hitoshi; Nishimatsu, Shiho; Nishida, Yasuko; Kanamaru, Noriko; Kaneda, Yasuhumi; Takamori, Yasushi; McMurray, David; Tan, Esterlina V.; Cang, Marjorie L.; Saunderson, Paul; Dela Cruz, E.C.; Okada, Masaji
Purpose: Multi-drug resistant tuberculosis (MDR-TB) and extremely drug resistant (XDR) TB are big problems in the world. We have developed novel TB therapeutic vaccines, HVJ-Envelope/HSP65 + IL-12 DNA vaccine (HSP65-vaccine), granulysin vaccine and killer specific secretory protein of 37kDa (Ksp37) vaccine. Methods and Results: HSP65 vaccine showed strong therapeutic effect against both MDR-TB and XDR-TB in mice. Intradermal immunization of HSP65-vaccine showed stronger therapeutic effect against TB than intramuscular or subcutaneous immunization. Furthermore, the synergistic therapeutic effect was observed when the vaccine was administrated in combination with Isoniazid (INH), which is a first line drug for chemotherapy. The combination of types of vaccines (HSP65- and granulysin- vaccines) also showed synergistic therapeutic effect. In the monkey model, granulysin-vaccine prolonged the survival period after the infection of TB and long-term survival was observed in vaccine-treated group. We examined the potential of two kinds of novel DNA vaccines (Ksp37-vaccine and granulysin-vaccine). Both vaccines augmented in vivo differentiation of CTL against TB. We measured the amount of Ksp37 protein in human serum and revealed that the level of Ksp37 protein of patients with tuberculosis was lower than that of healthy volunteers. Therefore, we established Ksp37 transgenic mice as well as granulysin transgenic mice to elucidate the function of those proteins. Both transgenic mice were resistant to TB infection. Conclusion: These data indicate the potential of combinational therapy; the combination of two DNA vaccines or combination of DNA vaccine with antibiotic drug. Thus, it will provide a novel strategy for the treatment of MDR-TB. PMID:23249609
Yaguchi, K; Ohgitani, T; Noro, T; Kaneshige, T; Shimizu, Y
One hundred and twenty 30-day-old specific-pathogen-free chickens were inoculated with the liposomal inactivated avian pathogenic Escherichia coli (APEC) vaccine by eye drop or coarse spraying. All of the chickens produced anti-lipopolysaccharide antibodies of the IgG subclass in their sera as well as IgA antibodies in their oral mucus. The results demonstrated a rise in antibodies in the serum of chickens administered the APEC vaccine through nonparenteral mucosal routes. Bacterial counts in the blood decreased, and clinical signs were moderated in the vaccinated chickens after challenge with a strain of APEC. No harmful effects from the vaccination were observed. The liposomal inactivated APEC vaccine described in this paper would contribute to a practical method of control for avian colibacillosis.
vaccination, delivery methods, electroporation, molecular adjuvants, intramuscular, intradermal 1. Introduction The Filoviridae family of viruses is...a malaria DNA vaccine by immunization with a needle-free jet device. Vaccine, 2001. 20(1-2): p. 275-80. 20. Choi, A.H., et al., Protection of mice
Guevara, Ana; Cabello, Robinson; Woelber, Linn; Moreira, Edson Duarte; Joura, Elmar; Reich, Olaf; Shields, Christine; Ellison, Misoo C; Joshi, Amita; Luxembourg, Alain
The 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11/16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPV-related vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the generation of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5years post-vaccination. A subset of subjects (N=150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card. HPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1week and 1month post-dose 4 were 1.25-4.10 and 1.65-4.88-fold higher, respectively, than levels observed 1month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1week and 1month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated. A three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting. Clinical Trials.gov Identifier:NCT00543543. Copyright © 2017 Elsevier Ltd. All rights reserved.
Drinka, Paul J
Influenza vaccination is estimated to be 50-68% efficacious in preventing pneumonia, hospitalisation or death in nursing home residents. Large culture-proven outbreaks may occur despite high resident vaccination rates. There is, therefore, a significant role for concurrent administration of influenza vaccination and antiviral therapy. The use of antiviral treatment and chemoprophylaxis requires community reporting of viral isolates, and contingency plans for rapid case identification and application of antiviral therapy. Clinicians must react quickly to control a highly infectious seasonal pathogen that may strike as an explosive outbreak. This situation is unique in geriatric practice. Current antiviral treatment should be administered within 48 hours of symptom onset, and is more efficacious if administered within 12 hours. In the case of an explosive institutional outbreak, a 1-day delay in prophylaxis may allow infection of many residents with a potentially fatal illness. Influenza must be differentiated from other respiratory viruses or syndromes. Grouped rapid diagnostic tests can aid laboratory confirmation. Antiviral agents include the M(2) inhibitors, amantadine and rimantadine, active against influenza A, and the neuraminidase inhibitors, zanamivir and oseltamivir, active against influenza A and B. In our experience, influenza B illness is as severe as influenza A. All agents have similar efficacy as treatment and prophylaxis against sensitive strains. When M(2) inhibitors are used simultaneously within an enclosed space (i.e. household or nursing home) as both treatment and prophylaxis, resistant strains may emerge that limit prophylactic efficacy. When M(2) inhibitors are administered to suspected cases (residents or staff) in institutions, precautions against secretion are especially important to diminish the risk of transmission of resistant virus. Rimantadine has been shown to have significantly fewer CNS adverse events compared with amantadine
Vandermeulen, Gaëlle; Vanvarenberg, Kevin; De Beuckelaer, Ans; De Koker, Stefaan; Lambricht, Laure; Uyttenhove, Catherine; Reschner, Anca; Vanderplasschen, Alain; Grooten, Johan; Préat, Véronique
We investigated the influence of the site of administration of DNA vaccine on the induced immune response. DNA vaccines were administered by electroporation at three different sites: tibial cranial muscle, abdominal skin and ear pinna. Aiming to draw general conclusions about DNA vaccine delivery, we successively used several plasmids encoding either luciferase and ovalbumin as models or gp160 and P1A as vaccines against HIV and P815 mastocytoma, respectively. Low levels and duration of luciferase transgene expression were observed after electroporation of the abdominal skin, partly explaining its lower immunogenic performance as compared to the other sites of administration. Analyses of OT-I CD8+ and OT-II CD4+ T cell responses highlighted the differential impact of the delivery site on the elicited immune response. Muscle electroporation induced the strongest humoral immune response and both muscle and ear pinna sites induced cellular immunity against gp160. Ear pinna delivery generated the highest level of CTL responses against P1A but electroporation of muscle and ear pinna were equally efficient in delaying P815 growth and improving mice survival. The present study demonstrated that the site of administration is a key factor to be tested in the development of DNA vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.
Liu, Xiaohong; Zhang, Hua; Gao, Yuan; Zhang, Yang; Wu, Haizhen; Zhang, Yuanxing
Vaccine is one of the efficient candidates to prevent fish disease through activating host immune response in aquaculture. Actually, several vaccines are often administered with adjuvants to increase immunostimulation, especially for some water-based formalin-killed vaccines. However, side effects are inevitable after vaccination of some adjuvants. Therefore, exploration for effective and harmless aquatic adjuvants is urgently needed. In this study, immunoprotection of a formalin-inactivated Vibrio anguillarum vaccine applied with chitosan oligosaccharide (COS) was analyzed. High levels of protection were achieved in zebrafish and turbot vaccinated with inactivated vaccine and COS (RPS of 89.0 ± 4.5% and 80.0 ± 6.9%) compared with fish vaccinated with inactivated vaccine alone (RPS of 47.8 ± 6.6% and 64.7 ± 5.8%) at 4 week post vaccination. Moreover, high antibody reaction and cross-protection against Vibrio alginolyticus and Vibrio harveyi were observed of turbot vaccinated with inactivated vaccine and COS. In conclusion, COS can enhance immunoprotection of a formalin-inactivated V. anguillarum vaccine, significantly activate humoral immune response of host, and be benefit for inhibition against pathogens. Therefore, COS would be a potential adjuvant for aquatic vaccine design in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.
Hegde, Nagendra R; Kaveri, Srinivas V; Bayry, Jagadeesh
Despite remarkable progress in the control of infectious diseases through vaccination, better delivery systems have been poorly explored. There is renewed interest in the discovery of novel vaccines and adjuvants owing to emerging and reemerging diseases and the burden and complexity of chronic infectious diseases. Conversely, the need for rapid local, regional, mucosal or parenteral bioavailability has led to advances in delivery systems and devices. Here, we present recent developments in the field of non-invasive cutaneous delivery of vaccines for infectious diseases. Transdermal delivery using microneedles could revolutionize the way prophylactic interventions for infectious diseases are carried out in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.
Dilana López Borbón
Full Text Available The aim of this research had been in evidence if the administrative order of the immune-biological has implications in the pain response from an infant during vaccination. The pain could promote a negative perspective related to the immunization, especially in children and their parents. For that reason, an adequate pain management during vaccination could have as a consequence a better acceptance of the immunization program by the society. During the research, the methodology that had been applied was based evidence clinical practice. Firstly, It had been necessary formulated a PICO question. Secondly, the best articles had been found after searching in databases as PubMed, Medline, Cochrane and Tripdata base. These five articles had been evaluated through the critical analysis using CASPe template. As a result, the order in the administration of immune-biological has consequences in the pain response of the child. To conclude, it is important to note that the order of immune-biological and child pain response have relating. So, it is necessary to administrate the painful vaccine at the end in order to have a better management of childhood pain. Additionally, it is important to do more researches about the specific order that vaccines would be administrated.
Mahdavi, Mehdi; Mavandadnejad, Faranak; Yazdi, Mohammad H; Faghfuri, Elnaz; Hashemi, Hura; Homayouni-Oreh, Somayeh; Farhoudi, Ramin; Shahverdi, Ahmad R
Hepatitis B virus (HBV) infection is known as a life-threatening liver infection and leads to chronic liver disease if left untreated. Nevertheless, the prevalence of HBV infection has been reduced by an approved vaccination approach using recombinant Hepatitis B surface Antigen (HBsAg) and Alum, known as the HBV vaccine. Alum can be used as an adjuvant to increase HBsAg immunogenicity as a strong Th2 stimulator. There is a vital need to stimulate Th1 immunity by HBsAg vaccination; however, the present vaccine does not induce a prophylactic immune response in some groups. The main aim of the present study was to induce a Th1 cytokine pattern and stimulate an immune response after HBsAg vaccination. Experimental mice were fed selenium nanoparticles (SeNPs) and were later immunized with 5μg of Hepatitis B Vaccine. After a period of 30 days, the experimental animals were given two booster doses of SeNPs during their vaccination course. Group one, i.e., the control vaccine group, was only administered the HBsAg vaccine. The two treated groups, Groups 2 and 3, were daily fed different doses of SeNPs (100μg and 200μg, respectively) via gavage. Group four was considered the control group and was only given phosphate buffered saline (PBS). Lymphocyte proliferation, IFN-γ and IL-4 levels, total antibody and the isotypes of IgG1, IgG2a, IgG2b, and IgM were measured by Enzyme Linked Immunosorbent Assay (ELISA). The administration of SeNPs and the HBs antigen vaccine affected the lymphocyte proliferation; moreover, the total antibody responses also increased the IFN-γ level and induced a Th1 response. The present study proposed that the administration of SeNPs with a conventional HBs antigen vaccine induces a better immune response with a Th1 bias. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Rebmann, Terri; Loux, Travis M; Lew, Daphne; Wakefield, Mary
Introduction Little is known about childcare staff's and parents' uptake of and attitudes towards pertussis vaccine. Methods Questionnaires were distributed to St. Louis parents and childcare staff in fall, 2014. Parents versus staff and vaccinated versus unvaccinated individuals' beliefs regarding pertussis vaccine were compared using chi square tests. Multivariate logistic regressions were run to develop predictive models for staff's and parents' vaccine uptake. Results Overall, 351 parents and staff from 23 agencies participated (response rate = 32%). Parents were more likely than staff to have received pertussis vaccine (66.5 vs. 45.8%, X 2 = 12.5, p < .001). Predictors for staff vaccination included willingness to get vaccinated even if there was a cost (OR 6.6; CI 1.8-24.6; p < .01), awareness of vaccination recommendations (OR 5.2; CI 1.2-22.8; p < .05), and healthcare provider recommendation (OR 4.2; CI 1.2-15.1; p < .05). Parents' predictors of vaccination included perceived importance of vaccination (OR 9.9; CI 4.1-23.8; p < .001), healthcare provider recommendation (OR 4.6; CI 1.7-12.6; p < .01), believing vaccination is effective (OR 4.4; CI 1.1-18.0; p < .05), and knowing where to get vaccine (OR 3.5; CI 1.5-8.1; p < .01). Among unvaccinated staff (n = 52), 74.5% (n = 38) and 70.0% (n = 35) would receive pertussis vaccine if it were offered free of charge and onsite, respectively. Conclusions for Practice Childcare staff's and parents' pertussis vaccine uptake was higher than overall U.S. rates, though significantly lower than the Global Pertussis Initiative target. Implementing an education campaign and providing free vaccine on-site are likely to result in increased vaccine uptake.
BİRİCİK, Halil Selçuk
The objective of this study was to compare the efficacy of autogenous vaccine, autohaemotherapy and autogenous vaccine-autohaemotherapy combinations in the treatment of bovine papillomatosis. The study was performed on 27 cattle aged between 1 and 2.5 years. The animals were divided into three groups (nine in each group) as autogenous vaccine, autohaemotherapy and autogenous vaccine-autohaemotherapy combinations. Doses of 10 ml per animal were injected subcutaneously at weekly intervals, a t...
Vrdoljak, Anto; McGrath, Marie G; Carey, John B; Draper, Simon J; Hill, Adrian V S; O'Mahony, Conor; Crean, Abina M; Moore, Anne C
Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.
Wang, Sheena H; Thompson, Afton L; Hickey, Anthony J; Staats, Herman F
Dry powder vaccine formulations have proved effective for induction of systemic and mucosal immune responses. Here we review the use of dry vaccines for immunization in the respiratory tract. We discuss techniques for powder formulation, manufacture, characterization and delivery in addition to methods used for evaluation of stability and safety. We review the immunogenicity and protective efficacy of dry powder vaccines as compared to liquid vaccines delivered by mucosal or parenteral routes. Included is information on mucosal adjuvants and mucoadhesives that can be used to enhance nasal or pulmonary dry vaccines. Mucosal immunization with dry powder vaccines offers the potential to provide a needle-free and cold chain-independent vaccination strategy for the induction of protective immunity against either systemic or mucosal pathogens.
Rebmann, T; Baskin, C R; Loux, T M; Wakefield, M
Study objectives were to assess parents' and childcare agency staff's uptake of and attitudes/beliefs related to hepatitis A vaccine. Cross-sectional survey. Questionnaires were administered to parents and staff in 23 St. Louis childcare agencies between September and December 2014. Categorical data were compared using Chi-squared test. Multivariate logistic regression, stratified by staff vs parents, was used to find predictors of hepatitis A vaccine uptake. In total, 351 staff and parents participated (response rate = 32%). More staff than parents had been offered or recommended to receive hepatitis A vaccine by a healthcare provider (55.4% vs 36.6% and 53.3% vs 28.7%, respectively; P = .001 for both). More staff than parents received hepatitis A vaccine (85.3% vs 67.5%, Chi-squared test = 11.0, P vaccine uptake included being aware of CDC vaccination recommendations (OR = 11.2, CI = [1.4-91], P vaccinated (OR = 8.1, CI = [1.8-36.8], P vaccination policy (OR = 4.8, CI = [1.2-19.7], P vaccine uptake included being offered the vaccine by a healthcare provider (OR = 4.3, CI = [1.3-4.9], P vaccination recommendations (OR = 4.0, CI = [2.0-8.0], P vaccine previously (OR = 2.5, CI = [1.3-4.9], P vaccine, though staff immunization rates are at the minimum needed to reach herd immunity levels. Having employers encourage vaccination, offer free vaccine, or make vaccine available onsite could increase staff vaccination rates. Public health should partner with childcare agencies to increase staff vaccine uptake, which could result in community herd immunity. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Full Text Available Live-attenuated oral rotavirus (RV vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV using the human rotavirus strain CDC-9 (G1P through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn piglets challenged with virulent Wa G1P human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.
Full Text Available Asian countries bear the greatest burden of the disease, with a majority (59% of rabies-related deaths occurring in Asia. In order to promote best practices, we summarized national human vaccination guidelines across this region, to highlight differences and similarities and to discuss the aspects that would benefit from updates. National management guidelines for rabies were retrieved from various sources to extract information on rabies pre- and post-exposure prophylaxis (PrEP, and PEP, booster vaccination, and route of administration. Rabies guidelines recommendations for wound management and PrEP across Asia are broadly aligned to the World Health Organization (WHO guidelines. For PEP, the 5-dose Essen, and the 4-dose Zagreb are the regimens of choice for intramuscular (IM, and the Thai Red Cross regimen for intradermal (ID, administration. Several national guidelines have yet to endorse ID vaccine administration. Most guidelines recommend rabies immunoglobulin in category III exposures. Booster recommendations are not included in all guidelines, with limited clarity on booster requirement across the spectrum of risk of rabies exposure. In conclusion, national recommendations across Asian countries differ and while some guidelines are closely aligned to the WHO recommendations, resource-saving ID administration and use of rational abbreviated schedules have yet to be endorsed.
Starita, Chiara; Gavazza, Alessandra; Lubas, George
The aim of the study was to evaluate hematological, biochemical, and serological findings in healthy canine blood donors after the administration of CaniLeish® vaccine. Twenty-seven client-owned dogs were included in the study and arranged into 3 groups according to the vaccination stage. Complete blood count (CBC) with blood smear examination, serum biochemical profile (SBP), serum protein electrophoresis (SPE), and serological tests for L. infantum were performed at different times. Additionally, in a subgroup of dogs IgA, IgM, and IgG were quantified. No statistical significance for CBC and SBP was found. In 10.7% of cases slight hyperproteinemia occurred. In SPE absolute values β-1-globulins (Group 2 and Group 2-3) and β-2-globulins (Group 3) were found modified (P < 0.05). IgG values were statistically different (P < 0.05) 6-8 months after the third immunisation (Group 2) and IgM and IgG values were statistically different after 2 months (Group 3). IFAT positive samples were 20.8% (Group 1), 15.0% (Group 2), and 52.8% (Group 3). Speed Leish K™ tests were always negative. The modifications found were probably attributed to the development of immune or inflammatory response due to the vaccine. Administration of CaniLeish vaccine in canine blood donors could be a safe practice and did not affect their health status.
Full Text Available The aim of the study was to evaluate hematological, biochemical, and serological findings in healthy canine blood donors after the administration of CaniLeish® vaccine. Twenty-seven client-owned dogs were included in the study and arranged into 3 groups according to the vaccination stage. Complete blood count (CBC with blood smear examination, serum biochemical profile (SBP, serum protein electrophoresis (SPE, and serological tests for L. infantum were performed at different times. Additionally, in a subgroup of dogs IgA, IgM, and IgG were quantified. No statistical significance for CBC and SBP was found. In 10.7% of cases slight hyperproteinemia occurred. In SPE absolute values β-1-globulins (Group 2 and Group 2-3 and β-2-globulins (Group 3 were found modified (P<0.05. IgG values were statistically different (P<0.05 6–8 months after the third immunisation (Group 2 and IgM and IgG values were statistically different after 2 months (Group 3. IFAT positive samples were 20.8% (Group 1, 15.0% (Group 2, and 52.8% (Group 3. Speed Leish K™ tests were always negative. The modifications found were probably attributed to the development of immune or inflammatory response due to the vaccine. Administration of CaniLeish vaccine in canine blood donors could be a safe practice and did not affect their health status.
Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro® and a varicella vaccine (VARIVAX® by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial
Full Text Available Abstract Background When this trial was initiated, the combined measles, mumps and rubella (MMR vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro® and a varicella vaccine (VARIVAX® compared with the subcutaneous route. Methods An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374 or subcutaneously (SC group, n = 378. Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit. Results Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of ≥ 1.25 gpELISA units/ml. Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (≤ 2.5 cm. There was a trend for lower rates of injection-site erythema and swelling in the IM group. The incidence and nature of systemic adverse events were comparable for the two routes
Meyer, Martin Willy; Zachariae, Claus Otto Carl; Garvey, Lene Heise
Anaphylactic shock after intradermal injection of corticosteroid Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to carboxymethylcellulose in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has...
... REQUIREMENTS Diagnostics and Reagents § 113.409 Tuberculin—PPD Bovis, Intradermic. Tuberculin—PPD Bovis... index Classification 440 mm 2 or greater Satisfactory. Between 360 mm 2 and 440 mm 2 Inconclusive. Less...
Mittal, Ankit; Schulze, Kai; Ebensen, Thomas; Weissmann, Sebastian; Hansen, Steffi; Guzmán, Carlos A; Lehr, Claus-Michael
Transfollicular antigen delivery through the intact skin is an interesting new avenue for needle-free vaccination. The aim of this work was to evaluate the potential of surfactant based inverse micellar sugar glass nanoparticles (IMSG NPs) as a delivery system for such purpose. To this end, we evaluated the strength and type of immune response elicited after administration of IMSG NPs containing the model antigen ovalbumin (OVA) by intranasal, transfollicular or intradermal route. Furthermore, we explored the possibility of improving the immune response elicited by co-encapsulating the adjuvant bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) and OVA within one particulate carrier system. The study showed enhanced stability and encapsulation efficacy of the antigen when encapsulated in IMSG NPs in comparison to polylactic-co-glycolic acid (PLGA) and chitosan-PLGA NPs. Moreover, by transfollicular delivery, IMSG NPs showed enhanced follicular uptake in comparison to OVA solution or OVA-loaded chitosan-PLGA NPs. While the immune response stimulated after intranasal administration was negligible, significant humoral and cellular responses were observed after immunization via transfollicular and intradermal route. This holds particularly true when OVA and c-di-AMP were co-encapsulated in IMSG NPs, as compared to OVA±c-di-AMP solution or OVA-loaded IMSG NPs without adjuvantation. The results of this study underscore not only the potential of transfollicular vaccination, but also the need for optimized nanocarriers and adjuvants. Copyright © 2015 Elsevier B.V. All rights reserved.
Influenza Vaccine Effectiveness in Preventing Influenza A(H3N2)-Related Hospitalizations in Adults Targeted for Vaccination by Type of Vaccine: A Hospital-Based Test-Negative Study, 2011–2012 A(H3N2) Predominant Influenza Season, Valencia, Spain
Puig-Barberà, Joan; García-de-Lomas, Juan; Díez-Domingo, Javier; Arnedo-Pena, Alberto; Ruiz-García, Montserrat; Limón-Ramírez, Ramón; Pérez-Vilar, Silvia; Micó-Esparza, José Luis; Tortajada-Girbés, Miguel; Carratalá-Munuera, Concha; Larrea-González, Rosa; Beltrán-Garrido, Juan Manuel; Otero-Reigada, Maria del Carmen; Mollar-Maseres, Joan; Correcher-Medina, Patricia; Schwarz-Chavarri, Germán; Gil-Guillén, Vicente
Background Most evidence of the effectiveness of influenza vaccines comes from studies conducted in primary care, but less is known about their effectiveness in preventing serious complications. Here, we examined the influenza vaccine effectiveness (IVE) against hospitalization with PCR-confirmed influenza in the predominant A(H3N2) 2011–2012 influenza season. Methods A hospital-based, test-negative study was conducted in nine hospitals in Valencia, Spain. All emergency admissions with a predefined subset of symptoms were eligible. We enrolled consenting adults age 18 and over, targeted for influenza vaccination because of comorbidity, with symptoms of influenza-like-illness within seven days of admission. We estimated IVE as (1-adjusted vaccination odds ratio)*100 after accounting for major confounders, calendar time and recruitment hospital. Results The subjects included 544 positive for influenza A(H3N2) and 1,370 negative for influenza admissions. Age was an IVE modifying factor. Regardless of vaccine administration, IVE was 72% (38 to 88%) in subjects aged under 65 and 21% (−5% to 40%) in subjects aged 65 and over. By type of vaccine, the IVE of classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was 68% (12% to 88%). The IVE for intradermal and virosomal influenza vaccines, used in subjects aged 65 and over, was 39% (11% to 58%) and 16% (−39% to 49%), respectively. Conclusions The split-influenza vaccine was effective in preventing influenza-associated hospitalizations in adults aged under 65. The intradermal vaccine was moderately effective in those aged 65 and over. PMID:25392931
Influenza vaccine effectiveness in preventing influenza A(H3N2-related hospitalizations in adults targeted for vaccination by type of vaccine: a hospital-based test-negative study, 2011-2012 A(H3N2 predominant influenza season, Valencia, Spain.
Full Text Available Most evidence of the effectiveness of influenza vaccines comes from studies conducted in primary care, but less is known about their effectiveness in preventing serious complications. Here, we examined the influenza vaccine effectiveness (IVE against hospitalization with PCR-confirmed influenza in the predominant A(H3N2 2011-2012 influenza season.A hospital-based, test-negative study was conducted in nine hospitals in Valencia, Spain. All emergency admissions with a predefined subset of symptoms were eligible. We enrolled consenting adults age 18 and over, targeted for influenza vaccination because of comorbidity, with symptoms of influenza-like-illness within seven days of admission. We estimated IVE as (1-adjusted vaccination odds ratio*100 after accounting for major confounders, calendar time and recruitment hospital.The subjects included 544 positive for influenza A(H3N2 and 1,370 negative for influenza admissions. Age was an IVE modifying factor. Regardless of vaccine administration, IVE was 72% (38 to 88% in subjects aged under 65 and 21% (-5% to 40% in subjects aged 65 and over. By type of vaccine, the IVE of classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was 68% (12% to 88%. The IVE for intradermal and virosomal influenza vaccines, used in subjects aged 65 and over, was 39% (11% to 58% and 16% (-39% to 49%, respectively.The split-influenza vaccine was effective in preventing influenza-associated hospitalizations in adults aged under 65. The intradermal vaccine was moderately effective in those aged 65 and over.
Li, Yun; Xu, Yu-Ling; Lai, Yan-Ni; Liao, Shang-Hui; Liu, Ni; Xu, Pei-Ping
Vaccination is the most efficient means for protection against influenza. However, the various vaccines have low efficacy to protect against pandemic strains because of antigenic drift and recombination of influenza virus. Adjuvant therapy is one of the attempts to improve influenza vaccine effective cross-protection against influenza virus infection. Our previous study confirmed that 1,8-cineole inhibits the NF-κB, reduces pro-inflammatory cytokines, and relieves the pathological changes of viral pneumonia in mice infected with influenza virus. 1,8-cineole, administered via intranasal (i.n.) route, may also have the capacity to be an adjuvant of the influenza vaccine. This study was designed to investigate the potential use of i.n. co-administration of 1,8-cineole, a major component of the Eucalyptus essential oils, with influenza vaccine and whether could provide cross-protection against influenza virus infection in a mouse model. I.n. co-administration of 1,8-cineole in two doses (6.25 and 12.5 mg/kg) with influenza vaccine was investigated in a mouse model in order to see whether it could provide cross-protection against influenza virus infection. The mice were intranasally immunized three times at the 0, 7 and 14 day with vaccine containing 0.2 µg hemagglutinin (HA) and/or without 1,8-cineole. Seven days after the 3rd immunization dose, the mice were infected with 50 µl of 15 LD50 (50% mouse lethal dose) influenza virus A/FM/1/47 (H1N1). On day 6 post-infection, 10 mice per group were sacrificed to collect samples, to take the body weight and lung, and detect the viral load, pathological changes in the lungs and antibody, etc. The collected samples included blood serum and nasal lavage fluids. In addition, the survival experiments were carried out to investigate the survival of mice. Mice i.n. inoculated with influenza vaccine and 12.5 mg/kg 1,8-cineole increased the production of influenza-specific serum immunoglobulin (Ig) G2a antibodies
Labadie J; Sundermann LC; Rumke HC; the DPT-IPV Hib vaccine study group; LVO; LVM; LCB; LBA; LPO
Results are presented of a multi-center clinical study into the antibody formation following two vaccination regimens with simultaneous and combined administration of DPT-IPV and Hib PRP-T vaccines. 543 infants were recruited from 42 baby clinics in Apeldoorn, Capelle and Rotterdam. The antibody
Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C
Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797
Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX™ adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques.
DiStefano, Daniel; Antonello, Joseph M; Bett, Andrew J; Medi, Muneeswara B; Casimiro, Danilo R; ter Meulen, Jan
There is a need for novel rabies vaccines suitable for short course, pre- and post-exposure prophylactic regimens which require reduced doses of antigen to address the current worldwide supply issue. We evaluated in rhesus macaques the immunogenicity of a quarter-dose of a standard rabies vaccine formulated with Merck's amorphous aluminum hydroxylphosphate sulfate adjuvant, the saponin-based ISCOMATRIX™ adjuvant, or a synthetic TLR9 agonist. All adjuvants significantly increased the magnitude and durability of the humoral immune response as measured by rapid fluorescent focus inhibition test (RFFIT). Several three-dose vaccine regimens resulted in adequate neutralizing antibody of ≥ 0.5 IU/ml earlier than the critical day seven post the first dose. Rabies vaccine with ISCOMATRIX™ adjuvant given at days 0 and 3 resulted in neutralizing antibody titers which developed faster and were up to one log10 higher compared to WHO-recommended intramuscular and intradermal regimens and furthermore, passive administration of human rabies immunoglobulin did not interfere with immunogenicity of this reduced dose, short course vaccine regimen. Adjuvantation of whole-killed rabies vaccine for intramuscular injection may therefore be a viable alternative to intradermal application of non-adjuvanted vaccine for both pre- and post-exposure regimens. Copyright © 2013 Elsevier Ltd. All rights reserved.
... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. ...
Nayak, Tapas R; Wang, Hao; Pant, Aakansha; Zheng, Minrui; Junginger, Hans; Goh, Wei Jiang; Lee, Choon Keong; Zou, Shui; Alonso, Sylvie; Czarny, Bertrand; Storm, Gert; Sow, Chorng Haur; Lee, Chengkuo; Pastorin, Giorgia
Intradermal delivery of antigens for vaccination is a very attractive approach since the skin provides a rich network of antigen presenting cells, which aid in stimulating an immune response. Numerous intradermal techniques have been developed to enhance penetration across the skin. However, these methods are invasive and/or affect the skin integrity. Hence, our group has devised zinc oxide (ZnO) nano-rods for non-destructive drug delivery. Chemical vapour deposition was used to fabricate aligned nano-rods on ZnO pre-coated silicon chips. The nano-rods' length and diameter were found to depend on the temperature, time, quality of sputtered silicon chips, etc. Vertically aligned ZnO nano-rods with lengths of 30-35 µm and diameters of 200-300 nm were selected for in vitro human skin permeation studies using Franz cells with Albumin-fluorescein isothiocyanate (FITC) absorbed on the nano-rods. Fluorescence and confocal studies on the skin samples showed FITC penetration through the skin along the channels formed by the nano-rods. Bradford protein assay on the collected fluid samples indicated a significant quantity of Albumin-FITC in the first 12 h. Low antibody titres were observed with immunisation on Balb/c mice with ovalbumin (OVA) antigen coated on the nano-rod chips. Nonetheless, due to the reduced dimensions of the nano-rods, our device offers the additional advantage of excluding the simultaneous entrance of microbial pathogens. Taken together, these results showed that ZnO nano-rods hold the potential for a safe, non-invasive, and painless intradermal drug delivery.
Tapas R. Nayak
Full Text Available Intradermal delivery of antigens for vaccination is a very attractive approach since the skin provides a rich network of antigen presenting cells, which aid in stimulating an immune response. Numerous intradermal techniques have been developed to enhance penetration across the skin. However, these methods are invasive and/or affect the skin integrity. Hence, our group has devised zinc oxide (ZnO nano-rods for non-destructive drug delivery. Chemical vapour deposition was used to fabricate aligned nano-rods on ZnO pre-coated silicon chips. The nano-rods’ length and diameter were found to depend on the temperature, time, quality of sputtered silicon chips, etc. Vertically aligned ZnO nano-rods with lengths of 30–35 µm and diameters of 200–300 nm were selected for in vitro human skin permeation studies using Franz cells with Albumin-fluorescein isothiocyanate (FITC absorbed on the nano-rods. Fluorescence and confocal studies on the skin samples showed FITC penetration through the skin along the channels formed by the nano-rods. Bradford protein assay on the collected fluid samples indicated a significant quantity of Albumin-FITC in the first 12 h. Low antibody titres were observed with immunisation on Balb/c mice with ovalbumin (OVA antigen coated on the nano-rod chips. Nonetheless, due to the reduced dimensions of the nano-rods, our device offers the additional advantage of excluding the simultaneous entrance of microbial pathogens. Taken together, these results showed that ZnO nano-rods hold the potential for a safe, non-invasive, and painless intradermal drug delivery.
Osinubi, M O V; Wu, X; Franka, R; Niezgoda, M; Nok, A J; Ogunkoya, A B; Rupprecht, C E
Enhancing DNA vaccine effectiveness remains a challenge, especially if the desired goal is immunization efficacy after a single dose. The glycoprotein gene from the rabies virus Evelyn-Rokitnicki-Abelseth (ERA) strain was modified by mutation at amino acid residue 333 from arginine to glutamine. The modified and original unmodified glycoprotein genes were cloned separately and developed as DNA vaccines for immunization in mice. The intramuscular (IM) route using a single dose (100 microg) of a modified DNA vaccine showed virus neutralizing antibody induction by d30, and 80% of the mice survived a challenge in which 100% of unvaccinated controls succumbed. Similar results were obtained using a single dose (10 microg) by the intradermal (ID) route with one-tenth amount of the DNA administered. Administration of single dose of DNA vaccine with unmodified G did not result in the production of detectable levels of virus neutralizing antibody by d30. The results of the IM and the ID routes of administration were statistically significant (Prabies virus strain may be an ideal candidate for DNA vaccine efficacy enhancement.
Maaden, Koen van der
Conventional vaccines are administered intramuscularly or subcutaneously via hypodermic needles, causing pain and stress. Since the skin is a powerful immune organ, it is not surprising that intradermal injections result in potent immune responses. However, they are relatively difficult to perform
Full Text Available A number of factors influence the development of tolerance, including the nature, concentration and mode of antigen presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding antigens from HIV-1 and influenza virus were administered intravenously to pregnant mice. At 9.5 days post conception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with trans-placental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger antigen-specific immune responses than controls and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA vaccinated mothers confer the antigen-specific immunity to their progeny. Here we describe the methods in detail as they relate to our previously published work.
Resultados de teste tuberculínico efetuado três meses após vacinação, por meio do BCG administrado pela via intradérmica, de pessoas com idades diversas e residentes em São Paulo, SP (Brasil Results of tuberculin tests performed three months after BCG intradermal vaccination on persons of various ages residing in S. Pauto, Brazil
Vicente Amato Neto
Full Text Available Foram analisados os resultados de teste tuberculínico, efetuado três meses após vacinação com BCG (amostra Moreau-Rio de Janeiro, pela via intradérmica. A casuística correspondeu a 7.790 pessoas, incluindo as de grupo pertinente ao primeiro trimestre de vida e merecedor, atualmente, de especial atenção. Ficou constatada, globalmente, a percentagem de positividade de 69%. Houve apreciação, especifica e detalhada, referente a indivíduos de idades diversas, e a abordagem do tema tornou-se oportuna em face ao interesse que esse tipo de imunização vem despertando no Brasil e, também, em virtude da necessidade de coletar informes aptos a apoiar trabalhos profiláticos.Results of tuberculin skin tests performed three months after intradermal vaccination with the Moreau-Rio de Janeiro strain of BCG were analyzed. The tests were made upon 7,790 persons, including a group of infants in their first trimester of life, a delicate and obviously necessary object of attention today. The percentage of positive reactors in the whole population group tested was 69%. A detailed analysis of the reactiveness in the different age groups was carried out. Moreover, that this study is opportune has been stressed not only because of the rising interest in Brazil in this type of immunization but also because of the need to compile information supporting prophylactic action.
Lafeber AF; van der Klis FRM; Marzec AHJO; Labadie J; van Ommen R; Strieder TG; Berbers GAM; LVO
In deze studie is de gebruikelijke en in de bijsluiter geadviseerde subcutane toedieningsroute van het BMR vaccin vergeleken met intramusculaire toediening, zowel wat betreft veiligheid als immunogeniciteit. De studie populatie bestond uit 14 maanden oude kinderen uit Amersfoort of Utrecht die in
Mašek, Josef; Lubasová, Daniela; Lukáč, Róbert; Turánek-Knotigová, Pavlína; Kulich, Pavel; Plocková, Jana; Mašková, Eliška; Procházka, Lubomír; Koudelka, Štěpán; Sasithorn, Nongnut; Gombos, Jozsef; Bartheldyová, Eliška; Hubatka, František; Raška, Milan; Miller, Andrew D; Turánek, Jaroslav
Nanofibre-based mucoadhesive films were invented for oromucosal administration of nanocarriers used for delivery of drugs and vaccines. The mucoadhesive film consists of an electrospun nanofibrous reservoir layer, a mucoadhesive film layer and a protective backing layer. The mucoadhesive layer is responsible for tight adhesion of the whole system to the oral mucosa after application. The electrospun nanofibrous reservoir layer is intended to act as a reservoir for polymeric and lipid-based nanoparticles, liposomes, virosomes, virus-like particles, dendrimers and the like, plus macromolecular drugs, antigens and/or allergens. The extremely large surface area of nanofibrous reservoir layers allows high levels of nanoparticle loading. Nanoparticles can either be reversibly adsorbed to the surface of nanofibres or they can be deposited in the pores between the nanofibres. After mucosal application, nanofibrous reservoir layers are intended to promote prolonged release of nanoparticles into the submucosal tissue. Reversible adsorption of model nanoparticles as well as sufficient mucoadhesive properties were demonstrated. This novel system appears appropriate for the use in oral mucosa, especially for sublingual and buccal tissues. To prove this concept, trans-/intramucosal and lymph-node delivery of PLGA-PEG nanoparticles was demonstrated in a porcine model. This system can mainly be used for sublingual immunization and the development of "printed vaccine technology". Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available Rachel E Rizal,1,* Rishi P Mediratta,1,* James Xie,1 Swetha Kambhampati,1 Kelsey Hills-Evans,1 Tamara Montacute,1 Michael Zhang,1 Catherine Zaw,2 Jimmy He,2 Magali Sanchez,2 Lauren Pischel1 1Stanford University School of Medicine, Stanford, CA, USA; 2Stanford University, Stanford, CA, USA *These authors contributed equally to this work Abstract: Many national organizations call for medical students to receive more public health education in medical school. Nonetheless, limited evidence exists about successful service-learning programs that administer preventive health services in nonclinical settings. The Flu Crew program, started in 2001 at the Stanford University School of Medicine, provides preclinical medical students with opportunities to administer influenza immunizations in the local community. Medical students consider Flu Crew to be an important part of their medical education that cannot be learned in the classroom. Through delivering vaccines to where people live, eat, work, and pray, Flu Crew teaches medical students about patient care, preventive medicine, and population health needs. Additionally, Flu Crew allows students to work with several partners in the community in order to understand how various stakeholders improve the delivery of population health services. Flu Crew teaches students how to address common vaccination myths and provides insights into implementing public health interventions. This article describes the Stanford Flu Crew curriculum, outlines the planning needed to organize immunization events, shares findings from medical students' attitudes about population health, highlights the program’s outcomes, and summarizes the lessons learned. This article suggests that Flu Crew is an example of one viable service-learning modality that supports influenza vaccinations in nonclinical settings while simultaneously benefiting future clinicians. Keywords: immunizations, vaccine delivery, vaccinations
Meyer, Martin Willy; Zachariae, Claus Otto Carl; Garvey, Lene Heise
Anaphylactic shock after intradermal injection of corticosteroid Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to carboxymethylcellulose in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has...... previously been reported. We report a case of a 52-year-old woman with prurigo nodularis of Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40 mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient was advised to avoid future parenteral exposure to CMC...
Schmid, Michael A; Kauffman, Elizabeth; Payne, Anne; Harris, Eva; Kramer, Laura D
Mosquito-transmitted pathogens are among the leading causes of severe disease and death in humans. Components within the saliva of mosquito vectors facilitate blood feeding, modulate host responses, and allow efficient transmission of pathogens, such as Dengue, Zika, yellow fever, West Nile, Japanese encephalitis, and chikungunya viruses, as well as Plasmodium parasites, among others. Here, we describe standardized methods to assess the impact of mosquito-derived factors on immune responses and pathogenesis in mouse models of infection. This protocol includes the generation of mosquito salivary gland extracts and intradermal inoculation of mouse ears. Ultimately, the information obtained from using these techniques can help reveal fundamental mechanisms of interaction between pathogens, mosquito vectors, and the mammalian host. In addition, this protocol can help establish improved infection challenge models for pre-clinical testing of vaccines or therapeutics that take into account the natural route of transmission via mosquitoes.
Rizal, Rachel E; Mediratta, Rishi P; Xie, James; Kambhampati, Swetha; Hills-Evans, Kelsey; Montacute, Tamara; Zhang, Michael; Zaw, Catherine; He, Jimmy; Sanchez, Magali; Pischel, Lauren
Many national organizations call for medical students to receive more public health education in medical school. Nonetheless, limited evidence exists about successful servicelearning programs that administer preventive health services in nonclinical settings. The Flu Crew program, started in 2001 at the Stanford University School of Medicine, provides preclinical medical students with opportunities to administer influenza immunizations in the local community. Medical students consider Flu Crew to be an important part of their medical education that cannot be learned in the classroom. Through delivering vaccines to where people live, eat, work, and pray, Flu Crew teaches medical students about patient care, preventive medicine, and population health needs. Additionally, Flu Crew allows students to work with several partners in the community in order to understand how various stakeholders improve the delivery of population health services. Flu Crew teaches students how to address common vaccination myths and provides insights into implementing public health interventions. This article describes the Stanford Flu Crew curriculum, outlines the planning needed to organize immunization events, shares findings from medical students' attitudes about population health, highlights the program's outcomes, and summarizes the lessons learned. This article suggests that Flu Crew is an example of one viable service-learning modality that supports influenza vaccinations in nonclinical settings while simultaneously benefiting future clinicians.
A delayed, Tuberculin type response to intradermal (ID) test with benzathine penicillin is described in a 50 year old female. She did not develop any sign of drug reaction on receiving.intramuscular injection of that drug. None of the 65 patients who were studied in detail for the ID test response to various penicillins showed such a delayed response.
Full Text Available A delayed, Tuberculin type response to intradermal (ID test with benzathine penicillin is described in a 50 year old female. She did not develop any sign of drug reaction on receiving.intramuscular injection of that drug. None of the 65 patients who were studied in detail for the ID test response to various penicillins showed such a delayed response.
Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...
Gelfond, M L; Ivanov, V G; Semiglazov, V F; Vorotnikov, V V; Belousova, T A; Zhiltsova, E K; Ivanova, O A; Ermilova, E V; Fedosov, S I
There are presented results of photodynamic therapy (PDT) for patients with chemo- and radioresistant intradermal metastases of breast cancer using the matrix light-emitting diodes apparatus. To all patients prior to irradiation there was performed fluorescence diagnostics to assess the accumulation of the photosensitizer of chlorine series and photobleaching during PDT. The size of the irradiation area was 400 sm, the total dose of irradiation was 250J/cm2. PDT was accompanied by mild pain, which was stopped by administration of non-narcotic analgesics. Complete regression of intradermal lesions was registered in 2 of 4 cases, partial response was observed in 1 patient and the progression of the process in 1 case.
Hoft, D F; Xia, M; Zhang, G L; Blazevic, A; Tennant, J; Kaplan, C; Matuschak, G; Dube, T J; Hill, H; Schlesinger, L S; Andersen, P L; Brusic, V
Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4 + memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.Mucosal Immunology advance online publication 30 August 2017; doi:10.1038/mi.2017.67.
Immunogenicity and safety of an inactivated quadrivalent influenza vaccine co-administered with a 23-valent pneumococcal polysaccharide vaccine versus separate administration, in adults ≥50years of age: Results from a phase III, randomized, non-inferiority trial.
Ofori-Anyinam, Opokua; Leroux-Roels, Geert; Drame, Mamadou; Aerssens, Annelies; Maes, Cathy; Amanullah, Arshad; Schuind, Anne; Li, Ping; Jain, Varsha K; Innis, Bruce L
We compared co-administration versus separate administration of an inactivated quadrivalent influenza vaccine (IIV4) with a 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults at high risk of complications of influenza and pneumococcal infection. This phase III, placebo-controlled, observer-blind trial (NCT02218697) was conducted in France and Belgium during the 2014-2015 influenza season. Adults≥50years of age meeting their country's vaccination recommendations were randomized 1:1 to co-administration or separate administration. Immunogenicity was assessed by hemagglutination inhibition (HI) titers for IIV4 and 22F-inhibition ELISA for PPV23. Co-primary objectives were to demonstrate non-inferiority of co-administration versus separate administration in terms of geometric mean titer (GMT) ratio for each influenza strain in the IIV4 and geometric mean concentration (GMC) ratio for six pneumococcal serotypes (1, 3, 4, 7F, 14, 19A) in the PPV23 in the per-protocol cohort (N=334). The study met its co-primary objectives, with the upper limit of the 95% confidence interval of the GMT and GMC ratios (separate administration over co-administration) being ≤2.0 for all four antigens of the IIV4 and the six pre-selected serotypes of the PPV23, respectively. Immunogenicity of the IIV4 and PPV23 was similar regardless of administration schedule. In a post hoc analysis pooling participants ≥60years of age from the co-administration and separate administration groups, IIV4 immunogenicity was similar in higher risk adults with comorbidities (diabetes; respiratory, heart, kidney, liver, or neurological diseases; morbid obesity) versus those without. Both vaccines had an acceptable safety and reactogenicity profile; pain was the most common symptom, occurring more often with co-administration than separate administration. The IIV4 and PPV23 can be co-administered without reducing antibody responses reflecting protection against influenza or pneumococcal disease
Cet imposant volume constitue un registre des cours magistraux tenus par l’auteur à l’École supérieure allemande des sciences administratives de Spire, enrichis des résultats de travaux scientifiques menés principalement à l'Institut Allemand de Recherche en Administration Publique (Deutsches Forschungsinstitut für öffentliche Verwaltung Speyer, FÖV). Il s’agit donc d’une entreprise au long cours, destinée à apporter un nouvel éclairage (quasi ?) exhaustif sur l’administration publique : son ...
Laurichesse, H.; Gourdon, F.; Smits, H. L.; Abdoe, T. H.; Estavoyer, J. M.; Rebika, H.; Pouliquen, P.; Catalina, P.; Dubray, C.; Beytout, J.
The safety and immunogenicity of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae was evaluated in 84 volunteers according to the route of administration, i.e., subcutaneous (SC) or intramuscular (IM), in a double-blind randomised trial. The volunteers
Sim, H-L; Tan, K-Y
Open haemorrhoidectomy has been associated with considerable postoperative pain and discomfort. Perianal intradermal injection of methylene blue has been shown to ablate perianal nerve endings and may bring about temporary pain relief after haemorrhoidectomy. We hypothesized that the administration of intradermal methylene blue would reduce postoperative pain during the initial period after surgery. A randomized, prospective, single-blind placebo-controlled trial was conducted. Patients were randomized to intradermal injection at haemorrhoidectomy of either 4 ml 1% methylene blue and 16 ml 0.5% marcaine or of 16 ml 0.5% marcaine and 4 ml saline prior to surgical dissection. Patients were asked to fill in a pain diary with a visual analogue scale. The primary outcome measure was pain score and analgesic use. Secondary outcomes were complications. There were 37 patients in the methylene blue arm and 30 patients in the placebo arm. There were no statistically significant differences in the sex, type of haemorrhoid, number of haemorrhoids excised, duration of surgery or hospital stay. The mean pain scores were significantly lower and the use of paracetamol was also significantly less in the methylene blue group during the first three postoperative days. The risk ratio of acute urinary retention occurring when methylene blue was not used was 2.320 (95% CI 1.754-3.067). Other complication rates were not significantly different. Perianal intradermal injection of methylene blue was useful in reducing the initial postoperative pain of open haemorrhoidectomy. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.
Roestenberg, Meta; Bijker, Else M.; Sim, B. Kim Lee; Billingsley, Peter F.; James, Eric R.; Bastiaens, Guido J. H.; Teirlinck, Anne C.; Scholzen, Anja; Teelen, Karina; Arens, Theo; van der Ven, André J. A. M.; Gunasekera, Anusha; Chakravarty, Sumana; Velmurugan, Soundarapandian; Hermsen, Cornelus C.; Sauerwein, Robert W.; Hoffman, Stephen L.
Controlled human malaria infection with sporozoites is a standardized and powerful tool for evaluation of malaria vaccine and drug efficacy but so far only applied by exposure to bites of Plasmodium falciparum (Pf)-infected mosquitoes. We assessed in an open label Phase 1 trial, infection after intradermal injection of respectively 2,500, 10,000, or 25,000 aseptic, purified, vialed, cryopreserved Pf sporozoites (PfSPZ) in three groups (N = 6/group) of healthy Dutch volunteers. Infection was safe and parasitemia developed in 15 of 18 volunteers (84%), 5 of 6 volunteers in each group. There were no differences between groups in time until parasitemia by microscopy or quantitative polymerase chain reaction, parasite kinetics, clinical symptoms, or laboratory values. This is the first successful infection by needle and syringe with PfSPZ manufactured in compliance with regulatory standards. After further optimization, the use of such PfSPZ may facilitate and accelerate clinical development of novel malaria drugs and vaccines. PMID:23149582
Full Text Available Melanocytic nevi in the bone metaplasia is not a common case. The majority of these lesions tend to be located in the upper part of the body, as in our case. There is a higher incidence of females. In the pathogenesis usually is thought to develop seconder damage of the hair follicles. We report a 46-year-old woman who presented a case of osseous metaplasia within a benign intradermal melanocytic nevus was excised from the face.
Cupera, Z; Krupka, V; Jiran, E
A new application method was developed and tested for the immunoprophylaxis of rabbits against myxomatosis using a live MXT vaccine. This new application method--injection of the ear with a special double needle--is very simple and easy. Its use enables a five-fold increase in vaccination doses as compared with subcutaneous application while the amount of vaccine remains the same. In laboratory this method with the MXT vaccine secured a 98.2% protection of the vaccinated animals. One vaccination dose contains 18.1 to 37.2 PD50. Eleven months from a single vaccination by injecting the ear, 83% of the rabbits still remained protected against experimental infection. With the use of the new application method of injecting the ear with the special double needle, the live MXT vaccine against myxomatosis in rabbits represents an effective, easily practicable and economically advantageous direction in the immunoprophylaxis of rabbits against myxomatosis.
Travis S Hottes
Full Text Available Administrative databases provide efficient methods to estimate influenza vaccine effectiveness (IVE against severe outcomes in the elderly but are prone to intractable bias. This study returns to one of the linked population databases by which IVE against hospitalization and death in the elderly was first assessed. We explore IVE across six more recent influenza seasons, including periods before, during, and after peak activity to identify potential markers for bias.Acute respiratory hospitalization and all-cause mortality were compared between immunized/non-immunized community-dwelling seniors ≥65 years through administrative databases in Manitoba, Canada between 2000-01 and 2005-06. IVE was compared during pre-season/influenza/post-season periods through logistic regression with multivariable adjustment (age/sex/income/residence/prior influenza or pneumococcal immunization/medical visits/comorbidity, stratification based on prior influenza immunization history, and propensity scores. Analysis during pre-season periods assessed baseline differences between immunized and unimmunized groups. The study population included ∼140,000 seniors, of whom 50-60% were immunized annually. Adjustment for key covariates and use of propensity scores consistently increased IVE. Estimates were paradoxically higher pre-season and for all-cause mortality vs. acute respiratory hospitalization. Stratified analysis showed that those twice consecutively and currently immunized were always at significantly lower hospitalization/mortality risk with odds ratios (OR of 0.60 [95%CI0.48-0.75] and 0.58 [0.53-0.64] pre-season and 0.77 [0.69-0.86] and 0.71 [0.66-0.77] during influenza circulation, relative to the consistently unimmunized. Conversely, those forgoing immunization when twice previously immunized were always at significantly higher hospitalization/mortality risk with OR of 1.41 [1.14-1.73] and 2.45 [2.21-2.72] pre-season and 1.21 [1.03-1.43] and 1.78 [1
A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.
Sayeed, Md Abu; Bufano, Meagan Kelly; Xu, Peng; Eckhoff, Grace; Charles, Richelle C; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md Rasheduzzaman; Berger, Amanda; Gonzalez-Escobedo, Geoffrey; Mandlik, Anjali; Bhuiyan, Taufiqur Rahman; Leung, Daniel T; LaRocque, Regina C; Harris, Jason B; Calderwood, Stephen B; Qadri, Firdausi; Vann, W F; Kováč, Pavol; Ryan, Edward T
Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization. Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model. We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.
A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.
Md Abu Sayeed
Full Text Available Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP component of lipopolysaccharide (LPS.Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc. We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg, vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1, effect of an adjuvant, and route of immunization.Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg. We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.
Full Text Available Abstract Background Type I interferons (IFNs exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV or HIV. Results Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4+ T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4+ T cell responses were enhanced by IFNα subtypes. Conclusions Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4+ T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.
Segal, Lawrence; Morelle, Danielle; Kaaber, Kari; Destexhe, Eric; Garçon, Nathalie
The human papillomavirus (HPV)-16/18 vaccine (Cervarix®) is a prophylactic vaccine for the prevention of cervical cancer. The vaccine contains recombinant virus-like particles assembled from the L1 major capsid proteins of the cervical cancer-causing viral types HPV-16 and HPV-18, and Adjuvant System 04 (AS04), which contains the immunostimulant MPL and aluminium salt. To evaluate potential local and systemic toxic effects of the HPV-16/18 vaccine or AS04 alone, three repeated-dose studies were performed in rabbits and rats. One rabbit study also included a single-dose evaluation. In rabbits (~2.5 kg), the full human dose (HD) of the vaccine was evaluated (0.5 ml per injection site), and in rats (~250 g), 1/5 HD of vaccine was evaluated, corresponding to ≥ 12 times the dosage in humans relative to body weight. In both animal models, the treatment-related changes included a slight transient increase in the number of circulating neutrophils as well as a local inflammatory reaction at the injection site. These treatment-related changes were less pronounced after four doses of AS04 alone than after four doses of the HPV-16/18 vaccine. Additional treatment-related changes in the rat included lower albumin/globulin ratios and microscopic signs of inflammation in the popliteal lymph nodes. In both animal models, 13 weeks after the fourth dose, recovery was nearly complete, although at the injection site in some animals there were signs of discoloration, muscle-fibre regeneration and focal points of macrophage infiltration. Therefore, in these non-clinical models, the single and repeated dose administrations of the HPV-16/18 vaccine or AS04 alone were safe and well tolerated. Copyright © 2015 John Wiley & Sons, Ltd.
Wright, Glenn; Chow, Joan
Because of the rapid development of genital warts (GW) after infection, monitoring GW trends may provide early evidence of population-level human papillomavirus (HPV) vaccine effectiveness. Trends in GW diagnoses were assessed using public family planning administrative data. Between 2007 and 2010, among females younger than 21 years, these diagnoses decreased 35% from 0.94% to 0.61% (Ptrend < .001). Decreases were also observed among males younger than 21 years (19%); and among females and males ages 21-25 (10% and 11%, respectively). The diagnoses stabilized or increased among older age groups. HPV vaccine may be preventing GW among young people. PMID:22420808
Bauer, Heidi M; Wright, Glenn; Chow, Joan
Because of the rapid development of genital warts (GW) after infection, monitoring GW trends may provide early evidence of population-level human papillomavirus (HPV) vaccine effectiveness. Trends in GW diagnoses were assessed using public family planning administrative data. Between 2007 and 2010, among females younger than 21 years, these diagnoses decreased 35% from 0.94% to 0.61% (P(trend) < .001). Decreases were also observed among males younger than 21 years (19%); and among females and males ages 21-25 (10% and 11%, respectively). The diagnoses stabilized or increased among older age groups. HPV vaccine may be preventing GW among young people.
Sadleir, P H M; Russell, T; Clarke, R C; Maycock, E; Platt, P R
Sugammadex is a selective binding agent for aminosteroid neuromuscular blockers whose use is increasing in anaesthetic practice. We present three cases of severe anaphylaxis coincident with sugammadex administration. Subsequent intradermal testing confirmed sugammadex as the triggering agent, with all patients having positive skin responses to a 1:100 dilution of the standard 100 mg/ml solution and two out of three having a positive response to a 1:1000 dilution. As all patients were administered sugammadex to reverse neuromuscular blockade with rocuronium, we considered that sugammadex-rocuronium complexes were a potential unique allergen. In the two patients who were additionally tested with a rocuronium-sugammadex (3.6:1 molecular ratio) mixture, the wheal-and-flare response was significantly attenuated.
Full Text Available As a new category of therapeutics for skin diseases including atopic dermatitis (AD, nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery.
Hultström, Michael; Roxhed, Niclas; Nordquist, Lina
The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines. © 2014 Diabetes Technology Society.
Kwon, Ki Mun; Lim, Su-Min; Choi, Seulgi; Kim, Da-Hee; Jin, Hee-Eun; Jee, Grace; Hong, Kee-Jong; Kim, Joo Young
Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.
... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a doctor...
Odutayo, O. J.
Full Text Available This study investigated the effects of supplemental vitamins and varying administration periods on growth performance and antibody titre of broiler chickens vaccinated against Newcastle Disease (ND. A total of 300 unvaccinated against ND Arbor Acre day-old chicks were used for the study for 8 wk. Birds were brooded together on day 1 of age, and 30 chicks were selected randomly for evaluating the maternally derived antibody titre against ND. At 2 days of age, the remaining 270 chicks were divided based on weight equalization into 9 treatment groups and replicated thrice. The 9 treatments consisted of a factorial arrangement of 4 supplemental vitamins (A, C, E and combination of A, C, E and 2 periods of administration (3 days pre- and post-ND vaccinations with a control. The birds were managed intensively throughout the experimental period, ND vaccines were administered on the 5th (i/o and 24th (Lasota day of age, respectively. Supplemental combined vitamins A, C and E at 0.15, 16.67 and 3.03 mg/kg, respectively, resulted in higher (P < 0.05 final body weight of 1785.00 g/bird and better feed conversion ratio (FCR of 2.89. Also, birds fed vitamin A supplemented diet 3 d pre-i/o vaccine had higher (p<0.05 serum antibody titre (75.20 against ND while higher (p<0.05 serum antibody titre (741.33 was also obtained in birds fed diet supplemented with vitamin E 3 d post-Lasota vaccination. Conclusively, broiler chickens diets can be supplemented with combined vitamins A, C, and E for better growth performance measured as final body weight and FCR, in addition, vitamins A (0.45mg/kg and E (9.1mg/kg dietary supplementation at 3 d pre-i/o and 3 d post-Lasota vaccines, respectively, can be adopted for improved antibody production.
Hashem, Fahima M; Fahmy, Sahar A; El-Sayed, Aly M; Al-Sawahli, Majid M
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.
Meyer, Martin Willy; Zachariae, Claus; Garvey, Lene Heise
nodularis of Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40 mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient was advised to avoid future parenteral exposure to CMC. This case highlights the need to examine excipients in severe cases of drug......Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to CMC in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has previously been reported. We report a case of a 52-year-old woman with prurigo...... allergy....
Meyer, Martin Willy; Zachariae, Claus; Garvey, Lene Heise
Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to CMC in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has previously been reported. We report a case of a 52-year-old woman with prurigo...... nodularis of Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40 mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient was advised to avoid future parenteral exposure to CMC. This case highlights the need to examine excipients in severe cases of drug...
Meyer, Martin Willy; Zachariae, Claus; Garvey, Lene Heise
Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to CMC in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has previously been reported. We report a case of a 52-year-old woman with prurigo...... nodularis of Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40 mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient was advised to avoid future parenteral exposure to CMC. This case highlights the need to examine excipients in severe cases of drug...
Administration of Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and Avian Beta Defensin as Adjuvants in Inactivated Inclusion Body Hepatitis Virus and its Hexon Protein-Based Experimental Vaccine Formulations in Chickens.
Dar, Arshud; Tipu, Masroor; Townsend, Hugh; Potter, Andy; Gerdts, Volker; Tikoo, Suresh
Inclusion body hepatitis (IBH) is one of the major infectious diseases adversely affecting the poultry industry of the United States and Canada. Currently, no effective and safe vaccine is available for the control of IBH virus (IBHV) infection in chickens. However, based on the excellent safety and immunogenic profiles of experimental veterinary vaccines developed with the use of new generation adjuvants, we hypothesized that characterization of vaccine formulations containing inactivated IBHV or its capsid protein hexon as antigens, along with poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and avian beta defensin 2 (ABD2) as vaccine adjuvants, will be helpful in development of an effective and safe vaccine formulation for IBH. Our data demonstrated that experimental administration of vaccine formulations containing inactivated IBHV and a mixture of PCEP with or without ABD2 as an adjuvant induced significantly higher antibody responses compared with other vaccine formulations, while hexon protein-based vaccine formulations showed relatively lower levels of antibody responses. Thus, a vaccine formulation containing inactivated IBHV with PCEP or a mixture of PCEP and ABD2 (with a reduced dosage of PCEP) as an adjuvant may serve as a potential vaccine candidate. However, in order to overcome the risks associated with whole virus inactivated vaccines, characterization of additional viral capsid proteins, including fiber protein and penton of IBHV along with hexon protein in combination with more new generation adjuvants, will be helpful in further improvements of vaccines against IBHV infection.
Bhowmick, Sudipta; Ravindran, Rajesh; Ali, Nahid
Visceral leishmaniasis caused by the protozoan parasite Leishmania donovani complex is a potentially fatal disease if left untreated. Few treatment options exist and are toxic, costly and ineffective against resistant strains. Thus a safe and efficacious vaccine to combat this disease is needed. Previously, we reported that intraperitoneal administration of leishmanial antigens (LAg) entrapped in liposomes conferred protection to BALB/c mice against L. donovani challenge infection. However, this vaccine failed to protect mice when administered subcutaneously. We therefore evaluated whether formulation of LAg in combination with two commonly used human-compatible adjuvants, alum and saponin, could improve the protective efficacy of subcutaneously administered LAg, to a level comparable to that of the intraperitoneal liposomal vaccination. Vaccine formulations of LAg with alum or saponin failed to reduce parasite burden in the liver, and alum + LAg immunized mice also failed to reduce parasite burden in the spleen. Interestingly, saponin + LAg vaccination actually resulted in an increased L. donovani parasitic load in the spleen following L. donovani challenge, suggesting this regimen exacerbates the infection. In contrast, mice immunized intraperitoneally with Lip + LAg demonstrated significant protection in both liver and spleen, as expected. Mechanistically, we found that failure of alum + LAg to protect mice was associated with elevated levels of IL-4, whereas both IL-4 and IL-10 levels were increased in saponin + LAg immunized mice. This outcome served to exacerbate L. donovani infection in the saponin + LAg group, despite a concurrent increase in proinflammatory IFN-γ production. On the contrary, protection against L. donovani challenge in Lip + LAg immunized mice was associated with elevated levels of IFN-γ in conjunction with low levels of IL-4 and IL-10 production. These findings indicate that elevated levels of IL-4 may contribute to LAg vaccine failure
Aykanat, Verna; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond; Yap, Sharon; Rolan, Paul
AIM This study compared the responses between patients with unilateral sciatica and pain-free volunteers following administration of intradermal capsaicin. METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers received one injection per hour over 4 h of 1 µg and 10 µg capsaicin, into each calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm2) and the sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre-injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS Sciatica subjects experienced higher spontaneous pain and hyperalgesia responses in both legs compared with pain-free volunteers. The largest mean difference in spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg following 10 µg. The largest mean difference in hyperalgesia was 19.7 cm (95% CI 12.4, 27.0) at 60 min in the unaffected leg following 10 µg. Allodynia was greater in patients than in controls with the largest mean difference of 2.9 cm (95% CI 1, 4.8) at 5 min following 10 µg in the affected leg. Allodynia was also higher in the affected leg compared with the unaffected leg in sciatica patients with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following 10 µg. CONCLUSIONS The responses to intradermal capsaicin are quantitatively and qualitatively different in unilateral sciatica patients compared with pain-free controls. PMID:21740458
Chettri, Jiwan Kumar; Deshmukh, Sidhartha; Holten-Andersen, Lars
Numerous outbreaks of enteric red mouth disease (ERM) caused by Yersinia ruckeri O1 biotype 2 in rainbow trout farms are currently being recorded despite established vaccination procedures against this disease. This could indicate that the currently used application of single immersion vaccination...
Yen, Chia-Feng; Lin, Jin-Ding
The study aims to determine hepatitis B vaccination coverage rates among community-dwelling teenagers with an intellectual disability in Taiwan and to identify the possible influencing factors of their vaccination. The present paper was part of the results of the "2007 National Survey on Healthy Behaviors and Preventive Health Utilizations of…
Jo, Youn Yi; Lee, Mi Geum; Yun, Soon Young; Lee, Kyung Cheon
Intradermal injections of indigo carmine for sentinel node mapping are considered safe and no report of an adverse reaction has been published. The authors described two cases of profound hypotension in women that underwent breast-conserving surgery after an intradermal injection of indigo carmine into the periareolar area for sentinel node mapping.
Jo, Youn Yi; Lee, Mi Geum; Yun, Soon Young; Lee, Kyung Cheon
Intradermal injections of indigo carmine for sentinel node mapping are considered safe and no report of an adverse reaction has been published. The authors described two cases of profound hypotension in women that underwent breast-conserving surgery after an intradermal injection of indigo carmine into the periareolar area for sentinel node mapping.
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
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.
Reyburn, Rita; Nand, Devina; Nguyen, Cattram; Naidu, Shivnay; Bali, Arishma; Rokovutoro, Miriama; Ratu, Tupou; Kumar, Simon; Lewis, Donald; Smith, Varanisese; Russell, Fiona
Post-licensure studies to evaluate vaccine impact are an important component of introducing new vaccines. Such studies often rely on routinely collected data but the limitations to these data must be understood. To validate administrative data for use in 10-valent pneumococcal conjugate and rotavirus vaccine impact evaluations we have audited the two electronic database capturing hospital admissions in Fiji for completeness and consistency. Hospital admission data for one week per year between 2007-2011 and 2014-2015 was collected from ward registers for selected hospitals. Ward registers were defined as the reference standard and compared to data captured in electronic databases. Data quality was assessed for completeness of admissions data (percentage of admissions in the electronic database, expressed as sensitivity), consistency of complete reporting (determined by identifying variables associated to complete reporting), and completeness of coding (percentage of admissions in the electronic database with an assigned ICD-10-AM code). Over all hospitals and years, the sensitivity for completeness of admission data was 83% (95% CI: 81.3, 84.6). Consistency of complete reporting varied and was highest at tertiary hospitals using the electronic database (sensitivity: 89.1%, 95% CI: 87.4, 90.7). The overall completeness of coding at tertiary hospitals was 90.8% (95% CI: 90.5, 91.1) with annual and hospital variation. The administrative data in the electronic databases in Fiji are of reasonable quality for the vaccine impact evaluation. This quantification of the missing data can be used to adjust the vaccine impact estimates. Copyright © 2017 Elsevier Ltd. All rights reserved.
Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C
Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.
Andrea L H Arnett
Full Text Available Recombinant adeno-associated viral (rAAV vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV. rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV-vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, one month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice.
Chen, Hui; Gao, Na; Fan, Dongying; Wu, Jiangman; Zhu, Junping; Li, Jieqiong; Wang, Juan; Chen, Yanlei; An, Jing
As a potential cytokine adjuvant of DNA vaccines, granulocyte-macrophage colony–stimulating factor (GM-CSF) has received considerable attention due to its essential role in the recruitment of antigen-presenting cells, differentiation and maturation of dendritic cells. However, in our recent study of a Japanese encephalitis virus (JEV) DNA vaccine, co-inoculation of a GM-CSF plasmid dramatically suppressed the specific IgG response and resulted in decreased protection against JEV challenge. It is known that GM-CSF has been used in clinic to treat neutropenia for repopulating myeloid cells, and as an adjuvant in vaccine studies; it has shown various effects on the immune response. Therefore, in this study, we characterized the suppressive effects on the immune response to a JEV DNA vaccine by the co-administration of the GM-CSF-expressing plasmid and clarified the underlying mechanisms of the suppression in mice. Our results demonstrated that co-immunization with GM-CSF caused a substantial dampening of the vaccine-induced antibody responses. The suppressive effect was dose- and timing-dependent and likely related to the immunogenicity of the antigen. The suppression was associated with the induction of immature dendritic cells and the expansion of regulatory T cells but not myeloid-derived suppressor cells. Collectively, our findings not only provide valuable information for the application of GM-CSF in clinic and using as a vaccine adjuvant but also offer further insight into the understanding of the complex roles of GM-CSF. PMID:22493704
Pinson, Michelle L; Waibel, Kirk H
Immunoglobulin (Ig) E antibodies to galactose-α-1,3-galactose (α-Gal) are associated with delayed anaphylaxis to mammalian food products and gelatin-based foods (Commins et al., J Allergy Clin Immunol 2009;123:426; Caponetto et al., J Allergy Clin Immunol Pract 2013;1:302). We describe a patient with α-Gal allergy who successfully tolerated the live zoster vaccine and we review anaphylactic reactions reported to this vaccine. Our patient, who tolerated a vaccine containing the highest gelatin content, is reassuring but continued safety assessment of gelatin-containing vaccines for this patient cohort is recommended as there are multiple factors for this patient cohort that influence the reaction risk. Published by Elsevier Ltd.
Full Text Available Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5 expressing three proteins (E7, E6, and E5 of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose induced a strong activation of E7-specific interferon-γ (INF-γ-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.
... HUMAN SERVICES Health Resources and Services Administration National Vaccine Injury Compensation Program: Addition to the Vaccine Injury Table to Include All Vaccines Against Seasonal Influenza AGENCY: Health... vaccines against seasonal influenza are covered under the National Vaccine Injury Compensation Program...
Silva Célio L
Full Text Available Abstract Background The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB. Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally. Results We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65 or complexed (COMP-hsp65, and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 μg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-γ and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 μg. Conclusion Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this
Ortiz de Lejarazu, Raúl; Tamames, Sonia
Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Schmidt, Signe Tandrup; Khadke, Swapnil; Korsholm, Karen Smith
A prerequisite for vaccine-mediated induction of CD8(+) T-cell responses is the targeting of dendritic cell (DC) subsets specifically capable of cross-presenting antigen epitopes to CD8(+) T cells. Administration of a number of cationic adjuvants via the intraperitoneal (i.p.) route has been shown...... to result in strong CD8(+) T-cell responses, whereas immunization via e.g. the intramuscular (i.m.) or subcutaneous (s.c.) routes often stimulate weak CD8(+) T-cell responses. The hypothesis for this is that self-drainage of the adjuvant/antigen to the lymphoid organs, which takes place upon i.p...... with polyinosinic:polycytidylic acid electrostatically adsorbed to the surface. Biodistribution studies with radiolabeled CAF09 and a surface-adsorbed model antigen [ovalbumin (OVA)] showed that a significantly larger fraction of the vaccine dose localized in the draining lymph nodes (dLNs) and the spleen 6h after...
Chung, Eun Hee
Currently, the increasing numbers of vaccine administrations are associated with increased reports of adverse vaccine reactions. Whilst the general adverse reactions including allergic reactions caused by the vaccine itself or the vaccine components, are rare, they can in some circumstances be serious and even fatal. In accordance with many IgE-mediated reactions and immediate-type allergic reactions, the primary allergens are proteins. The proteins most often implicated in vaccine allergies are egg and gelatin, with perhaps rare reactions to yeast or latex. Numerous studies have demonstrated that the injectable influenza vaccine can be safely administered, although with appropriate precautions, to patients with severe egg allergy, as the current influenza vaccines contain small trace amounts of egg protein. If an allergy is suspected, an accurate examination followed by algorithms is vital for correct diagnosis, treatment and decision regarding re-vaccination in patients with immediate-type reactions to vaccines. Facilities and health care professionals should be available to treat immediate hypersensitivity reactions (anaphylaxis) in all settings where vaccines are administered.
Cichocka-Jarosz, Ewa; Stobiecki, Marcin; Brzyski, Piotr; Rogatko, Iwona; Nittner-Marszalska, Marita; Sztefko, Krystyna; Czarnobilska, Ewa; Lis, Grzegorz; Nowak-Węgrzyn, Anna
The direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age. To determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications. We reviewed the medical records of 91 children and 121 adults. Bee venom allergy was exposure dependent, regardless of age (P venom allergic group, specific IgE levels were significantly higher in children (29.5 kUA/L; interquartile range, 11.30-66.30 kUA/L) compared with adults (5.10 kUA/L; interquartile range, 2.03-8.30 kUA/L) (P venom were higher in bee venom allergic children compared with the wasp venom allergic children (P venom. At concentrations lower than 0.1 μg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049). The basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Evaluating the most effective distribution strategies to assure administration of pandemic H1N1 influenza vaccine to New York State children and adolescents: evaluation using the New York State Immunization Information System.
Bednarczyk, Robert A; DuVall, Sarah; Meldrum, Megan D; Flynn, Michael K; Santilli, Loretta A; Easton, Delia E; Sharma, Priya; Blog, Debra S; Zansky, Shelley M; McNutt, Louise-Anne; Birkhead, Guthrie S
To examine differences in H1N1 influenza vaccine distribution strategies that may impact the ability to rapidly administer vaccine during a pandemic or public health emergency. Retrospective evaluation of immunization data in the New York State Immunization Information System (NYSIIS). Analysis of existing NYSIIS data. Children and adolescents younger than 19 years for whom information on at least 1 H1N1 influenza vaccine was present in NYSIIS. Median time to administer vaccines to children and adolescents younger than 19 years by December 31, 2009, by county; venue of H1N1 vaccine administration (local health department [LHD] or private medical provider); comparison of immunization-seeking behavior for routine childhood vaccinations and H1N1 vaccine. A total of 459 189 first or only doses of H1N1 influenza vaccine were recorded in NYSIIS as being administered to New York State, outside of New York City, children aged less than 19 years, between October 2, 2009, and December 31, 2009. Overall, LHD administered 31% of H1N1 vaccine doses; in counties having population less than 100,000, LHD administered 63% of H1N1 doses compared with 23% in counties having population more than 100,000. Time to median administration was faster for LHD in smaller counties and similar for LHD and private medical providers in larger counties. Children who always received routine childhood immunizations either within or outside of their county of residence often had the same practice for H1N1 vaccine, with 85% of children following these patterns. Children who did not follow these patterns were more likely to receive H1N1 influenza vaccine through LHD. Local health departments were able to rapidly administer large quantities of H1N1 influenza vaccine, and patterns of health care seeking relying on increased use of LHD needs to be further studied for future public health emergency planning.
Full Text Available Vaccination against tuberculosis (TB is prohibited in cattle or other species subjected to specific TB eradication campaigns, due to the interference that it may cause with the official diagnostic tests. However, immunization with a heat-inactivated (HI Mycobacterium bovis vaccine via the oral route has been suggested to overcome this issue. In this study, the main goal was to assess the interference of the HI vaccine by different routes of administration using a previous vaccination and re-vaccination (boosting protocol. TB-free kid goats were divided into three groups: oral (n = 16, intramuscular (IM; n = 16, and control (n = 16. Results showed that there was a significant difference in the percentage of animals positive to the single intradermal test (SIT and blood based interferon-gamma release assay (IGRA caused by vaccination when performed in the IM group compared to the oral group (p < 0.001. Nevertheless, no positivity to the SIT or IGRA test was observed in orally vaccinated goats regardless of the different interpretation criteria applied. None of the groups presented positive antibody titers using an in-house ELISA and samples collected 2 months after the boost. These results suggest the potential usefulness of the HI vaccine by the oral route in goats to minimize the interference on diagnostic tests (skin and IGRA tests and reducing the necessity of defined antigens to replace the traditional purified protein derivatives for diagnosis. Finally, the results pave the way to future efficacy studies in goats using different routes of HI vaccination.
Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route.
Ravindran, Rajesh; Maji, Mithun; Ali, Nahid
The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human administration. Herein, we therefore evaluated the immune response and protection induced by liposomal soluble leishmanial antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM elicited partial protection against experimental visceral leishmaniasis. In contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly higher levels of protection in liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection conferred by this formulation was sustained up to 12 weeks of immunization, and infection was controlled for at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ production also by CD8⁺ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine formulation for the induction of durable protection against L. donovani through a human administrable route.
Full Text Available Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that protective levels of antibodies to hemagglutinin were induced after two immunizations of modified non-replicating mRNA encoding influenza H10 encapsulated in lipid nanoparticles (LNP in non-human primates. While both intradermal (ID and intramuscular (IM administration induced protective titers, ID delivery generated this response more rapidly. Circulating H10-specific memory B cells expanded after each immunization, along with a transient appearance of plasmablasts. The memory B cell pool waned over time but remained detectable throughout the 25-week study. Following prime immunization, H10-specific plasma cells were found in the bone marrow and persisted over time. Germinal centers were formed in vaccine-draining lymph nodes along with an increase in circulating H10-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells, a population shown to correlate with high avidity antibody responses after seasonal influenza vaccination in humans. Collectively, this study demonstrates that mRNA/LNP vaccines potently induce an immunological repertoire associated with the generation of high magnitude and quality antibodies.
Hampson, Katie; Cleaveland, Sarah; Briggs, Deborah
Background Prompt post-exposure prophylaxis (PEP) is essential in preventing the fatal onset of disease in persons exposed to rabies. Unfortunately, life-saving rabies vaccines and biologicals are often neither accessible nor affordable, particularly to the poorest sectors of society who are most at risk and upon whom the largest burden of rabies falls. Increasing accessibility, reducing costs and preventing delays in delivery of PEP should therefore be prioritized. Methodology/Principal Findings We analyzed different PEP vaccination regimens and evaluated their relative costs and benefits to bite victims and healthcare providers. We found PEP vaccination to be an extremely cost-effective intervention (from $200 to less than $60/death averted). Switching from intramuscular (IM) administration of PEP to equally efficacious intradermal (ID) regimens was shown to result in significant savings in the volume of vaccine required to treat the same number of patients, which could mitigate vaccine shortages, and would dramatically reduce the costs of implementing PEP. We present financing mechanisms that would make PEP more affordable and accessible, could help subsidize the cost for those most in need, and could even support new and existing rabies control and prevention programs. Conclusions/Significance We conclude that a universal switch to ID delivery would improve the affordability and accessibility of PEP for bite victims, leading to a likely reduction in human rabies deaths, as well as being economical for healthcare providers. PMID:21408121
Standaert, Baudouin; Van de Mieroop, Els; Nelen, Vera
Rotavirus vaccination has been reimbursed in Belgium since November 2006 with a high uptake (>85%). Economic analyses of the vaccine have been reported, including estimates of indirect cost gain related to the reduction in work absenteeism. The objective of this study was to evaluate the latter parameter using real-life data. A simple model estimated the reduction in absent workdays per working mother with a firstborn baby after the introduction of the rotavirus vaccine. Next, data on work absences were retrospectively analysed (from 2003 to 2012) using a database of administrative employees (n=11,600 working women per year) in the City of Antwerp. Observed reductions in absenteeism after the introduction of the vaccine were compared with the results from the model. These reductions would most likely be observed during the epidemic periods of rotavirus (from January to the end of May) for short-duration absences of ≤ 5 days. We compared data from outside epidemic periods (from June to December), expecting no changes over time prevaccine and postvaccine introduction, as well as with a control group of women aged 30-35 years with no first child. Model estimates were 0.73 working days gained per working mother. In the database of the City of Antwerp, we identified a gain of 0.88 working days during the epidemic period, and an accumulated gain of 2.24 days over a 3-year follow-up period. In the control group, no decrease in absenteeism was measured. Giving vaccine access to working mothers resulted in an estimated accumulated net cost gain of €187 per mother. Reduction in absenteeism among working mothers was observed during periods of the epidemic after the introduction of the rotavirus vaccine in Belgium. This reduction is in line with estimates of indirect cost gains used in economic evaluations of the rotavirus vaccine. HO-12-12768. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Selleri, Paolo; Di Girolamo, Nicola; Vögtlin, Andrea; Fileccia, Ivan; Hoop, Richard; Bongiovanni, Laura
A novel bivalent vaccine to protect against myxomatosis and rabbit haemorrhagic disease is commercially available for pet rabbits. To describe the appearance of cutaneous lesions arising in pet rabbits positive for myxoma virus (MV) by RT-PCR evaluation shortly after vaccination. Four pet rabbits presenting with papular, crusting skin lesions ~10 days after vaccination. Histological evaluation of formalin-fixed skin biopsies obtained from lesional skin (case 1). Real-time polymerase chain reaction (RT-PCR) evaluation of paraffin-embedded tissue from skin biopsies (case 1) and crusts obtained from the lesion surface (cases 2-4) for myxoma virus are reported as cycle threshold (Ct ) values. Lesions affecting the ear pinna, dorsal aspect of the nose, vulva and/or conjunctiva are reported. Histopathological findings included severe ulcerative, necrotizing dermatitis and intralesional cytoplasmic inclusion bodies in myxoma cells. DNA was amplified from all the paraffin-embedded skin biopsies (Ct = 34-35) and crusts (Ct = 20-24). Although a wild virus challenge cannot be definitively excluded, veterinarians and pet-owners should be aware that cutaneous lesions have been observed after vaccination with this novel vaccine in low numbers of rabbits. © 2014 ESVD and ACVD.
Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine
Full Text Available Abstract Background Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α and chicken interleukin-18 (chIL-18 as natural immunomodulators. Results Oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens. Conclusions Our results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2.
Full Text Available Rotavirus is the leading cause of severe diarrheal disease among newborns. Plant-based rotavirus vaccines have been developed in recent years and have been proven to be effective in animal models. In the present study, we report a bivalent vaccine candidate expressing rotavirus subunits VP6 and NSP4 fused with the adjuvant subunit B of E. coli heat-labile enterotoxin (LTB in maize seeds. The RT-PCR and Western blot results showed that VP6 and LTB-NSP4 antigens were expressed and accumulated in maize seeds. The expression levels were as high as 0.35 and 0.20% of the total soluble protein for VP6 and LTB-NSP4, respectively. Oral administration of transgenic maize seeds successfully stimulated systemic and mucosal responses, with high titers of serum IgG and mucosal IgA antibodies, even after long-term storage. This study is the first to use maize seeds as efficient generators for the development of a bivalent vaccine against rotavirus.
Feng, Hao; Li, Xin; Song, Weibin; Duan, Mei; Chen, Hong; Wang, Tao; Dong, Jiangli
Rotavirus is the leading cause of severe diarrheal disease among newborns. Plant-based rotavirus vaccines have been developed in recent years and have been proven to be effective in animal models. In the present study, we report a bivalent vaccine candidate expressing rotavirus subunits VP6 and NSP4 fused with the adjuvant subunit B of E. coli heat-labile enterotoxin (LTB) in maize seeds. The RT-PCR and Western blot results showed that VP6 and LTB-NSP4 antigens were expressed and accumulated in maize seeds. The expression levels were as high as 0.35 and 0.20% of the total soluble protein for VP6 and LTB-NSP4, respectively. Oral administration of transgenic maize seeds successfully stimulated systemic and mucosal responses, with high titers of serum IgG and mucosal IgA antibodies, even after long-term storage. This study is the first to use maize seeds as efficient generators for the development of a bivalent vaccine against rotavirus. PMID:28620404
van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W; Daemen, Toos
The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo
Kim, Eun; Erdos, Geza; Huang, Shaohua; Kenniston, Thomas; Falo Jr, Louis D.; Gambotto, Andrea
Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barr? syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally ...
Starr, S Paul
A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.
Quaternized chitosan nanoparticles loaded with the combined attenuated live vaccine against Newcastle disease and infectious bronchitis elicit immune response in chicken after intranasal administration.
Zhao, Kai; Li, Shanshan; Li, Wei; Yu, Lu; Duan, Xutong; Han, Jinyu; Wang, Xiaohua; Jin, Zheng
Newcastle disease (ND) and infectious bronchitis (IB) are important diseases, which cause respiratory diseases in chickens, resulting in severely economic losses in the poultry industry. In this study, N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMC) were synthesized as adjuvant and delivery carrier for vaccine antigens. N-2-HACC-CMC/NDV/IBV nanoparticles (NPs) (NDV/La Sota and IBV/H120 encapsulated in N-2-HACC-CMC NPs) and N-2-HACC-CMC/NDV-IBV NPs (the mixing of N-2-HACC-CMC/NDV NPs and N-2-HACC-CMC/IBV NPs in a ratio of 1:1) were prepared by the polyelectrolyte composite method, respectively. Both nanoparticles exhibited lower cytotoxicity and higher stability. Their bioactivities were maintained when they were stored at 37 °C for three weeks. Release assay in vitro showed that both NDV and IBV could be sustainably released from the nanoparticles after an initial burst release. In vivo immunization of chickens showed that N-2-HACC-CMC/NDV/IBV NPs or N-2-HACC-CMC/NDV-IBV NPs intranasally induced higher titers of IgG and IgA antibodies, significantly promoted proliferation of lymphocytes and induced higher levels of interleukine-2 (IL-2), IL-4 and interferon-γ (IFN-γ) than the commercially combined attenuated live vaccine did. This is the first study in the field of animal vaccines demonstrating that intranasal administration of chickens with antigens (NDV and IBV) encapsulated with chitosan derivative could induce humoral, cellular, and mucosal immune responses, which protected chickens from the infection of highly virulent NDV and IBV. This study indicated that N-2-HACC-CMC could be used as an efficient adjuvant and delivery carrier for further development of mucosal vaccines and drugs and could have an immense application potential in medicine.
Carrade, Danielle D; Affolter, Verena K; Outerbridge, Catherine A; Watson, Johanna L; Galuppo, Larry D; Buerchler, Sabine; Kumar, Vijay; Walker, Naomi J; Borjesson, Dori L
BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the same series of 12 injections, 3-4 weeks later, at another site. Wheals were measured and palpated at 0.25, 4, 24, 48, 72 h and 7 days post-injection. Biopsies were obtained at 48 and 72 h and 7 days post-injection. Mixed leukocyte reactions were performed 1 week prior to the first injections and 3 weeks after the second injections. RESULTS. There were no adverse local or systemic responses to two intradermal injections of allogeneic MSC. MSC injection resulted in minor wheal formation, characterized by mild dermatitis, dermal edema and endothelial hyperplasia, that fully resolved by 48-72 h. No differences were noted between allogeneic and autologous MSC. The second injection of MSC did not elicit more significant physical or histomorphologic alterations compared with the first MSC injection. Neither allogeneic nor autologous UCT-derived MSC stimulated or suppressed baseline T-cell proliferation in vitro prior to or after two MSC administrations. CONCLUSIONS. Equine allogeneic UCT MSC may be safely administered intradermally on multiple occasions without eliciting a measurable cellular immune response.
Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-α.
Rahman, Md Masudur; Uyangaa, Erdenebelig; Han, Young Woo; Hur, Jin; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug
Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to limitations in the efficacy against currently circulating ND viruses, existing vaccination strategies require improvements, and incorporating immunomodulatory cytokines with existing vaccines might be a novel approach. Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interferon-α (chIFN-α) using attenuated Salmonella enterica serovar Typhimurium on an inactivated ND vaccine. Our results demonstrate that oral administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α provided enhanced systemic and mucosal immune responses, as determined by serum hemagglutination inhibition antibody and NDV Ag-specific IgG as well as NDV Ag-specific IgA in lung and duodenal lavages of chickens immunized with inactivated ND vaccine via the intramuscular or intranasal route. Notably, combined oral administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α significantly enhanced systemic and mucosal immunity in ND-vaccinated chickens, compared to single administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α. In addition, oral co-administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α provided enhanced NDV Ag-specific proliferation of peripheral blood mononuclear cells and Th1-biased cell-mediated immunity, compared to single administration of either construct. Therefore, our results provide valuable insight into the modulation of systemic and mucosal immunity by incorporation of immunomodulatory chIL-18 and chIFN-α using Salmonella vaccines into existing ND vaccines.
Sylwia, Malinowska; Krzysztof, Mlosek Robert
Cellulite affects the majority of women and is an unacceptable cosmetic defect. Therefore, effective methods for cellulite reduction are being sought. Intradermal mesotherapy is one of such methods. The aim of the study was to assess the efficacy of intradermal mesotherapy in cellulite reduction, using conventional and high-frequency ultrasound. Twenty-one women with cellulite underwent a series of intradermal mesotherapy procedures. The following parameters were assessed: thickness of epidermis, dermis and hypodermis, echogenicity of dermis and the surface area of serrated hypodermis-dermis junction. Furthermore, the thigh circumference was measured; body mass index and cellulite severity were assessed based on photographs using Nürnberger-Müller's scale. Intradermal mesotherapy reduced severity of cellulite. The surface area of serrated hypodermis-dermis junction and hypodermis thickness decreased significantly as compared to baseline. Cellulite reduction was also confirmed by palpation, decreased thigh circumference and the Nürnberger-Müller's grade. There were no statistically significant changes in epidermis or dermis thickness, body weight and the BMI. Intradermal mesotherapy offers effective cellulite reduction. It is a simple and safe treatment, which makes it popular. Further research in mesotherapy is essential due to a limited number of published studies. Ultrasound is a useful method to monitor intradermal mesotherapy and assess its efficacy.
Gadroen, Kartini; Straus, Sabine M J M; Pacurariu, Alexandra; Weibel, Daniel; Kurz, Xavier; Sturkenboom, Miriam C J M
This study aims to describe the frequency and quality of spontaneous narcolepsy case reports following administration of pandemic influenza vaccine as captured in the Eudravigilance database. We conducted a retrospective descriptive study of spontaneous Individual Case Safety Reports (ICSRs), reporting narcolepsy following administration of pandemic influenza vaccine as received by Eudravigilance until July 2014. De-duplication was carried out by Eudravigilance. Frequency of reporting is described as number of ICSRs received per month over time. The quality of the ICSRs was evaluated by completeness of information and diagnostic certainty using the Automated Brighton Collaboration case definition tool (ABC-tool) for narcolepsy. After de-duplication, a total of 1333 ICSRs of narcolepsy and/or cataplexy following pandemic influenza vaccine were identified, originating from 18 countries worldwide. Most of the ICSRs (61.9%) originated from the signaling countries, Sweden and Finland. Although de-duplication of case reports was carried out, it is suspected that many duplicates exist, in particular from Sweden. The majority of the ICSRs (95.3%), reported exposure to Pandemrix®. Only few reports were received for Arepanrix® (1.6%) or Focetria® (0.5%), and Celvapan® (0.1%). Of those ICSRs reporting age, 73.1% concerned persons below age of 20years. When using the ABC-tool, all ICSRs were classified as having insufficient information to meet the Brighton Collaboration case definition of narcolepsy. An increase in reporting of narcolepsy appeared in Eudravigilance only after awareness was raised by the national authorities. Most narcolepsy reports were received from countries where the signal initially occurred, and were related to Pandemrix® in children/adolescents. Basic information about the patient and the exposure was present in most of the ICSRs. The ICSRs captured by Eudravigilance however, do not collect enough information to assess the diagnostic certainty
Elizabeth A. Thoryk
Full Text Available A vast body of evidence suggests that nanoparticles function as potent immune-modulatory agents. We have previously shown that Merck proprietary Lipid NanoParticles (LNPs markedly boost B-cell and T-cell responses to sub-unit vaccine antigens in mice. To further evaluate the specifics of vaccine delivery and dosing regimens in vivo, we performed immunogenicity studies in BALB/c and C57BL/6 mice using two model antigens, Hepatitis B Surface Antigen (HBsAg and Ovalbumin (OVA, respectively. To assess the requirement for co-administration of antigen and LNP for the elicitation of immune responses, we evaluated immune responses after administering antigen and LNP to separate limbs, or administering antigen and LNP to the same limb but separated by 24 h. We also evaluated formulations combining antigen, LNP, and aluminum-based adjuvant amorphous aluminum hydroxylphosphate sulfate (MAA to look for synergistic adjuvant effects. Analyses of antigen-specific B-cell and T-cell responses from immunized mice revealed that the LNPs and antigens must be co-administered—both at the same time and in the same location—in order to boost antigen-specific immune responses. Mixing of antigen with MAA prior to formulation with LNP did not impact the generation of antigen-specific B-cell responses, but drastically reduced the ability of LNPs to boost antigen-specific T-cell responses. Overall, our data demonstrate that the administration of LNPs and vaccine antigen together enables their immune-stimulatory properties.
Hein-Kristensen, L; Jørgensen, M J; Ravn, H
The World Health Organisation recommends vitamin A supplementation (VAS) to children aged 6 months to 5 years in low-income countries, and for logistic reasons, this has been linked to routine childhood immunizations. Observational studies suggest that VAS given with diphtheria-tetanus-pertussis ......The World Health Organisation recommends vitamin A supplementation (VAS) to children aged 6 months to 5 years in low-income countries, and for logistic reasons, this has been linked to routine childhood immunizations. Observational studies suggest that VAS given with diphtheria......-tetanus-pertussis (DTP) vaccine may increase mortality from non-targeted diseases. We investigated the non-targeted effect of pretreatment with VAS and DTP vaccine in a murine model of experimental cerebral malaria. Our a priori hypothesis was that VAS/DTP would aggravate the infection. We found that the effect of VAS...
Jadhav Suresh S
Full Text Available Abstract Background Measles was responsible for an estimated 100,000 deaths worldwide in 2008. Despite being a vaccine-preventable disease, measles remains a major cause of morbidity and mortality in young children. Although a safe and effective injectable measles vaccine has been available for over 50 years it has not been possible to achieve the uniformly high levels of coverage (required to achieve measles eradication in most parts of the developing world. Aerosolised measles vaccines are now under development with the hope of challenging the delivery factors currently limiting the coverage of the existing vaccine. Methods We used a modified CHNRI methodology for setting priorities in health research investments to assess the strengths and weaknesses of this emerging intervention to decrease the burden of childhood pneumonia. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging aerosol vaccines against measles relevant to several criteria of interest. Although there are a number of different aerosol vaccine approaches under development, for the purpose of this exercise, all were considered as one intervention. The criteria of interest were: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each
Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-?
Rahman, Md. Masudur; UYANGAA, Erdenebelig; Han, Young Woo; Hur, Jin; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; EO, Seong Kug
Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to limitations in the efficacy against currently circulating ND viruses, existing vaccination strategies require improvements, and incorporating immunomodulatory cytokines with existing vaccines might be a novel approach. Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interfero...
Chettri, Jiwan Kumar
significant losses in aquacultural enterprises but vaccination methods implemented since the 1990s have demonstrated their role as one of the most efficient disease control strategies. These have been particularly successful with regard to bacterial diseases in Norwegian salmon farming where multivalent...... 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...
Full Text Available We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old and adult (7 weeks old BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.
Morgan, Erin E; Miller, William H; Wagner, Bettina
Skin hypersensitivities (allergies) in horses are often diagnosed using clinical signs only. Intradermal testing or serological assays are diagnostic options to confirm the allergic nature of the disease and to identify the allergen(s). Our objective was to develop an allergen-specific enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody specific for horse IgE and to examine its potential for allergen detection in serum in comparison to intradermal testing. Intradermal testing with 61 allergen extracts was performed on 10 horses affected with skin hypersensitivity. Their sera were analyzed by ELISA for IgE antibodies to the same allergens. The kappa test of concordance was used for comparison of the results of both tests. Out of 61 allergen extracts, only two (Timothy and Quack) had kappa values greater than 0.60, suggesting a substantial agreement between skin testing and IgE ELISA. The statistical comparison of the remaining 59 allergens showed little or no concordance between the tests beyond chance. To identify parameters that may influence the sensitivity of the ELISA, the assay was modified to detect allergen-specific IgGb and IgG(T) in serum, and the protein content in all allergen extracts was determined by SDS-PAGE. The commercial allergen extracts revealed a high variation in detectable protein. High concentrations of allergen-specific IgG in horse serum were found to compete with IgE for binding to the plates. In conclusion, an ELISA using whole serum and crude allergen preparations provides limited diagnostic information in horses. The reliable diagnosis of allergens in equine skin hypersensitivity is essential to improve allergen-specific treatments, such as hyposensitization, or the development of allergy vaccines.
DNA vaccines elicit durable protective immunity against individual or simultaneous 1 infections with Lassa and Ebola viruses in guinea pigs 2 3...previously developed optimized DNA vaccines against both Lassa fever and Ebola 15 hemorrhagic fever viruses and demonstrated that they were protective...with 50 µg of each DNA vaccine or a mock 18 vaccine at discrete sites by intradermal electroporation. Five weeks following the 19 second
Shaw, C A; Li, Y; Tomljenovic, L
Our previous ecological studies of autism spectrum disorder (ASD) has demonstrated a correlation between increasing ASD rates and aluminium (Al) adjuvants in common use in paediatric vaccines in several Western countries. The correlation between ASD rate and Al adjuvant amounts appears to be dose-dependent and satisfies 8 of 9 Hill criteria for causality. We have now sought to provide an animal model to explore potential behavioural phenotypes and central nervous system (CNS) alterations using s.c. injections of Al hydroxide in early postnatal CD-1 mice of both sexes. Injections of a "high" and "low" Al adjuvant levels were designed to correlate to either the U.S. or Scandinavian paediatric vaccine schedules vs. control saline-injected mice. Both male and female mice in the "high Al" group showed significant weight gains following treatment up to sacrifice at 6 months of age. Male mice in the "high Al" group showed significant changes in light-dark box tests and in various measures of behaviour in an open field. Female mice showed significant changes in the light-dark box at both doses, but no significant changes in open field behaviours. These current data implicate Al injected in early postnatal life in some CNS alterations that may be relevant for a better understanding of the aetiology of ASD. © 2013.
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.
Grissett, Gretchen P; White, Brad J; Anderson, David E; Larson, Robert E; Miesner, Matt D
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.
Liu, Jixiao; Feng, Keke; Zhao, Lu; Luo, Haining; Zhu, Yingjun
The efficacy of DNA vaccines may be improved by small interfering (si)RNA adjuvants targeting pro-apoptotic genes. The aim of the present study was to investigate the capacity of siRNAs targeting B-cell lymphoma 2 homologous antagonist killer (BAK) and B-cell lymphoma 2-associated X protein (BAX) to improve the efficacy of a cytomegalovirus (CMV) vaccine. BALB/c mice were divided into four groups (n=18 in each): unimmunized and immunized with pcDNA 3.1-pp65 expressing CMV 65 kDa matrix phosphoprotein and BAK + BAX siRNAs, pcDNA 3.1-pp65 and control siRNA, or control pcDNA 3.1 and BAK + BAX siRNAs. Immunizations were performed twice with an interval of 3 weeks. CMV-specific mouse splenocyte interferon (IFN)-γ secretion was assessed by ELISPOT; furthermore, an in vivo cytotoxic T lymphocyte assay was performed 2 weeks after the last immunization. After lethal CMV challenge of the mice, body weight, virus titers in the spleens and salivary glands as well as survival were recorded. The amount of splenocytes secreting IFN-γ in response to CMV pp65 peptides and specific lysis of peptide-pulsed target cells were significantly higher in mice administered pcDNA3.1-pp65 and BAK + BAX siRNAs than those in mice administered pcDNA3.1-pp65 and control siRNA (PsiRNAs were significantly lower than those in mice immunized with pcDNA3.1-pp65 and control siRNA (PsiRNA or BAK + BAX siRNAs survived for longer, and at 21 days after lethal CMV challenge, 66 and 100% of these mice survived, respectively. These mice also experienced less weight loss compared with mice immunized with pcDNA3.1-pp65 and control siRNA (PsiRNAs targeting BAK and BAX improved the efficacy of CMV pp65 DNA vaccine.
Beirne, Paul V; Hennessy, Sarah; Cadogan, Sharon L; Shiely, Frances; Fitzgerald, Tony; MacLeod, Fiona
Hypodermic needles of different sizes (gauges and lengths) can be used for vaccination procedures. The gauge (G) refers to the outside diameter of the needle tubing. The higher the gauge number, the smaller diameter of the needle (eg a 25 G needle is 0.5 mm in diameter and is narrower than a 23 G needle (0.6 mm)). Many vaccines are recommended for injection into muscle (intramuscularly), although some are delivered subcutaneously (under the skin) and intradermally (into skin). Choosing an appropriate length and gauge of a needle may be important to ensure that a vaccine is delivered to the appropriate site and produces the maximum immune response while causing the least possible harm. There are some conflicting guidelines regarding the lengths and gauges of needles that should be used for vaccination procedures in children and adolescents. To assess the effects of using needles of different lengths and gauges for administering vaccines to children and adolescents on vaccine immunogenicity (the ability of the vaccine to elicit an immune response), procedural pain, and other reactogenicity events (adverse events following vaccine administration). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 10), MEDLINE and MEDLINE in Progress via Ovid (1947 to November 2014), EMBASE via Ovid (1974 to November 2014), and CINAHL via EBSCOhost (1982 to November 2014). We also searched reference lists of articles and textbooks, the proceedings of vaccine conferences, and three clinical trial registers. Randomised controlled trials evaluating the effects of using hypodermic needles of any gauge or length to administer any type of vaccine to people aged from birth to 24 years. Three review authors independently extracted trial data and assessed the risk of bias. We contacted trial authors for additional information. We rated the quality of evidence using the GRADE system. We included five trials involving 1350 participants. Data for the
Roh, Ha-Jung; Jordan, Brian J; Hilt, Deborah A; Ard, Mary B; Jackwood, Mark W
studies in our laboratory showed that the Arkansas-Delmarva Poultry Industry (Ark-DPI) vaccine given to 1-day-old chickens by hatchery spray cabinet replicated poorly and failed to adequately protect broilers against homologous virus challenge, whereas the same vaccine given by eye-drop did replicate and the birds were protected following homologous virus challenge. To determine if mechanical damage following spray application plays a role in failure of the Ark-DPI vaccine, we examined the morphology of three Ark-DPI vaccines from different manufacturers using an electron microscope and included a Massachusetts (Mass) vaccine as control. One of the Ark-DPI vaccines (vaccine A) and the Mass vaccine had significantly (P hatchery spray cabinet, suggesting that some other factor is contributing to the failure of that vaccine when given by that method.
Joseba M Garrido
Full Text Available Although there is a wide consensus on the efficacy of paratuberculosis vaccination to limit economic losses, its use has been restricted because of its interference in the diagnosis of tuberculosis. Data from a vaccine clinical trial in the Basque Country (Spain has been evaluated in relationship with bovine tuberculosis intradermal test results. The trial included two herds applying a Test and Culling strategy and five applying an inactivated vaccine. The vaccine was applied to animals of all ages present in each vaccinated herd when joining the trial, and then to all the replacers within their first three months of life. Yearly testing done with the comparative intradermal test (CIT was applied to all animals older than 6 weeks. Between 2005 and 2011, the study generated 2,033 records from Vaccinated Herds (VH and 2,252 from Test and Cull herds (TC. Pre-vaccination positive results rate was 2.40% among the 7 herds in the single bovine intradermal tuberculin test (BSIT. Two years later it rose to 20.42% in the VH and remained below at 0.75% in the TC. Applying the CIT reduced these rates to only 0.58% in the VH and to 0.25% in the TC ons. Regarding time since each animal joined the program, the proportion of positives to BSIT was variable and, in some cases, significantly different between time points. With regard to the age of vaccination, no significant differences were found between vaccination within the first year of life and afterwards. Vaccinated animals showed seventeen times more reactions than the non-vaccinated in the BSIT, but only four times more in the CIT. In conclusion, comparative intradermal test can be a useful tool to differentiate paratuberculosis vaccine cross-reactions from specific bovine tuberculosis reactions according to the European and Spanish legislation.
Vukcević, Natasa Perković; Babić, Gordana; Segrt, Zoran; Ercegović, Gordana Vuković; Janković, Snezana; Aćimović, Ljubomir
Caffeine is indicated in the treatment of migraine headaches, as well as neonatal apnea and bradycardia syndrome. In mild poisoning, the most prevalent symptoms are nausea, vomiting, diarrhea, tremor, anxiety and headache. In more severe cases, symptoms consist of heart rythym abnormalities, myocardial infarction and seizures. Due to its common lipolytic effect, caffeine is used in mesotherapy, usually in combination with drugs of similar effect. We presented a patient with acute iatrogenic caffeine poisoning. A 51-year-old woman, with preexisting hypertension and hypertensive cardiomyopathy was subjected to cosmetic treatment in order to remove fat by intradermal caffeine injections. During the treatment the patient felt sickness, an urge to vomit, and a pronounced deterioration of general condition. Upon examination, the patient exhibited somnolence, hypotension and nonsustained ventricular tachycardia, which was sufficient enough evidence for further hospitalization. On admission to the intensive care unit the patient was anxious with increased heart rate, normotensive, with cold, damp skin, and visible traces of injection sites with surrounding hematomas on the anterior abdominal wall. Paroxysmal supraventricular tachycardia (PSVT) on electrocardiographic monitoring was found. The laboratory analysis determined a lowered potassium level of 2.1 mmol/L (normal range 3,5 - 5.2 mmol/L), and a toxicological analysis (liquid chromatography with ultraviolet detection) proved a toxic concentration of caffeine in plasma - 85.03 mg/L (toxic concentration over 25 mg/L). On application of intensive therapy, antiarrhythmics, and substitution of potassium, as well as both symptomatic and supportive therapy, there was a significant recovery. The patient was discharged without any sequele within four days. A presented rare iatrogenic acute caffeine poisoning occured due to massive absorption of caffeine from the subcutaneous adipose tissue into the circulation when injected
Full Text Available Introduction. Caffeine is indicated in the treatment of migraine headaches, as well as neonatal apnea and bradycardia syndrome. In mild poisoning, the most prevalent symptoms are nausea, vomiting, diarrhea, tremor, anxiety and headache. In more severe cases, symptoms consist of heart rythym abnormalities, myocardial infarction and seizures. Due to its common lipolytic effect, caffeine is used in mesotherapy, usually in combination with drugs of similar effect. We presented a patient with acute iatrogenic caffeine poisoning. Case report. A 51-year-old woman, with preexisting hypertension and hypertensive cardiomyopathy was subjected to cosmetic treatment in order to remove fat by intradermal caffeine injections. During the treatment the patient felt sickness, an urge to vomit, and a pronounced deterioration of general condition. Upon examination, the patient exhibited somnolence, hypotension and nonsustained ventricular tachycardia, which was sufficient enough evidence for further hospitalization. On admission to the intensive care unit the patient was anxious with increased heart rate, normotensive, with cold, damp skin, and visible traces of injection sites with surrounding hematomas on the anterior abdominal wall. Paroxysmal supraventricular tachycardia (PSVT on electrocardiographic monitoring was found. The laboratory analysis determined a lowered potassium level of 2.1 mmol/L (normal range 3,5 - 5.2 mmol/L, and a toxicological analysis (liquid chromatography with ultraviolet detection proved a toxic concentration of caffeine in plasma - 85.03 mg/L (toxic concentration over 25 mg/L. On application of intensive therapy, antiarrhythmics, and substitution of potassium, as well as both symptomatic and supportive therapy, there was a significant recovery. The patient was discharged without any sequele within four days. Conclusion. A presented rare iatrogenic acute caffeine poisoning occured due to massive absorption of caffeine from the
Full Text Available Abstract Background The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL-4 gene transfected fibroblasts. Methods In University of Pittsburgh Cancer Institute (UPCI protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM or anaplastic astrocytoma (AA received gross total resection (GTR of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN-γ Enzyme-Linked Immuno-SPOT (ELISPOT assay in another human leukocyte antigen (HLA-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA epitope EphA2883–891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants
The administration of a single dose of a multivalent (DHPPiL4R vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus
In conclusion, we demonstrated that a single administration of a minimum titre, multivalent vaccine to dogs of six weeks of age is efficacious and prevents clinical signs and mortality caused by CAV-1 and CDV; prevents clinical signs and significantly reduces virus shedding caused by CAV-2; and prevents clinical signs, leucopoenia and viral excretion caused by CPV.
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 ...
Eaton, Jennifer Wells; Drotman, Michele B; Sales, Rachel M; Arleo, Elizabeth Kagan
In this case report, the history and imaging of two patients with invasive lobular carcinoma (ILC) in the skin are presented, followed by a discussion of both benign and malignant intradermal findings on breast ultrasound. Although the majority of dermal findings are benign, these cases are a reminder that malignancy can manifest within the skin. The purpose of presenting these cases together is to remind breast imagers of the importance of considering malignancy in the differential diagnosis of intradermal lesions on breast ultrasound, especially in special circumstances such as a personal history of breast cancer or associated clinical findings. Copyright © 2017. Published by Elsevier Inc.
Chen, Fan; Yan, Qinying; Yu, Yang; Wu, Mei X
Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin. Copyright © 2017 Elsevier B.V. All rights reserved.
Marina De Filette
Full Text Available West Nile virus (WNV is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime--boost regime with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical. In parallel a heterologous boost with purified recombinant WNV envelope (E protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8(+ specific IFN-γ expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection.
Fenoglio, Daniela; Traverso, Paolo; Parodi, Alessia; Tomasello, Laura; Negrini, Simone; Kalli, Francesca; Battaglia, Florinda; Ferrera, Francesca; Sciallero, Stefania; Murdaca, Giuseppe; Setti, Maurizio; Sobrero, Alberto; Boccardo, Francesco; Cittadini, Giuseppe; Puppo, Francesco; Criscuolo, Domenico; Carmignani, Giorgio; Indiveri, Francesco; Filaci, Gilberto
Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod. The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints. GX301 was administered by intradermally injecting 500 μg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization. No grade 3-4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses. GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.
Vinicius Canato Santana
Full Text Available T-cell based vaccines against human immunodeficiency virus (HIV generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+ T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.
Santana, Vinicius Canato; Almeida, Rafael Ribeiro; Ribeiro, Susan Pereira; Ferreira, Luís Carlos de Souza; Kalil, Jorge; Rosa, Daniela Santoro; Cunha-Neto, Edecio
T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.
Williamson, Eric M L; Chahin, Salim; Berger, Joseph R
Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.
Stading, Ben; Ellison, James A; Carson, William C; Satheshkumar, Panayampalli Subbian; Rocke, Tonie E; Osorio, Jorge E
Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN-luc, negative control) in mice and big brown bats (Eptesicus fuscus). Mice vaccinated and boosted intradermally with 1 x 107 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x107 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x108 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN-luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the efficacy of
Stading, Ben; Ellison, James A.; Carson, William C.; Satheshkumar, Panayampalli Subbian; Rocke, Tonie E.; Osorio, Jorge E.
Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN-luc, negative control) in mice and big brown bats (Eptesicus fuscus). Mice vaccinated and boosted intradermally with 1 x 107 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x107 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x108 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN-luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the
Effects of prophylactic ibuprofen and paracetamol administration on the immunogenicity and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine (PHiD-CV) co-administered with DTPa-combined vaccines in children: An open-label, randomized, controlled, non-inferiority trial.
Falup-Pecurariu, Oana; Man, Sorin C; Neamtu, Mihai L; Chicin, Gratiana; Baciu, Ginel; Pitic, Carmen; Cara, Alexandra C; Neculau, Andrea E; Burlea, Marin; Brinza, Ileana L; Schnell, Cristina N; Sas, Valentina; Lupu, Valeriu V; François, Nancy; Swinnen, Kristien; Borys, Dorota
Prophylactic paracetamol administration impacts vaccine immune response; this study ( www.clinicaltrials.gov : NCT01235949) is the first to assess PHiD-CV immunogenicity following prophylactic ibuprofen administration. In this phase IV, multicenter, open-label, randomized, controlled, non-inferiority study in Romania (November 2010-December 2012), healthy infants were randomized 3:3:3:1:1:1 to prophylactically receive immediate, delayed or no ibuprofen (IIBU, DIBU, NIBU) or paracetamol (IPARA, DPARA, NPARA) after each of 3 primary doses (PHiD-CV at age 3/4/5 months co-administered with DTPa-HBV-IPV/Hib at 3/5 and DTPa-IPV/Hib at 4 months) or booster dose (PHiD-CV and DTPa-HBV-IPV/Hib; 12-15 months). Non-inferiority of immune response one month post-primary vaccination in terms of percentage of infants with anti-pneumococcal antibody concentrations ≥0.2 µg/mL (primary objective) was demonstrated if the upper limit (UL) of the 98.25% confidence interval of difference between groups (NIBU vs IIBU, NIBU vs DIBU) was vaccination in IBU or DIBU group compared to NIBU. Of 850 infants randomized, 812 were included in the total vaccinated cohort. Non-inferiority was demonstrated for both comparisons (UL was vaccine serotypes; exceptions: 6B [NIBU], 23F [IIBU]). However, fever incidence post-primary vaccination in the IIBU and DIBU groups did not indicate a statistically significant reduction. Prophylactic administration (immediate or delayed) of paracetamol decreased fever incidence but seemed to reduce immune response to PHiD-CV, except when given only at booster. Twenty-seven serious adverse events were reported for 15 children; all resolved and were not vaccination-related.
Bianchi, C; Goi, A; Ronchini, A
Hen egg white lysozyme injected intracutaneously into mice inhibits the intradermal diffusion of India Ink. The effect of lysozyme persists in presence of hyaluronidase. Lysozyme injected i.p. into mice inhibits acetic acid (i.p.) induced leakage of Pontamine Sky Blue into the abdominal cavity. The data suggest that lysozyme might be tried for applications outside the microbiological field.
Pool, Shariselle M. W.; Krabbe-Timmerman, Irene S.; Cromheecke, Michel; van der Lei, Berend
OBJECTIVETo assess whether a suture technique in upper blepharoplasty may be the cause of differences in the occurrence of suture abscess formation and focal inflammation.MATERIALS AND METHODSA Level I, randomized controlled trial. The upper blepharoplasty wound was closed with a running intradermal
Full Text Available Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1-/- intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology.
Rose, Amy E; Goldberg, David J
To evaluate the safety and efficacy of intradermal injection of abobotulinumtoxinA for the treatment of oily skin. Twenty-five patients with oily skin were treated in the forehead region with intradermal injections of botulinum toxin. Baseline and post-treatment sebum production was measured using a sebometer. Photographs were taken. Patients were also asked to rate their satisfaction with the treatment in terms of improvement in their oily skin. Treatment with botulinum toxin resulted in significantly lower sebum production at 1 week and 1, 2, and 3 months after injection (p oily skin. [Correction added after online publication 7-Jan-2013: the number of satisfied patients has been updated] Intradermal injection of botulinum toxin significantly reduced sebum production in the forehead region, with a high degree of patient satisfaction. Intradermal botulinum toxin may be an effective treatment to reduce sebum production in patients with oily skin. Larger, randomized, blinded, placebo-controlled studies are warranted. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.
van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W.; Daemen, Toos
The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. PMID:26343186
Stephanie van de Wall
Full Text Available The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV targeting human papillomavirus (HPV. Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7 via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.
Brotherton, Julia M L; Gold, Mike S; Kemp, Andrew S; McIntyre, Peter B; Burgess, Margaret A; Campbell-Lloyd, Sue
In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings. We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine. Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program. Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.
Diemert, David J; Bethony, Jeffrey M; Hotez, Peter J
Hookworm infection caused by the soil-transmitted nematodes Necator americanus and Ancylostoma duodenale is one of the most common parasitic infections worldwide. Although not directly responsible for substantial mortality, it causes significant morbidity in the form of chronic anemia and protein malnutrition. Current global control efforts based on periodic mass anthelmintic administration are unsustainable, and new control strategies must be developed. This review describes progress in the development of vaccines against hookworm infection, including the preclinical and initial clinical testing of the N. americanus Ancylostoma Secreted Protein-2 Hookworm Vaccine. Plans call for eventual development of a vaccine that will combine at least 2 hookworm antigens--one targeting the larval stage of the life cycle and another targeting the adult worm living in the gastrointestinal tract.
Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis CS; Badoual, Cecile; Tartour, Eric
The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites. PMID:25424921
P Safadi, Marco Aurelio; Martinon-Torres, Federico; Weckx, Lily Yin; Moreira, Edson Duarte; da Fonseca Lima, Eduardo Jorge; Mensi, Ilhem; Calabresi, Marco; Toneatto, Daniela
After implementation of routine infant MenC vaccination, MenB remains a serious cause of meningococcal disease, yet to be targeted by vaccination programs in several countries. This study (NCT01339923) investigated the immunogenicity and safety of MenC CRM-conjugated vaccine (MenC-CRM) concomitantly administered with MenB vaccine (4CMenB). Infants (N=251) were randomised 1:1 to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM alone (Group 2) at 3 and 5months (M3, M5) and a booster at 12months of age (M12), and pneumococcal vaccine at M3, M5, M7, M12. Antibody responses to meningococcal vaccines were measured at M3, M6, M12, and M13. Non-inferiority of MenC-CRM response in Group 1 vs Group 2 was demonstrated at M6 and M13, if the lower limit of the 95% confidence interval (LL95%CI) of the difference in percentage of infants with hSBA titres ≥1:8 was >-10%. Sufficiency of MenB response was achieved if LL95%CI of the percentage of infants with hSBA titres ≥1:4 against fHbp, NadA and PorA strains was ≥70% at M6 or ≥75% at M13. Adverse events (AEs) were collected for 7days post-vaccination, and serious AEs (SAEs) and medically attended AEs throughout the study. Non-inferiority of MenC response in Group 1 vs Group 2 (LL95%CI -6.4% [M6]; -5.2% [M13]) and sufficiency of MenB response in Group 1 (LL95%CI 92%, 90%, 89% [M6]; 97%, 92%, 93% [M13] against fHbp, NadA, PorA, respectively) were demonstrated. Higher rates of mild to moderate solicited AEs were reported in Group 1. Unsolicited AEs and SAEs incidences were similar across groups. Concomitant administration of MenC-CRM and 4CMenB in infants was immunogenic, resulting in non-inferior responses against MenC compared to MenC-CRM alone and demonstration of sufficient immune response to MenB, after primary and booster vaccination. Reactogenicity was higher for concomitant vaccines administration, but no safety concerns were identified. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
cells are crucial in the defense against cancer, thus vaccination aimed at generating a large number of functional effector and memory CD8 T cells...annually. Because C. difficile forms spores that are extremely difficult to remove from institutional settings such as hospitals and nursing homes, a...the intradermal model were also disseminated in a research poster at the National MD/PhD Student Conference in July 2015. What do you plan to do
Co-administration of BCG and Diphtheria-tetanus-pertussis (DTP) Vaccinations May Reduce Infant Mortality More Than the WHO-schedule of BCG First and Then DTP. A Re-analysis of Demographic Surveillance Data From Rural Bangladesh.
Aaby, Peter; Andersen, Andreas; Ravn, Henrik; Zaman, K
WHO recommends BCG at birth and diphtheria-tetanus-pertussis (DTP)-containing vaccine at 6, 10 and 14weeks of age. However, BCG and DTP are often co-administered in low-income countries. The health implications have not been examined. We reanalysed data from Matlab, Bangladesh, to examine the influence of co-administration on mortality; 37,894 children born 1986-1999 were followed with registration of vaccinations and survival. Using Cox models, survival was analysed from 6weeks to 9months of age when measles vaccine is given; 712 children died in this age group. We calculated mortality rate ratios (MRR) for children starting the vaccination schedule with BCG-first, BCG+DTP1-first or DTP1-first. Only 17% followed the WHO-schedule with BCG-first. Mortality was 16/1000 person-years for children who initiated the vaccination schedule with BCG+DTP1 but 32/1000 and 20/1000 for children who received BCG-first or DTP-first, respectively. Compared with BCG+DTP1-first and adjusting for background factors, the BCG-first-schedule was associated with 2-fold higher mortality (MRR=1.94 (1.42-2.63)). DTP1 administered after BCG-first was associated with higher mortality than receiving DTP1 with BCG (MRR=1.78 (1.03-3.03)). Co-administration of BCG and DTP may further reduce mortality. Since all observational studies support this trend, co-administration of BCG and DTP should be tested in randomised trials. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola
The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.
Full Text Available DNA, the essential part of the life is making way in to new vaccine technology. Plasmid vectors from the bacteria have revolutionized the world of vaccine design by its new technology DNA vaccines. Small portion of the nucleotides from the pathogen held under the control of promoter in a plasmid vector can be used as a vaccine. DNA vaccines alleviate the odds of the other vaccines by having good hold on both the faces of the immunity. The key to the success of DNA vaccine lies in the route of administration of the vaccine which can be done in many ways. Prime boost strategy is an approach used to boost the action of DNA vaccine. To date there are only four DNA vaccine available in the market. [Vet World 2013; 6(4.000: 228-232
Geier, M R; Stanbro, H; Merril, C R
Twenty samples of commercial vaccines intended for administration to humans were assayed for the presence of bacterial endotoxins by using the Limulus amebocyte lysate test. Sixteen of the vaccines contained more than 0.1 ng of endotoxin per ml (which corresponds to 103 bacterial cell wall equivalents per ml in the undiluted vaccines). These results suggest that at some stage of preparation, the vaccines have contained varying amounts of gram-negative bacteria and may indicate the presence of other bacterial products as well. It might be useful to list the level of endotoxins, phage, and other contaminants on each vaccine lot to facilitate studies on any side effects of these contaminants. Selection of vaccine lots with the least endotoxin might reduce some of the adverse effects of vaccinations. PMID:727776
Matsubara, Akihiro; Shimizu, Yuya; Karamatsu, Katsuo; Yasutomi, Yasuhiro
In the increasing crisis of pandemic of infectious diseases all over the world in recent years, it is the most necessary to develop readily available vaccines even in developing countries. Since many pathogens establish their initial infections through the mucosal surface in our bodies, the induction of mucosal immune responses by vaccines are thought to be important for the prevention of infectious diseases through mucosal site. Oral administration of vaccines has abilities to elicit mucosal immune responses at mucosal tissues with various advantages such as easy skill for administration, less stressful for vaccine recipients and safer than systemic injection. Here, we show our novel strategies for inducing mucosal immune responses by oral vaccine administration.
The purpose of this study was to compare immunologic responses of heifers vaccinated with 10**10 colony-forming units (CFU) of Brucella abortus strain RB51 (SRB51) by standard needle-and-syringe system or a needle-free injection system. Heifers were randomly assigned to control and vaccination gro...
Pearson, Frances E; O'Mahony, Conor; Moore, Anne C; Hill, Adrian V S
There is an urgent need for improvements in vaccine delivery technologies. This is particularly pertinent for vaccination programmes within regions of limited resources, such as those required for adequate provision for disposal of used needles. Microneedles are micron-sized structures that penetrate the stratum corneum of the skin, creating temporary conduits for the needle-free delivery of drugs or vaccines. Here, we aimed to investigate immunity induced by the recombinant simian adenovirus-vectored vaccine ChAd63.ME-TRAP; currently undergoing clinical assessment as a candidate malaria vaccine, when delivered percutaneously by silicon microneedle arrays. In mice, we demonstrate that microneedle-mediated delivery of ChAd63.ME-TRAP induced similar numbers of transgene-specific CD8(+) T cells compared to intradermal (ID) administration with needle-and-syringe, following a single immunisation and after a ChAd63/MVA heterologous prime-boost schedule. When mice immunised with ChAd63/MVA were challenged with live Plasmodium berghei sporozoites, microneedle-mediated ChAd63.ME-TRAP priming demonstrated equivalent protective efficacy as did ID immunisation. Furthermore, responses following ChAd63/MVA immunisation correlated with a specific design parameter of the array used ('total array volume'). The level of transgene expression at the immunisation site and skin-draining lymph node (dLN) was also linked to total array volume. These findings have implications for defining silicon microneedle array design for use with live, vectored vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.
Saporta, Diego; Hurst, David
Objective . To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods . A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results . Posthurricane patients had 34.6 times more positive results ( p hurricanes ( p hurricanes ( p hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.
Mueller, R S; Bettenay, S V; Tideman, L
To determine the most relevant aero-allergens involved in canine atopic dermatitis in southeastern Australia and provide information about these aero-allergens to the general practitioner. Dogs presented to the Animal Skin & Allergy Clinic with history and clinical signs of atopic dermatitis were injected intradermally with 38 different allergens and negative and positive control. Intradermal skin tests in 1000 dogs were retrospectively evaluated. One third of all patients reacted to the house dust mite Dermatophagoides farinae. Allergens reacting in more than 15% of the patients were wheat (Triticum aestivum), sweet vernal (Anthoxanthum odoratum), English couch (Agropyron repens), yellow dock (Rumex crispus), Mexican tea (Chenopodium ambrosioides), plantain (Plantago lanceolata), melaleuca (Melaleuca quinquenervia) and peppercorn (Schimus spp). House dust mites are the most common allergens in canine atopic dermatitis in southeastern Australia and D farinae is involved most frequently. However, a number of grass, weed and tree pollens also are involved regularly.
Sturgill, Tracy L; Giguère, Steeve; Berghaus, Londa J; Hurley, David J; Hondalus, Mary K
Equine neonates have reduced humoral and cell-mediated immune responses compared to adult horses after administration of killed vaccines. As a basis for this study, we hypothesized that newborn foals can mount strong immune responses after vaccination with live Mycobacterium bovis BCG. Healthy 4-day-old foals (n=7), 4-month-old foals (n=7) and adult horses (n=6) were vaccinated once with live M. bovis BCG. Age-matched animals (n=5 per group) were used as unvaccinated controls. Relative vaccine-specific immunoglobulin concentrations and whole blood mRNA expression of IFN-γ, IL-4, and IL-10 were measured prior to and 2, 4, 6, and 8 weeks after vaccination. Eight weeks after vaccination, delayed type hypersensitivity (DTH) responses were assessed by measuring the increase in double skin thickness after intradermal injection of purified protein derivative. Both groups of foals and adult horses responded with a significant increase in vaccine-specific total IgG, IgGa, IgGc, IgG(T), and IgM concentrations. In contrast, only adult horses mounted significant IgGb responses. Vaccine-specific concentrations of total IgG and IgGa were significantly higher in adult horses than in 4-day-old foals whereas IgGc responses were significantly higher in 4-day-old foals than in the other two age groups. Adult horses had significantly higher basal IFN-γ and IL-4 mRNA expression than both groups of foals but vaccination with M. bovis BCG did not significantly increase expression of these cytokines, regardless of age group. Immunized horses had significantly higher DTH responses than age-matched unvaccinated controls. DTH responses were significantly greater in both groups of vaccinated foals than in vaccinated adult horses. Despite a naïve immune system, newborn foals have the ability to mount robust antibody and cell-mediated immune responses to M. bovis BCG. Copyright © 2014 Elsevier Ltd. All rights reserved.
Magiri, R B; Lai, K; Chaffey, A M; Wilson, H L; Berry, W E; Szafron, M L; Mutwiri, G K
Understanding the mechanisms by which adjuvants mediate their effects provide critical information on how innate immunity influences the development of adaptive immunity. Despite being a critical vaccine component, the mechanisms by which adjuvants mediate their effects are not fully understood and this is especially true when they are used in large animals. This lack of understanding limits our ability to design effective vaccines. In the present study, we administered polyphosphazene (PCEP), CpG oligodeoxynucleotides (CpG), emulsigen or saline via an intradermal injection into pigs and assessed the impact on the expression of reported 'adjuvant response genes' over time. CpG induced a strong upregulation of the chemokine CXL10 several 'Interferon Response Genes', as well as TNFα, and IL-10, and a down-regulation of IL-17 genes. Emulsigen upregulated expression of chemokines CCL2 and CCL5, proinflammatory cytokines IL-6 and TNFα, as well as TLR9, and several IFN response genes. PCEP induced the expression of chemokine CCL2 and proinflammatory cytokine IL-6. These results suggest that emulsigen and CpG may promote recruitment of innate immune cells and Th1 type cytokine production but that PCEP may promote a Th-2 type immune response through the induction of IL-6, an inducer of B cell activity and differentiation. Copyright © 2016 Elsevier B.V. All rights reserved.
Mammucari, M.; Maggiori, E; Lazzari, M.; Natoli, S.
Wide variations in the types of pain and response to analgesic pharmacotherapy mean that a variety of treatment strategies are needed. One approach is mesotherapy (intradermal therapy). This consists of microinjections into the skin and is ideally suited to the management of localized pain. Advantages include increasing the duration of drug activity, reduced risk of adverse events and interactions, and possible synergy with other therapies. Mesotherapy provides general practitioners with anot...
Choi, Jin-Sil; Zhu, Yazhen; Li, Hongsheng; Peyda, Parham; Nguyen, Thuy Tien; Shen, Mo Yuan; Yang, Yang Michael; Zhu, Jingyi; Liu, Mei; Lee, Mandy M; Sun, Shih-Sheng; Yang, Yang; Yu, Hsiao-Hua; Chen, Kai; Chuang, Gary S; Tseng, Hsian-Rong
Tattooing has been utilized by the medical community for precisely demarcating anatomic landmarks. This practice is especially important for identifying biopsy sites of nonmelanoma skin cancer (NMSC) due to the long interval (i.e., up to 3 months) between the initial diagnostic biopsy and surgical treatment. Commercially available tattoo pigments possess several issues, which include causing poor cosmesis, being mistaken for a melanocytic lesion, requiring additional removal procedures when no longer desired, and potentially inducing inflammatory responses. The ideal tattoo pigment for labeling of skin biopsy sites for NMSC requires (i) invisibility under ambient light, (ii) fluorescence under a selective light source, (iii) a finite intradermal retention time (ca. 3 months), and (iv) biocompatibility. Herein, we introduce cross-linked fluorescent supramolecular nanoparticles (c-FSNPs) as a "finite tattoo" pigment, with optimized photophysical properties and intradermal retention time to achieve successful in vivo finite tattooing. Fluorescent supramolecular nanoparticles encapsulate a fluorescent conjugated polymer, poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene] (MPS-PPV), into a core via a supramolecular synthetic approach. FSNPs which possess fluorescent properties superior to those of the free MPS-PPV are obtained through a combinatorial screening process. Covalent cross-linking of FSNPs results in micrometer-sized c-FSNPs, which exhibit a size-dependent intradermal retention. The 1456 nm sized c-FSNPs display an ideal intradermal retention time (ca. 3 months) for NMSC lesion labeling, as observed in an in vivo tattoo study. In addition, the c-FSNPs induce undetectable inflammatory responses after tattooing. We believe that the c-FSNPs can serve as a "finite tattoo" pigment to label potential malignant NMSC lesions.
Finken, M.J.J.; Mul, D
6-year-old girl was admitted to our hospital for excessive weight gain. On presentation, she had a typical Cushingoid appearance and hypertension. Laboratory analysis was indicative for an exogenous glucocorticoid source, showing values that were low for serum cortisol and adrenocorticotropin and for 24-h urinary glucocorticoid (metabolite) excretion. Five and 2 months before presentation, she was treated with intradermal triamcinolone acetonide for keloid scars. Recovery of intrinsic cortiso...
Gawdat, Heba I; Hegazy, Rehab A; Fawzy, Marwa M; Fathy, Marwa
A proposal has recently been made regarding the potential adjuvant use of platelet-rich plasma (PRP) with fractional carbon dioxide laser (FCL) for the correction of acne scars. To compare the efficacy and safety of two administration modes of autologous PRP (intradermal injection (ID) and topical application) after FCL with that of FCL alone in the treatment of atrophic acne scars. Thirty patients were randomly divided into two groups. Both underwent split-face therapy. Group 1 was administered FCL followed by ID PRP on one side and FCL followed by ID saline on the other. In group 2, one cheek was treated with FCL followed by ID PRP, and the other received FCL followed by topical PRP. Each patient received 3 monthly sessions. The final assessment took place at 6 months. Combined PRP- and FCL-treated areas had a significantly better response (p = .03), fewer side effects, and shorter downtime (p = .02) than FCL-treated areas, but there were no significant differences in ID- and topical PRP-treated areas in degree of response and downtime (p = .10); topically treated areas had significantly lower pain scores. The current study introduces the combination of topical PRP and FCL as an effective, safe modality in the treatment of atrophic acne scars with shorter downtime than FCL alone and better tolerability than FCL combined with ID PRP. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.
Full Text Available Background and Design: Postoperative scar development is an important problem for patients treated in plastic surgery clinics. Most patients think that continuous intradermal suturing is superior to interrupted suturing because they assume that it creates less scarring. We evaluated scars that form following intradermal and interrupted suturing. This article presents our controlled study that objectively compared the scars on patients' faces using a wound evaluation scale. Materials and Methods: Thirty-five patients, who had undergone operations on the bilateral cheeks, were included in this study. Thirty patients were female; five patients were male. Their mean age was 40.05 years. The average scar evaluation time after surgery was 9.05 months. Elliptical excisions were made on the lesions under local anesthesia. The incisions on the right cheeks were sutured with 6/0 monofilament nonabsorbable sutures using the continuous intradermal suturing technique. The left cheek incisions were sutured with same sutures using the interrupted suturing method. Results: The patients were evaluated 7–11 months after operation (mean: 9.05 months using the Stony Brook Scar Evaluation Scale. A Related Samples T-test was used for statistical evaluation of the differences between the suturing techniques. No significant differences were noted in scar formation between the two suturing methods (p>0.05. Conclusion: We found no differences in scar formation between the two frequently used suturing techniques studied here. We believe that the suturing technique is a less important determinant of scar formation than are other factors.
Norman, James J; Choi, Seong-O; Tong, Nhien T; Aiyar, Avishek R; Patel, Samirkumar R; Prausnitz, Mark R; Allen, Mark G
Limitations with standard intradermal injections have created a clinical need for an alternative, low-cost injection device. In this study, we designed a hollow metal microneedle for reliable intradermal injection and developed a high-throughput micromolding process to produce metal microneedles with complex geometries. To fabricate the microneedles, we laser-ablated a 70 μm × 70 μm square cavity near the tip of poly(lactic acid) (PLA) microneedles. The master structure was a template for multiple micromolded poly(lactic acid-co-glycolic acid) (PLGA) replicas. Each replica was sputtered with a gold seed layer with minimal gold deposited in the cavity due to masking effects. In this way, nickel was electrodeposited selectively outside of the cavity, after which the polymer replica was dissolved to produce a hollow metal microneedle. Force-displacement tests showed the microneedles, with 12 μm thick electrodeposition, could penetrate skin with an insertion force 9 times less than their axial failure force. We injected fluid with the microneedles into pig skin in vitro and hairless guinea pig skin in vivo. The injections targeted 90 % of the material within the skin with minimal leakage onto the skin surface. We conclude that hollow microneedles made by this simple microfabrication method can achieve targeted intradermal injection.
Jacobson, A F
To examine the effect of listening to self-selected music versus an intradermal injection of normal saline solution on the intensity and distress of intravenous (IV) catheter insertion pain. Prospective, randomized, controlled study. Inpatient and outpatient units in 2 university-affiliated southwestern medical centers. One hundred ten adult inpatients and outpatients undergoing IV therapy. Pain intensity, pain distress, and IV insertion difficulty visual analog scales. Patients were randomly assigned to receive an intradermal injection of normal saline solution, listen with headphones to self-selected music, or be in a control group for IV insertion. A MANOVA revealed no statistically significant multivariate or univariate differences in pain by treatment group, but significantly higher pain distress scores with failed IV insertions. The pain intensity and distress scores were significantly higher in the saline solution group when compared with the music and control groups combined. Insertion difficulty was significantly positively correlated with pain intensity and distress for the entire sample, with weak, nonsignificant correlations in the music group. Intradermal unpreserved saline solution contributes to greater pain intensity and distress, greater insertion difficulty, and a higher failure rate than the use of music or routine IV insertion. Listening to preferred music attenuates the effect of insertion difficulty on IV insertion pain. Intravenous insertion attempts were unsuccessful in more than one third of the subjects, resulting in higher pain distress scores. Further research is needed on interventions to reduce IV insertion pain and on factors contributing to IV insertion failure.
Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.
Smith, Billy I; Rieger, Randall H; Dickens, Charlene M; Schultz, Ronald D; Aceto, Helen
To determine the effect of a commercially available multivalent killed virus vaccine on serum neutralizing (SN) and colostrum neutralizing (CN) antibodies against bovine herpesvirus (BHV) type 1 and bovine viral diarrhea virus (BVDV) types 1 and 2 in pregnant dairy cattle. 49 Holstein dairy cattle. PROCEDURES :25 cattle were vaccinated (IM injection) at least 60 days prior to calving (ie, at the end of the lactation period or according to the expected calving date for heifers) and again 5 weeks later. The remaining 24 cattle were not vaccinated (control group). Titers of SN antibodies were measured at the 5-week time point. Titers of SN and CN antibodies were measured at parturition. 5 weeks after initial vaccination, titers of SN antibodies against BHV-1 and BVDV types 1 and 2 were 1:512, 1:128, and 1:2,048, respectively, in vaccinates and 1:64, 1:128, and 1:64, respectively, in unvaccinated controls. Equivalent SN antibody titers at parturition were 1:256, 1:64, and 1:512, respectively, in vaccinates and 1:128, 1:128, and 1:64, respectively, in controls. Median titers of CN antibodies against BHV-1 and BVDV types 1 and 2 were 1:1,280, 1:10,240, and 1:20,480, respectively, in vaccinates and 1:80, 1:1,280, and 1:2,560, respectively, in controls. Titers of antibodies against viral respiratory pathogens were significantly enhanced in both serum (BHV-1 and BVDV type 2) and colostrum (BHV-1 and BVDV types 1 and 2) in cattle receiving a killed virus vaccine (with no adverse reactions) before parturition. To maximize protection of bovine neonates, this method of vaccination should be considered.
Borrego, Belén; Blanco, Esther; Rodríguez Pulido, Miguel; Mateos, Francisco; Lorenzo, Gema; Cardillo, Sabrina; Smitsaart, Eliana; Sobrino, Francisco; Sáiz, Margarita
Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease and a major concern in animal health worldwide. We have previously reported the use of RNA transcripts mimicking structural domains in the non-coding regions of the FMDV RNA as potent type-I interferon (IFN) inducers showing antiviral effect in vivo, as well as their immunomodulatory properties in combination with an FMD vaccine in mice. Here, we describe the enhancing effect of RNA delivery on the immunogenicity and protection induced by a suboptimal dose of a conventional FMD vaccine in pigs. Animals receiving the RNA developed earlier and higher levels of neutralizing antibodies against homologous and heterologous isolates, compared to those immunized with the vaccine alone, and had higher anti-FMDV titers at late times post-vaccination. RNA delivery also induced higher specific T-cell response and protection levels against FMDV challenge. Peripheral blood mononuclear cells from pigs inoculated with RNA and the vaccine had a higher IFN-γ specific response than those from pigs receiving the vaccine alone. When challenged with FMDV, all three animals immunized with the conventional vaccine developed antibodies to the non-structural viral proteins 3ABC and two of them developed severe signs of disease. In the group receiving the vaccine together with the RNA, two pigs were fully protected while one showed delayed and mild signs of disease. Our results support the immunomodulatory effect of these RNA molecules in natural hosts and suggest their potential use for improvement of FMD vaccines strategies. Copyright © 2017 Elsevier B.V. All rights reserved.
Papatsiros, V G; Alexopoulos, C; Kritas, S K; Koptopoulos, G; Nauwynck, H J; Pensaert, M B; Kyriakis, S C
The purpose of this study was to investigate the safety and efficacy of a commercial European porcine reproductive and respiratory syndrome virus (PRRSV)-inactivated vaccine after 18-month use in gilts/sows at a farm with high seroprevalence. In a farrow-to-finish farm with 1100 sows, all sows and gilts were systematically vaccinated with the PRRS-inactivated PROGRESSIS vaccine for a period of 18 months. Farm's reproductive and litter characteristics were longitudinally recorded for this period and historically compared with those of the year prior to vaccination. Serology, employing immunoperoxidase monolayer assay, had confirmed a high prevalence of PRRS-specific antibodies in most age groups within the farm prior to vaccination. Seroprevalence during the experiment ranged between 0% and 100% in weaners and growers, but remained at stable high levels (> 93%) in finishing pigs and gilts throughout all 2-year period of serology measurements. No local or systemic vaccine side effects were noted throughout the trial period. Vaccinations had resulted over time in a significant improvement of sow reproductive performance (e.g. reduction of premature farrowings, abortions and increase of farrowing rate) and litter characteristics (e.g. increase of the number of live born and weaned pigs and decrease of stillborn, mummified, weak and splay-legged piglets). It has also been observed that the higher the degree of immunization of a sow, the better the improvement of her reproductive parameters. Sows after vaccination have shown improved characteristics compared to homoparous sows prior to the application of vaccinations in the farm.
The number of zoospores recoverable from the skin of rats five days after challenge with Dermatophilus congolensis, was reduced if the rats had been injected intradermally with zoospores of this bacterium two weeks previously. The difference between zoospore recovery in vaccinated and control rats was increased when the challenge was applied to scarified skin. Assays involving a 24-hour delay between scarification and challenge gave the greatest difference in zoospore recovery. In rats which had been vaccinated 12 weeks before challenge protection was reduced.
Rose, Kathleen C
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.
He, Yongqun; Xiang, Zuoshuang
In vaccine design, databases and in silico tools play different but complementary roles. Databases collect experimentally verified vaccines and vaccine components, and in silico tools provide computational methods to predict and design new vaccines and vaccine components. Vaccine-related databases include databases of vaccines and vaccine components. In the USA, the Food and Drug Administration (FDA) maintains a database of licensed human vaccines, and the US Department of Agriculture keeps a database of licensed animal vaccines. Databases of vaccine clinical trials and vaccines in research also exist. The important vaccine components include vaccine antigens, vaccine adjuvants, vaccine vectors, and -vaccine preservatives. The vaccine antigens can be whole proteins or immune epitopes. Various in silico vaccine design tools are also available. The Vaccine Investigation and Online Information Network (VIOLIN; http://www.violinet.org ) is a comprehensive vaccine database and analysis system. The VIOLIN database includes various types of vaccines and vaccine components. VIOLIN also includes Vaxign, a Web-based in silico vaccine design program based on the reverse vaccinology strategy. Vaccine information and resources can be integrated with Vaccine Ontology (VO). This chapter introduces databases and in silico tools that facilitate vaccine design, especially those in the VIOLIN system.
The administration of meningitis vaccinations to the college population has recently been the topic of much discussion. Much of the controversy has surrounded the promotion of widespread vaccinations or educational campaigns about the vaccine for incoming freshman students. Recommendations about the use of meningococcal vaccines for college…
Li, Yiping; Kang, H.N.; Babiuk, L.A.
AIM: To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models. METHODS: A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without...... boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation, ELISPOT for the number of interferon-gamma secreting cells, and cytotoxic T lymphocyte assays....... RESULTS: Intradermal injection of E2 DNA vaccine induced strong Th1-like immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination, strategy induced significantly higher E2-specific antibody levels...
Palomares, R A; Hurley, D J; Crum, L T; Rollin, E; Collop, T; Williard, A; Felton, J; Parrish, J; Corbeil, L B
The objective of this study was to determine the level and duration of IgG antibodies induced against killed whole Tritrichomonas foetus and T foetus-purified surface antigen (TF1.17) in serum, vaginal, and uterine secretions after systemic immunization of beef cows with a vaccine containing killed whole T foetus. Twenty nonpregnant beef cows were randomly assigned to vaccine or control groups as follows: Vaccine (n = 10): cows received 2 mL of a commercial vaccine containing killed whole T foetus subcutaneously and a 2-mL booster 2 weeks later. Control (n = 10): cows received 2 mL of sterile saline on the same schedule. Vaginal secretions and blood samples were collected on Days 0, 8, 15, 22, 29, 36, 43, 50, 60, 75, 89, 110, 146, and 182 relative to day of primary vaccination. Uterine flush fluid was collected on Days 0, 15, 29, and 43 after the day of primary vaccination. Samples were assayed for IgG antibodies to the killed whole T foetus and surface antigen TF1.17 using enzyme-linked immunosorbent assay. Serum whole T foetus-specific IgG levels were significantly increased (between Days 15 and 182) following vaccination with T foetus or with saline. No differences between vaccinates and controls in uterine responses to whole-cell antigen were detected. Serum anti-TF1.17 IgG responses to vaccination were significantly higher than Day 0 throughout the immunization period (P IgG levels was observed in vaginal and uterine fluids from Day 15 post vaccination compared to the Day 0 levels. These levels remained significantly elevated in vaginal and uterine fluids through Days 75 (P IgG to the T foetus TF1.17 surface antigen in serum, vaginal secretions, and uterine fluid, which remained elevated through Days 43, 75, and 182 in uterine fluids, vaginal secretions, and serum, respectively. Since purified TF1.17 antigen has been shown to protect against experimental T foetus infection in heifers, the vaccine-induced TF1.17-specific IgG response is likely to be
Surman, Sherri L; Jones, Bart G; Rudraraju, Rajeev; Sealy, Robert E; Hurwitz, Julia L
Our previous studies showed that intranasal vaccination of vitamin A-deficient (VAD) mice failed to induce normal levels of upper respiratory tract IgA, a first line of defense against respiratory virus infection. Here we demonstrate that the impaired responses in VAD animals are corrected by a single intranasal application of retinyl palmitate with the vaccine. Results encourage the clinical testing of intranasal vitamin A supplements to improve protection against respiratory viral disease in VAD populations.
Xu, Ligeng; Xiang, Jian; Liu, Ye; Xu, Jun; Luo, Yinchan; Feng, Liangzhu; Liu, Zhuang; Peng, Rui
Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants.Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual
Panahi, Zeinab; Abdoli, Asghar; Mosayebi, Ghasem; Mahdavi, Mehdi; Bahrami, Fariborz
To evaluate the combined effects of CpG oligodeoxynucleotides (CpG-ODNs) adjuvant and subcutaneous injection route on efficacy of a HIV-1-tat DNA vaccine candidate using BALB/c mice as an animal model. Evaluation of cellular and humoral immunity of mice injected subcutaneously with HIV-1-tat gene cloned into a pcDNA3.1 vector indicated that significant levels of IFN-γ cytokine secretion (900 pg/ml), lymphocyte proliferation (2.5 stimulation index) and IgG2a (1.45 absorbance 450 nm) production could be achieved. These indicators of stimulated cellular immunity were elicited 2 weeks after the last injection (P < 0.05). Formulation of HIV-1-tat DNA vaccine candidate with CpG-ODNs as an adjuvant while administrated subcutaneously are a promising approach to induce effective cellular immunity responses against HIV-1 infection.
Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...
Magalhaes, Isabelle; Sizemore, Donata R.; Ahmed, Raija K.; Mueller, Stefanie; Wehlin, Lena; Scanga, Charles; Weichold, Frank; Schirru, Giulia; Pau, Maria Grazia; Goudsmit, Jaap; Kühlmann-Berenzon, Sharon; Spångberg, Mats; Andersson, Jan; Gaines, Hans; Thorstensson, Rigmor; Skeiky, Yasir A. W.; Sadoff, Jerry; Maeurer, Markus
BACKGROUND: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing
Sil, Arijit; Ravi, Mandyam D; Patnaik, Badri N; Dhingra, Mandeep S; Dupuy, Martin; Gandhi, Dulari J; Dhaded, Sangappa M; Dubey, Anand P; Kundu, Ritabrata; Lalwani, Sanjay K; Chhatwal, Jugesh; Mathew, Leni G; Gupta, Madhu; Sharma, Shiv D; Bavdekar, Sandeep B; Rout, Soumya P; Jayanth, Midde V; D'Cor, Naveena A; Mangarule, Somnath A; Ravinuthala, Suresh; Reddy E, Jagadeesh
Vaccination is considered as the most cost effective method for preventing infectious diseases. Low grade fever is a known adverse effect of vaccination. In India, it is a common clinical practice to prescribe paracetamol either prophylactically or therapeutically to manage fever. Some studies have shown that paracetamol interferes with antibody responses following immunization. This manuscript reports the outcome of a post hoc analysis of data from a clinical trial of a pentavalent vaccine in Indian infants where paracetamol was not used or was used either as prophylaxis or for treatment of fever. Pre and post vaccine antibody levels against Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenzae type B were assessed in no paracetamol and paracetamol groups. The paracetamol group was further divided into prophylactic and treatment groups. Similar rates of seroprotection/seroresponse for anti-D, anti-T, anti-wP, anti-PT, anti-HBs and anti-PRP were observed in all the groups. There was no clear tendency for difference in percentage seroprotection/seroresponse and geometric mean (GM) titers in any of the groups. The study found no evidence that paracetamol usage either as prophylactic or for treatment impact immunological responses to DTwP-HepB-Hib combination vaccine. [Clinical trial registry of India (study registration number CTRI/2012/08/002872)]. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.
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
Slovick, Anna; Douiri, Abdel; Muir, Rachel; Guerra, Andrea; Tsioulos, Konstantinos; Hay, Evie; Lam, Emily P S; Kelly, Joanna; Peacock, Janet L; Ying, Sun; Shamji, Mohamed H; Cousins, David J; Durham, Stephen R; Till, Stephen J
Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy. We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. We randomly assigned 93 adults with grass pollen-induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment. There was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, -172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, -11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense-specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03). Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory
Knobel, D L; Liebenberg, A; Du Toit, J T
This study determined the proportion of captive juvenile and adult African wild dogs (Lycaon pictus) that developed protective titres of rabies neutralising antibodies following ingestion of a chicken head bait/SAG-2 oral rabies vaccine combination. A single chicken head containing 1.8 ml of SAG-2 vaccine (10(8.0) TCID50/ml) in a plastic blister was fed to each of eight adult and three juvenile wild dogs. Bait ingestion resulted in a significant rise in serum neutralising antibody titres. Overall seroconversion rate was eight out of 11 (72.7%), and all the puppies and five out of eight (62.5%) adults showed potentially protective levels of antibodies on day 31. The mean post-vaccination neutralising antibody titre was within the range reported to be protective against challenge with virulent rabies virus in other species.
Karlsson, Ingrid; Borggren, Marie; Rosenstierne, Maiken Worsøe
Background Influenza A virus in swine herds represents a major problem for the swine industry and poses a constant threat for the emergence of novel pandemic viruses and the development of more effective influenza vaccines for pigs is desired. By optimizing the vector backbone and using a needle......-free delivery method, we have recently demonstrated a polyvalent influenza DNA vaccine that induces a broad immune response, including both humoral and cellular immunity. Objectives To investigate the protection of our polyvalent influenza DNA vaccine approach in a pig challenge study. Methods By intradermal...... needle-free delivery to the skin, we immunized pigs with two different doses (500 μg and 800 μg) of an influenza DNA vaccine based on six genes of pandemic origin, including internally expressed matrix and nucleoprotein and externally expressed hemagglutinin and neuraminidase as previously demonstrated...
Gilbert, Sarah C; Moorthy, Vasee S; Andrews, Laura; Pathan, Ansar A; McConkey, Samuel J; Vuola, Jenni M; Keating, Sheila M; Berthoud, Tamara; Webster, Daniel; McShane, Helen; Hill, Adrian V S
T-cell-mediated responses against the liver-stage of Plasmodium falciparum are critical for protection in the human irradiated sporozoite model and several animal models. Heterologous prime-boost approaches, employing plasmid DNA and viral vector delivery of malarial DNA sequences, have proved particularly promising for maximising T-cell-mediated protection in animal models. The T-cell responses induced by this prime-boost regime, in animals and humans, are substantially greater than the sum of the responses induced by DNA or MVA vaccines used alone, leading to the term introduced here of "synergistic" prime-boost immunisation. The insert in our first generation clinical constructs is known as multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We have performed an extensive series of phase I/II trials evaluating various prime-boost combination regimens for delivery of ME-TRAP in over 500 malaria-naïve and malaria-exposed individuals. The three delivery vectors are DNA, modified vaccinia virus Ankara (MVA) and, more recently, fowlpox strain 9 (FP9). Administration was intra-epidermal and intramuscular for DNA and intradermal for MVA and FP9. Doses of DNA ranged from 4 microg to 2mg. Doses of MVA were up to 1.5 x 10(8) plaque forming units (pfu) and of FP9, up to 1.0 x 10(8)pfu. Further trials employing bacille Calmette-Guérin (BCG) as the priming agent and MVA expressing antigen 85A of Mycobacterium tuberculosis as the boosting agent has extended the scope of synergistic prime-boost vaccination. In this review we summarise the safety, immunogenicity and efficacy results from these malaria and tuberculosis vaccine clinical trials.
Richter, Dirk; Stoff, Alexander; Ramakrishnan, Venkat; Exner, Klaus; Jernbeck, Jan; Blondeel, Phillip N
A novel topical skin adhesive system was developed to close the outermost layer of skin in an expeditious manner. To determine its clinical utility, a clinical investigation was undertaken to demonstrate equivalence of a new adhesive skin closure system (Prineo Skin Closure System) to intradermal sutures in wound closure. The investigation included 83 patients who underwent elective abdominoplasty, circumferential body lift procedures, and breast reconstruction with deep inferior epigastric perforator flaps. Incisions were divided in half, and each half was randomized to wound closure with the new skin closure system, including a pressure-sensitive adhesive mesh tape for wound edge approximation and next-generation cyanoacrylate or intradermal sutures. Postoperative evaluations took place at 24 hours, 7 days, 12 to 25 days, 90 days, 6 months, and 12 months. The new skin closure system was found to be equivalent to intradermal sutures for the continuous approximation of wounds. The upper limit of the two-sided 90 percent confidence interval for difference in proportions was 10.9 percent. The mean time to closure for the new skin closure system was 1.46 minutes, approximately 5 minutes faster than that for intradermal sutures (p sutures for full-thickness surgical incisions with regard to safety and effectiveness. The ease and speed of application contribute to shortened operative times (4.5 times faster than intradermal sutures).
Vandermeulen, Corinne; Theeten, Heidi; Rathi, Niraj; Kuriyakose, Sherine; Han, Htay Htay; Sokal, Etienne; Hoppenbrouwers, Karel; Van Damme, Pierre
Regular booster vaccination might be necessary throughout life to protect against pertussis infection. Nevertheless the duration of protection after booster vaccination remains unclear. In this study, antibody persistence up to 10 years after previous vaccination of adolescents (N=478) with combined reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (dTpa, Boostrix™, GlaxoSmithKline Belgium) containing 0.5mg, 0.3mg or 0.133mg of aluminium was assessed. The immunogenicity, reactogenicity and safety of a decennial booster dTpa dose were also investigated. Young adults vaccinated as adolescents in the initial booster study were invited to participate in an assessment of antibody persistence at years 8.5 and 10, and to receive a dTpa booster dose at year 10 with immunogenicity assessment one month later. Those who originally received the 0.5mg or 0.3mg formulations received the same vaccine at year 10. Those in the 0.133mg group received the 0.5mg formulation. Reactogenicity and safety endpoints were captured until 30 days after booster vaccination. Prior to the decennial booster at year 8.5 and year 10, all participants had seroprotective antibodies for diphtheria (ELISA or neutralisation assay) and tetanus. At least 77.8% were seropositive for anti-pertussis toxin (PT) antibodies at year 8.5 and 82.8% at year 10. All participants were seropositive for antibodies for filamentous haemagglutinin and pertactin at both time points. The decennial booster dose induced robust increases in antibody GMCs to all antigens. The post-booster anti-PT geometric mean concentration was 82.5EL.U/ml (95%CI 67.0-101.6) and 124.0 (103.5-148.5) in the 0.3mg and 0.5mg groups, respectively. The reactogenicity and safety profile of the decennial booster dose was consistent with the known safety profile of dTpa. No serious adverse events were reported. Decennial booster vaccination with either of the two licensed formulations of dTpa was highly immunogenic and well
Mammucari, Massimo; Maggiori, Enrica; Lazzari, Marzia; Natoli, Silvia
Wide variations in the types of pain and response to analgesic pharmacotherapy mean that a variety of treatment strategies are needed. One approach is mesotherapy (intradermal therapy). This consists of microinjections into the skin and is ideally suited to the management of localized pain. Advantages include increasing the duration of drug activity, reduced risk of adverse events and interactions, and possible synergy with other therapies. Mesotherapy provides general practitioners with another tool for the treatment of local pain. However, it is important to provide patients with full details of the pros and cons of this approach and obtain informed patient consent.
Ilum, Lars; Bak, Martin; Olsen, K E
-sectioning and immunohistochemical staining for cytokeratin. In one case a benign epithelial inclusion was found. The sentinel node was false negative in 9.1% of cases. The consensus from the literature is that the best results are achieved using a combination of dye and isotopic techniques.......In a series of 161 consecutive breast cancer operations, intradermal injection of Patent Blue was used to localize the sentinel node (SN). The surgical localization rate was 60%. Including the blue lymph nodes found by the pathologist, localization rate was 70%. After the first 103 operations...
The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.
Goldman, Candice; Rosser, Edmund; Petersen, Annette; Hauptman, Joe
The ability to use ciclosporin (Atopica®: Novartis Animal Health, Greensboro, NC, USA) prior to intradermal testing (IDT) would help avoid exacerbation of clinical disease that can be associated with drug withdrawal. This study evaluated the effects of 30 days of administration of ciclosporin at a dose of 5 mg/kg once daily on IDT reactivity (immediate phase reactions) in a group of dogs with atopic dermatitis (AD) with initial positive IDT reactions. 16 dogs diagnosed with AD were included in the study. Eight dogs (group A) were treated with ciclosporin orally at 5 mg/kg once daily for 30 days. Eight dogs (group P) were treated with a placebo orally once daily for 30 days. IDT was performed at day 0 and day 30 on all dogs enrolled using a standardized panel of 45 aqueous allergens (Greer Laboratories, Lenoir, NC, USA) appropriate to our geographical region. IDT reactivity was assessed by both subjective and objective methods at 15 min post-intradermal injection. Serum for allergen-specific immunoglobulin (IgE) serology was obtained at day 0 and day 30. The study was designed as a double-blinded, placebo-controlled, cross-over study. Data were analysed using a split-plot analysis of variance with the grouping factor of treatment and the repeat factor of time (SAS System for Windows). At week 4, ciclosporin did not have a statistically significant effect on IDT reactivity or serology results. It therefore appears that, no withdrawal is recommended to evaluate immediate phase reactions. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.
Full Text Available Immunization with DTP vaccine (diphtheria, tetanus and pertussis is a part of the vaccination calendar offered in childhood. Adverse allergic reactions vary from minimal urticarial reactions to life-threatening anaphylaxis. In infancy these reactions usually interrupt the vaccination calendar, but immunization in these children should be done. At the University Children's Hospital of Belgrade, a group of 137 children with suspected allergic anaphylactic reaction to DTP, DT, TT and monopertussis vaccine was studied for the last six years. Skin (prick and intradermal tests were performed with corresponding vaccine. If both tests were negative, the vaccine could be given as a single dose of 0.5 ml. If one of these tests were positive desensitization with vaccine could be done (according to the protocol described by Carey and Meltzer. In one group of 52 children three days before desensitization, premedication with antihistamines, was done, whereas in the other group of 52 children premedication was not done. Two (3.8% children in a group of 52 children with premedication had a minor (local reaction after vaccination and 50 children (96.2% had no reaction after vaccination, whereas no children (0% had systemic reaction after desensitization.
Nordquist, Lina; Roxhed, Niclas; Griss, Patrick; Stemme, Göran
Good glycaemic control is essential to minimize the risk for diabetes-induced complications. Also, compliance is likely to be higher if the procedure is simple and painless. This study was designed to validate painless intradermal delivery via a patch-like microneedle array. Diabetes was induced by an intravenous injection of streptozotocin (50 mg/kg bw) in adult male Sprague Dawley rats. Plasma insulin and blood glucose were measured before, during and after subcutaneous or intradermal (microneedles) infusion of insulin (0.2 IU/h) under Inactin-anaesthesia. Before insulin administration, all animals displayed a pronounced hyperglycaemia (19 +/- 1 mM; 359 mg/dl). Administration of insulin resulted in a reduced plasma glucose independently of administration route (subcutaneous 7.5 +/- 4.2, n = 9, and intradermal 11 +/- 1.8, n = 9 after 240 min), but with less errors of the mean in the intradermal group. In the intradermal group, plasma insulin was increased in all latter measurements (72 +/- 22, 81 +/- 34, and 87 +/- 20 microIU/ml), as compared to the first measurement (26 +/- 13). In the subcutaneous group, plasma insulin was elevated during the last measurement (to 154 +/- 3.5 microIU/ml from 21 +/- 18). This study presents a novel possibility of insulin delivery that is controllable and requires minimal training. This treatment strategy could improve compliance, and thus be beneficial for patients' glycaemic control.
Birk, Nina Marie; Nissen, Thomas Nørrelykke; Ladekarl, Monica
Background: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact...... of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. Methods: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG...... vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence...
Birk, Nina Marie; Nissen, Thomas Nørrelykke; Ladekarl, Monica
BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact...... of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. METHODS: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG...... vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence...
Burgdorf, S K; Fischer, A; Claesson, M H
Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine...... contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic....
Shekalaghe, Seif; Rutaihwa, Mastidia; Billingsley, Peter F.; Chemba, Mwajuma; Daubenberger, Claudia A.; James, Eric R.; Mpina, Maximillian; Ali Juma, Omar; Schindler, Tobias; Huber, Eric; Gunasekera, Anusha; Manoj, Anita; Simon, Beatus; Saverino, Elizabeth; Church, L. W. Preston; Hermsen, Cornelus C.; Sauerwein, Robert W.; Plowe, Christopher; Venkatesan, Meera; Sasi, Philip; Lweno, Omar; Mutani, Paul; Hamad, Ali; Mohammed, Ali; Urassa, Alwisa; Mzee, Tutu; Padilla, Debbie; Ruben, Adam; Lee Sim, B. Kim; Tanner, Marcel; Abdulla, Salim; Hoffman, Stephen L.
Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious. PMID:25070995
Strohmeier, B; Aberer, W; Bokanovic, D; Komericki, P; Sturm, G J
According to current guidelines, skin testing for hymenoptera venom allergy should be performed in a stepwise manner, maintaining 15- to 20-min intervals between the injections of venom. Given the long-winded procedure of sequential skin testing, we retrospectively explored the safety of simultaneous intradermal testing. Four hundred and seventy-eight consecutive patients with a convincing history of an anaphylactic reaction after a hymenoptera sting were tested. All venom concentrations (0.02 ml of 0.001, 0.01, 0.1, and 1.0 μg/ml of honey bee and wasp venom) were administered simultaneously to the skin. Four hundred and seventy-two (98.7%) patients tolerated the simultaneous intradermal test without any side-effects. Only three subjects (0.6%) had a presumed allergic reaction during the test; another three reactions were considered vasovagal. Our skin test protocol with four simultaneously injected concentrations of two hymenoptera venoms is safe and permits the investigator to draw rapid conclusions about the individual's sensitization pattern. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
Full Text Available Objective. To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods. A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results. Posthurricane patients had 34.6 times more positive results (p<0.0001 at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes (p<0.0001; average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes (p<0.0001. The posthurricane population was younger (p<0.001 and included more patients with asthma or lower respiratory symptoms (p<0.05. Conclusion. Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists’ hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.
Caspard, Herve; Wise, Robert P; Steffey, Amy; Brody, Robert S
To estimate the proportion of live-attenuated influenza vaccine (LAIV) doses administered beyond expiry date in children and adolescents during influenza seasons 2013-2014 and 2014-2015 in the UK. This was a retrospective cohort study. Two cohorts of children and adolescents who received LAIV from 1 September 2013 to 31 March 2014 and from 1 September 2014 to 31 March 2015 and aged 2-17 years at time of LAIV administration were identified from the Clinical Practice Research Datalink (CPRD). More than 500 primary care practices in the UK. Proportions of vaccine doses administered beyond expiry date were assessed among 47 396 and 67 099 LAIV recipients with a documented vaccine lot identifier in influenza seasons 2013-2014 and 2014-2015, respectively. None. Administrations of expired LAIV were ascertained by comparison of vaccination dates in CPRD records with expiration dates in AstraZeneca/MedImmune lot distribution data. Overall, 245 LAIV recipients, 80 in 2013-2014 and 165 in 2014-2015, received a dose after its expiration date, yielding proportion estimates of 1.7 per 1000 doses (95% CI 1.3 to 2.1) in season 2013-2014 and 2.5 per 1000 (95% CI 2.1 to 2.8) in season 2014-2015. This proportion increased above 1.0% after December during each season. Most (84% in influenza season 2013-2014 and 59% in influenza season 2014-2015) received an expired dose <30 days after its expiration date. The proportion was higher in London (relative risk 1.93 (95% CI 1.25 to 2.99)) and when the number of LAIV recipients registered in the practice was lower than the median number per practice (relative risk 2.69 (95% CI 1.99 to 3.62)). Administration of expired LAIV doses occurs infrequently. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Lanes, Stephan; Quinlan, Scott C; Mast, T Christopher; Greenland, Sander; Holick, Crystal N
RotaTeq® pentavalent human rotavirus vaccine (RV5) is effective against rotavirus illness and rotavirus-related hospitalizations and death. Effectiveness depends on adherence to the dosing schedule, which includes 3 doses at ages 2, 4 and 6 months. Two studies have used automated claims databases to estimate the proportion of vaccinated infants who complete the dosing schedule, but excluded from analysis vaccinated infants who were not enrolled in the database for a sufficient period to observe all 3 doses. Restricting study populations based on duration of follow-up can introduce bias if a large number of subjects are excluded due to insufficient follow-up, and if their outcomes differ from subjects who are included. To address the possibility that exclusions may have been extensive and led to biased estimates of completion rates, we conducted a claims database analysis in the HealthCore Integrated Research Database(SM) to evaluate the proportion of rotavirus vaccinated infants who completed the 3 dose series of RV5. We evaluated potential error introduced by restricting analyses to infants with complete follow-up by estimating completion rates among infants with complete follow-up, and using Kaplan-Meier analyses to estimate completion rates including infants with incomplete follow-up. The inclusion criterion requiring continuous enrollment for the first year of life resulted in only 108,533 (40%) of 233,143 vaccinated infants from 2006-2012 being included in the analysis. After relaxing inclusion criteria, we were able to include 86% of vaccinated infants. The estimated completion rate among infants with continuous enrollment from birth through the first year of life was 78.1% (95% confidence limits [CLs] 77.8%, 78.3%), and among the expanded population the estimated completion rate was 77.4% (95% CLs 77.2%, 77.6%). These results indicate that most infants were not followed in the database through the first year of life, but the impact of excluding infants
Mucosal Administration of CpG Oligodeoxynucleotide Elicits Strong CC and CXC Chemokine Responses in the Vagina and Serves as a Potent Th1-Tilting Adjuvant for Recombinant gD2 Protein Vaccination against Genital Herpes
Tengvall, Sara; Lundqvist, Annika; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.
Although sexually transmitted pathogens are capable of inducing pathogen-specific immune responses, vaginal administration of nonreplicating antigens elicits only weak, nondisseminating immune responses. The present study was undertaken to examine the potential of CpG-containing oligodeoxynucleotide (CpG ODN) for induction of chemokine responses in the genital tract mucosa and also as a vaginal adjuvant in combination with glycoprotein D of herpes simplex virus type 2 (HSV-2) for induction of antigen-specific immune responses. We found that a single intravaginal administration of CpG ODN in mice stimulates a rapid and potent response of CC chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES as well as of CXC chemokines MIP-2 and IP-10 in the vagina and/or the genital lymph nodes. Importantly, intravaginal vaccination with recombinant gD2 in combination with CpG ODN gave rise to a strong antigen-specific Th1-like immune response in the genital lymph nodes as well as the spleens of the vaccinated mice. Further, such an immunization scheme conferred both systemic and mucosal immunoglobulin G antibody responses as well as protection against an otherwise lethal vaginal challenge with HSV-2. These results illustrate the potential of CpG ODN for induction of potent chemokine responses in the genital tract and also as a vaginal adjuvant for generation of Th1-type mucosal and systemic immune responses towards a nonreplicating antigen derived from a sexually transmitted pathogen. These data have implications for the development of a mucosal vaccine against genital herpes and possibly other sexually transmitted diseases. PMID:16699008
N. F. Snegova
Full Text Available The article summarizes data on methods and opportunities of frequently ailing children rehabilitation. Authors mark a leading role of vaccination against pneumotropic infections. Questions of successful interaction between doctor and frequently ailing child’s parents are highlighted. The observation of 94 children 3 months — 3 years old (patients had different types of initial immune insuffiiency, neurological pathology, recurrent obstructive bronchitis, or were included in group of frequently ailing children vaccinated with Pentaxim was performed. 94% of children showed asymptomatic postvaccinal period. Fever up to 39°C occurred in 2.3% of patients. Local reactions (diameter was not over 3–5 cm developed in 1.7% of children. There was no any case of postvaccinal complication. Evaluation of vaccine’s reactogenity proves its safety and reasonability in immunization against pertussis, diphtheria, tetanus, poliomyelitis, Haemophilis influenzae type b in children of different health state including those with concomitant diseases.
Galgani, Ilaria; Bunge, Eveline M; Hendriks, Lisa; Schludermann, Christopher; Marano, Cinzia; De Moerlooze, Laurence
Tick-borne encephalitis (TBE), which is endemic across large regions of Europe and Asia, is most effectively prevented through vaccination. Three-dose primary TBE vaccination schedules are either rapid (0,7,21-days) or conventional (0,28-84-days, 9-12-months). The second dose can also be administered at 14 days for faster priming and sero-protection). Areas covered: We used a three-step selection process to identify 21 publications comparing the immunogenicity and/or safety of different schedules. Expert commentary: Priming with two or three TBE vaccine doses was highly immunogenic. After conventional priming (0-28 days), 95% adults and ≥95% children had neutralization test (NT) titers ≥10 at 14 days post-dose-2 compared with 92% adults and 99% children at 21 days post-dose-3 (rapid schedule). Most subjects retained NT titers ≥10 at day 300. A single booster dose induced a strong immune response in all subjects irrespective of primary vaccination schedule or elapsed time since priming. GMT peaked at 42 days post-dose-1 (i.e., 21 days post-dose 3 [rapid-schedule], or 14-28 days post-dose-2 [conventional-schedule]), and declined thereafter. Adverse events were generally rare and declined with increasing doses. In the absence of data to recommend one particular schedule, the regimen choice will remain at the physician's discretion, based on patient constraints and availability.
Serrano, Miriam; Elguezabal, Natalia; Sevilla, Iker A; Geijo, María V; Molina, Elena; Arrazuria, Rakel; Urkitza, Alfonso; Jones, Gareth J; Vordermeier, Martin; Garrido, Joseba M; Juste, Ramón A
Paratuberculosis vaccination in cattle has been restricted due to its possible interference with the official diagnostic methods used in tuberculosis eradication programs. To overcome this drawback, new possibilities to detect Mycobacterium bovis infected cattle in paratuberculosis vaccinated animals were studied under experimental conditions. Three groups of 5 calves each were included in the experiment: one paratuberculosis vaccinated group, one paratuberculosis vaccinated and M. bovis infected group and one M. bovis infected group. The performance of the IFN-gamma release assay (IGRA) and the skin test using conventional avian and bovine tuberculins (A- and B-PPD) but also other more specific antigens (ESAT-6/CFP10 and Rv3615c) was studied under official and new diagnostic criteria. Regarding the IGRA of vaccinated groups, when A- and B-PPD were used the sensitivity reached 100% at the first post-challenge sampling, dropping down to 40-80% in subsequent samplings. The sensitivity for the specific antigens was 80-100% and the specificity was also improved. After adapting the diagnostic criteria for the conventional antigens in the skin test, the ability to differentiate between M. bovis infected and non-infected animals included in paratuberculosis vaccinated groups was enhanced. Taking for positive a relative skin thickness increase of at least 100%, the single intradermal test specificity and sensitivity yielded 100%. The comparative intradermal test was equally accurate considering a B-PPD relative skin increase of at least 100% and greater than or equal to that produced by A-PPD. Using the specific antigens as a proteic cocktail, the specificity and sensitivity reached 100% considering the new relative and absolute cut-offs in all experimental groups (Δ≥30% and Δmm ≥ 2, respectively). Results suggest that the interference caused by paratuberculosis vaccination in cattle could be completely overcome by applying new approaches to the official tuberculosis
Tomar, Jasmine; Born, Philip A; Frijlink, Henderik W; Hinrichs, Wouter L J
Cold-chain requirements, limited stockpiling potential and the lack of potent immune responses are major challenges of parenterally formulated influenza vaccines. Decreased cold chain dependence and stockpiling can be achieved if vaccines are formulated in a dry state using suitable excipients and drying technologies. Furthermore, having the vaccine in a dry state enables the development of non-parenteral patient friendly dosage forms: microneedles for transdermal administration, tablets for oral administration, and powders for epidermal, nasal or pulmonary administration. Moreover, these administration routes have the potential to elicit an improved immune response. This review highlights the rationale for the development of dried influenza vaccines, as well as processes used for the drying and stabilization of influenza vaccines; it also compares the immunogenicity of dried influenza vaccines administered via non-invasive routes with that of parenterally administered influenza vaccines. Finally, it discusses unmet needs, challenges and future developments in the field of dried influenza vaccines.
Carson, Connor; Antoniou, Maria; Ruiz-Argüello, Maria Begoña; Alcami, Antonio; Christodoulou, Vasiliki; Messaritakis, Ippokratis; Blackwell, Jenefer M; Courtenay, Orin
Previous studies demonstrated safety, immunogenicity and efficacy of DNA/modified vaccinia virus Ankara (MVA) prime/boost vaccines expressing tryparedoxin peroxidase (TRYP) and Leishmania homologue of the mammalian receptor for activated C kinase (LACK) against Leishmania major challenge in mice, which was consistent with results from TRYP protein/adjuvant combinations in non-human primates. This study aimed to conduct safety and immunogenicity trials of these DNA/MVA vaccines in dogs, the natural reservoir host of Leishmania infantum, followed-up for 4 months post-vaccination. In a cohort of 22 uninfected outbred dogs, blinded randomised administration of 1000 microg (high dose) or 100 microg (low dose) DNA prime (day 0) and 1x10(8)pfu MVA boost (day 28) was shown to be safe and showed no clinical side effects. High dose DNA/MVA vaccinated TRYP dogs produced statistically higher mean levels of the type-1 pro-inflammatory cytokine IFN-gamma than controls in whole blood assays (WBA) stimulated with the recombinant vaccine antigen TRYP, up to the final sampling at day 126, and in the absence of challenge with Leishmania. TRYP vaccinated dogs also demonstrated significantly higher TRYP-specific total IgG and IgG2 subtype titres than in controls, and positive in vivo intradermal reactions at day 156 in the absence of natural infection, observed in 6/8 TRYP vaccinated dogs. No significant increases in IFN-gamma in LACK-stimulated WBA, or in LACK-specific IgG levels, were detected in LACK vaccinated dogs compared to controls, and only 2/9 LACK vaccinated dogs demonstrated DTH responses at day 156. In all groups, IgG1 subclass responses and antigen-specific stimulation of IL-10 were similar to controls demonstrating an absence of Th2/T(reg) response, as expected in the absence of in vivo restimulation or natural/experimental challenge with Leishmania. These collective results indicate significant antigen-specific type-1 responses and in vivo memory phase cellular immune
Emmanuel D. Jadhav
Full Text Available IntroductionThe resurgence of vaccine preventable diseases occurs more often among intentionally unvaccinated individuals, placing at direct risk young adults not caught up on vaccinations. The objectives of this study were to characterize the sociodemographic characteristics of young adults with and without vaccination waivers and identify their perceived benefits, barriers, and influencers of vaccination.MethodsYoung adults (n = 964 from a Midwestern rural university responded to a survey (fall 2015—spring 2016 designed to identify their perception toward vaccination. Instrument consistency was measured using the Cronbach α-scores. The Chi-square test was used to test any sociodemographic differences and Mann–Whitney U-tests results for differences between exempt and non-exempt students. Analysis occurred in spring 2017.ResultsA little over one-third of young adults with a vaccination waiver were not up to date on their vaccinations, and think that vaccinations can cause autism. The biggest identifiable benefit was effective control against disease. The surveyed young adults ranked the out of pocket cost associated with vaccination as the most important barrier and safe and easy to use vaccines as the most important influencer of vaccination.ConclusionYoung adults who have had a vaccination waiver appear to not be up to date on their vaccinations. Vaccine administration programs, such as university campus clinics, would benefit from addressing perceptions unique to young adults with and without a vaccine waiver. This would subsequently better provide young adults a second shot for getting appropriately caught up on vaccinations.
Demuth, Peter C.; Min, Younjin; Huang, Bonnie; Kramer, Joshua A.; Miller, Andrew D.; Barouch, Dan H.; Hammond, Paula T.; Irvine, Darrell J.
DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These ‘multilayer tattoo’ DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.
Kuate Defo, Zenas; Lee, Byong
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.
Sloet van Oldruitenborgh-Oosterbaan, M.M.; Poppel, van M.; Raat, de I.J.; Boom, van den R.; Savelkoul, H.F.J.
Intradermal tests using a Culicoides nubeculosus extract have proven unreliable for diagnosis of equine insect bite hypersensitivity (IBH) in the Netherlands. The aim of this study was to evaluate the diagnostic value of an extract derived from the Dutch species C. obsoletus and C. pulicaris.
Dhaduk, Kishor M; Unadkat, Sumit V; Katharotiya, Pooja R; Mer, Ankit R; Chaudhary, Monika C; Prajapati, Mrudul M
Rabies is a preventable neglected public health problem and associated with multiple cultural, religious, and social practices, myths in our country. There is a lack of organized surveillance system to measure the incidence of animal bite and human rabies as well as to evaluate cost-saving of different routes, regimen, and types of antirabies vaccines (ARV)/immunoglobulin available in India. The objective of this study is to know dropout rate in intradermal (i.d.) ARV regimen among animal bite and to analyze the utilized volume of ARV by a different route of vaccine administration. A total of 250 animal bite victims were followed up at ARV Clinic (ARVC). Volume utilization of i.d. route over intramuscular (i.m.) route was analyzed among the patients who attended ARVC during the past 2 years. Total dropout and delayed compliance rates of ARV regimen among different group were compared by Chi-square test. The i.d. route was about five times more volume and cost-saving than i.m. route. The majority of victims belonged to 15-30 years (27.60%) and children <15 years (26.40%) and had wound at their lower limbs (85%) mainly bitten by dogs (98%). Thirty-four percent total dropout and 31.5% delayed compliance observed particularly during the last dose of i.d. regimen. There was no significant difference in dropout rates among different demographic groups. Half of the victims practiced wound toilet on the same day of bite. Only 68% received the first dose of ARV within 24 h of the exposure. Children and young adults are at higher risk of having dog bite. I.d. ARV regimen is more volume and cost-saving than i.m. one and proper counseling and follow-up should be arranged to complete the vaccination schedule.
... doctorMost kids have no problems with the polio vaccine. However, call your doctor if your child has any reaction after getting the vaccine. Call ... Tell the doctor when (day and time) your child received the vaccine. You also should file a Vaccine Adverse Event ...
Tauberg, James A. H.; Nique, Thomas A.; Giovannitti, Joseph A.
A case is reported in which chronic urticaria developed following local anesthetic administration in a 21-year old Chinese-American male who had presented for routine dental care. An in-depth medical history and intradermal skin-testing failed to disclose a reason for this reaction. Referral to an allergist revealed a previously unknown underlying emotional tension which contributed to the development of chronic urticaria. A brief trial of hydroxyzine (Vistaril), an antihistaminic and anxioly...
Khairutdinov, Vladislav R; Mikhailichenko, Anastasiya F; Belousova, Irena E; Kuligina, Ekatherina Sh; Samtsov, Alexey V; Imyanitov, Evgeny N
Psoriasis is a common immune-mediated chronic inflammatory disease of the skin and joints, affecting 1-3% of the population. It is generally accepted that the pathogenesis of psoriasis involves accumulation of effector T-cells within lymph nodes and their subsequent migration into the skin through the blood system. Here we provide evidence that psoriatic plaque itself may serve as a source of inflammatory T-cells. We examined the intradermal proliferation of T-cells and the number of effector/memory (CD45RO+) T-cells in the skin of psoriatic patients at different periods of the disease. Skin samples were obtained from 41 patients with progressive psoriatic lesions; 18 of these patients also donated skin specimens during the remission of the disease. The control group consisted of 16 healthy subjects. Ki-67 immunohistochemical staining was applied to detect proliferating cells, CD3ε served as a T-cell marker, and CD45RA and CD45RO antibodies were utilized to discriminate between naive and effector/memory T-cells, respectively. Progressive psoriatic lesions demonstrated Ki67 staining both in keratinocytes and in the CD3ε+ cells of dermal infiltrate. Median count of CD45RO+ cells per microscopic field was 15 in healthy controls, 59 in patients in remission and 208 in progressive psoriatic plaques. The observed differences demonstrated high level of statistical significance. Limited number of analyzed patients. Progressive phase of psoriasis is characterized by intradermal proliferation of T-cells. Spots of regressed psoriatic lesions contain high number of CD45RO+ cells, which are likely to render an immunological memory.
Mönkäre, Juha; Reza Nejadnik, M; Baccouche, Khalil; Romeijn, Stefan; Jiskoot, Wim; Bouwstra, Joke A
Dissolving microneedles are an attractive approach for non-invasive delivery of drugs via the skin, particularly when the doses are in the microgram or low-milligram range. The aim of the study was to develop hyaluronan-based, monoclonal IgG-loaded microneedles for intradermal delivery enabling efficient penetration and rapid dissolution in the skin while preserving protein stability. Microscopic analysis showed successful preparation of sharp microneedles with the tip length of ~280 μm and with up to 10% (w/w) of IgG content. The water content of the microneedles was ~12% and was not affected by the protein content. The protein distribution was uniform within microneedle tips and individual arrays but some array-to-array variation of IgG level within a single preparation batch was detected. After dissolution of microneedle arrays in PBS, N80% of protein was recovered and no conformational changes were detected by fluorescence spectroscopy. At submicron level, only weak and reversible interaction between HA and IgG was found by asymmetric flow field flow fractionation analysis after the dissolution of prepared microneedles. Although, the formation of insoluble micron-size particles was detected by flow imaging microscopy the IgG amount incorporated into these particles was negligible (b5%). Finally, microneedles were able to penetrate into the epidermis of ex vivo human skin followed by the rapid dissolution of the microneedle tips in the skin. After 10 min of application, the majority of the original tip length was dissolved and IgG and hyaluronan were co-deposited until a depth of 150-200 μm in the skin. In conclusion, developed hyaluronan-based dissolving microneedles allow rapid noninvasive intradermal protein delivery.
Mocan, Teodora; Matea, Cristian; Tabaran, Flaviu; Iancu, Cornel; Orasan, Remus; Mocan, Lucian
Therapeutic cancer vaccines (or active immunotherapy) aim to guide the patient's personal immune system to eradicate cancer cells. An exciting approach to cancer vaccines has been offered by nanoscale drug delivery systems containing tumor associated antigens (TAAs). Their capacity to stimulate the immune system has been suggested during late years. However, the role of the macrophages as key-elements in antigen-presentation process following TAAs-containing nanosystems is not completely understood. We aimed to evaluate the effect of gold nanoparticles functionalized with mucin-1 peptide (MUC-1) on murine peritoneal macrophages. Gold nanoparticles, obtained using a modified Turkevich method, were functionalized with MUC-1 protein using Clealand's reagent. The obtained GNP-MUC-1 solution was used to treat at various concentrations monolayers of peritoneum-derived macrophages that were further analyzed using confocal and hyperspectral microscopy, ELISA assays and spectroscopic techniques. The GNP-MUC-1 nano-construct had proven to function as a powerful macrophage activator with consequent release of cytokines such as: TNF-ɑ, IL-6, IL-10 and IL-12 on peritoneal macrophages we have isolated from mice. Our results demonstrate optimization of antigen-presenting process and predominant M1 polarization following exposure GNP-MUC-1. To our best knowledge this is the first study to evaluate the anticancer effects of a newly designed nano-biocompound on the complex antigen- processing apparatus of peritoneal macrophages.
Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.
Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289
Full Text Available Abstract Background Dendritic cells (DCs enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC. Methods We generated autologous DCs from the peripheral blood of HLA-A2+ patients with PC. DCs were pulsed with three distinct A2-restricted peptides: 1 human telomerase reverse transcriptase (hTERT, TERT572Y, 2 carcinoembryonic antigen (CEA; Cap1-6D, and 3 survivin (SRV.A2. Patients received four intradermal injections of 1 × 107 peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28, and 42. Concurrently, patients received intramuscular administration of Poly-ICLC at 30 μg/Kg on vaccination days (i.e., day 0, 14, 28, and 42, as well as on days 3, 17, 21, 31, 37, and 45. Our key objective was to assess safety and feasibility. The effect of DC vaccination on immune response was measured at each DC injection time point by enumerating the phenotype and function of patient T cells. Results Twelve patients underwent apheresis: nine patients with metastatic disease, and three patients with locally advanced unresectable disease. Vaccines were successfully manufactured from all individuals. We found that this treatment was well-tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms. Among the eight patients who underwent imaging on day 56, four patients experienced stable disease while four patients had disease progression. The median overall survival was 7.7 months. One patient survived for 28 months post leukapheresis. MHC class I –tetramer analysis before and after vaccination revealed effective generation of antigen-specific T cells in three patients with stable disease. Conclusion Vaccination with peptide-pulsed DCs in combination with poly-ICLC is safe and
Steigler, Pia; Daniels, Naomi J; McCulloch, Tim R; Ryder, Brin M; Sandford, Sarah K; Kirman, Joanna R
The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB; however, it fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to antimycobacterial immunity. To that end, innate cells may be involved in the protective response. In this study, we investigated the primary response of innate lymphoid cells (ILCs) to BCG exposure. Using a murine model, we showed that ILCs increased in number in the lungs and lymph nodes in response to BCG vaccination. Additionally, there was significant production of the antimycobacterial cytokine IFN-γ by ILCs. As ILCs are located at mucosal sites, it was investigated whether mucosal vaccination (intranasal) stimulated an enhanced response compared to the traditional vaccination approach (intradermal or subcutaneous). Indeed, in response to intranasal vaccination, the number of ILCs, and IFN-γ production in NK cells and ILC1s in the lungs and lymph nodes, were higher than that provoked through intradermal or subcutaneous vaccination. This work provides the first evidence that BCG vaccination activates ILCs, paving the way for future research to elucidate the protective potential of ILCs against mycobacterial infection. Additionally, the finding that lung ILCs respond rigorously to mucosal vaccination may have implications for the delivery of novel TB vaccines. © 2018 Australasian Society for Immunology Inc.
Raburn M Mallory
Full Text Available BACKGROUND: The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV were evaluated in children and adults. METHODS/PRINCIPAL FINDINGS: Two randomized, double-blind, placebo-controlled studies were completed in children (2-17 y and adults (18-49 y. Subjects were assigned 4:1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1-8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65 and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60 were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5% pediatric vaccine recipients and 1 (1.5% placebo recipient (rate difference, 0%; 95% CI: -6.4%, 3.1%. No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: -9.6%, 13.8% and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%. Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: -5.6%, 12.6% and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: -0.8%, 16.3% after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred. CONCLUSIONS/SIGNIFICANCE: In subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV. TRIAL REGISTRATION
González-Romo, Fernando; Picazo, Juan J
Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.
Yu, Qinghua; Zhu, Liqi; Kang, Haihong; Yang, Qian
Traditional non-gastrointestinal vaccines can prevent effectively the invasion of pathogens; however, these vaccines are less effective against mucosal infections because there is not a sufficient immune response at the mucosa. Most pathogens invade via a mucosal pathway (oral, intranasal, or vaginal). It is widely accepted that Lactobacillus species play a critical role as commensals in the gastrointestinal (GI) tract. Their ability to survive in the digestive tract, their close association with the intestinal epithelium, their immunomodulatory properties and their safety even when consumed in large amounts make lactobacilli attractive candidates for live vehicles for the delivery of immunogens to the intestinal mucosa. The oral or intranasal administration of Lactobacillus-based vaccines is a promising method to control mucosal infection because these vaccines could induce strong humoral and cellular immune responses both in the blood and at mucosal sites.
Liu, Heng; Frijlink, Henderik W.; Huckriede, Anke; van Doorn, Eva; Schmidt, Ed; Leroy, Odile; Rimmelzwaan, Guus; McCullough, Keneth; Whelan, Mike; Hak, Eelko
Due to influenza viruses continuously displaying antigenic variation, current seasonal influenza vaccines must be updated annually to include the latest predicted strains. Despite all the efforts put into vaccine strain selection, vaccine production, testing, and administration, the protective
Lee, Chan Wook
INTRODUCTION : The studies on allergic reaction with the substances of Ascaris lumbricoides have long been studied by various worers; Conventry(1929), Campbell(1936), Sakei(1949), Miyakawa(1950), Ikeda(1952), Matsumoto and Imawari(1952), Morishita and Kobayashi(1953, 1954), Komiyayama(1954) and Yammoto(1956). Campbell(1936) and some other workers reported that the polysaccharides from ascaris produced the stronger intrademal reactions than protein fraction, though Yamamoto(1954) and others found the reverse results. On the other hand, Hosotani(1954) reported that the crude antigen or mixed antigen with polysaccharide and protein fraction of the ascaris produced the strongest skin reaction than with the other single fraction. As are shown in above reports, the intensity of the allergic reaction with the substances from ascaris is still remained under dipute. The reason might be due to the difference of the method of preparation, technique and evaluation. The aim of the present study is to elucidate the intensity of allergic reactivity fo protein and polysaccharide fration and mixed substance of two fractions and crude antigen of Ascaris lumbricoides. MATERIALS AND METHODS : A Intrdermal Test 1. Human Experiment. The intradermal test was performed on several groups of people. A: Ascaris lumbricoides egg positive cases among adult ages. B: Ascaris lumbricoides egg negative cases but who bad doubtful symptom. C: Ascaris lumbricoides egg negative cases but who had past history of ascaris infection. D: Ascaris lumbricoides egg negative cases and aged 3-8 months old. 2. Animal Experiment: Same breeds of 6 dogs were raised i cages of laboratory for 6 months, During the period, special attention was paid to keep them in parasite free conditon. The body weight was 10kg in average. B. Antigens. The adults worms of Ascaris lumbricoides, which were obtained during laparotomy, were first washed with sterilized saline solution. Each ascaris was placed in 50ml of saline solution
Lorenzen, Niels; LaPatra, S.E.
Deoxyribonucleic acid (DNA) vaccination is based on the administration of the gene encoding the vaccine antigen, rather than the antigen itself. Subsequent expression of the antigen by cells in the vaccinated hosts triggers the host immune system. Among the many experimental DNA vaccines tested...... in various animal species as well as in humans, the vaccines against rhabdovirus diseases in fish have given some of the most promising results. A single intramuscular (IM) injection of microgram amounts of DNA induces rapid and long-lasting protection in farmed salmonids against economically important...... viruses such as infectious haematopoietic necrosis virus (IHNV) and viral haemorrhagic septicaemia virus (VHSV). DNA vaccines against other types of fish pathogens, however, have so far had limited success. The most efficient delivery route at present is IM injection, and suitable delivery strategies...
... HUMAN SERVICES 42 CFR Part 100 RIN 0907-AA National Vaccine Injury Compensation Program: Revisions to the Vaccine Injury Table AGENCY: Health Resources and Services Administration (HRSA), HHS. ACTION... information and views on the Notice of Proposed Rulemaking (NPRM) entitled ``National Vaccine Injury...
Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L
The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.
Roberts, D H; Lucas, M H; Wibberley, G; Chasey, D
The single intradermal comparative test was used with both avian and bovine tuberculin. Three cattle infected with bovine leukosis virus (BLV) were used as a source of infection. BLV-positive and susceptible animals were tuberculin tested alternately. Fifteen susceptible calves and 15 susceptible sheep were tested. A further three valves and three sheep were used as controls; the needles of the tuberculin syringes were deliberately contaminated with blood from the BLV-infected cattle, before being used in the test. Whereas all three calves and the three sheep inoculated intradermally with contaminated needles developed BLV infections, all of the other 30 animals have remained serologically negative to BLV for 10 months. Transmission of BLV with needles contaminated with BLV-infected blood was prevented by wiping the needles with absorbent cotton wool.
Sloet van Oldruitenborgh-Oosterbaan, Marianne M; van Poppel, Miriam; de Raat, Inge J; van den Boom, Robin; Savelkoul, Huub F J
Intradermal tests using a Culicoides nubeculosus extract have proven unreliable for diagnosis of equine insect bite hypersensitivity (IBH) in the Netherlands. The aim of this study was to evaluate the diagnostic value of an extract derived from the Dutch species C. obsoletus and C. pulicaris. Thirteen pairs of horses were tested, each pair consisting of one horse with IBH and the other a healthy control. Each horse was injected intradermally with 0.1 mL of three concentrations of Culicoides whole body extract (1 : 1000 w/v, 1 : 10,000 w/v and 1 : 25,000 w/v), histamine solution (0.01 mg/mL, positive control) and phosphate-buffered saline (negative control). Skin responses were evaluated after 30 min and at 1, 4 and 24 h. At all time points the absolute wheal diameter elicited by Culicoides extract 1 : 1000 w/v was significantly larger (P equine insect hypersensitivity.
... list . Showing availability for 25,354 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 ...
... are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common and serious health ... to 60 died. Since the introduction of the rotavirus vaccine, hospitalizations and emergency visits for rotavirus have dropped ...
Full Text Available Abstract Background Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. Results In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in
Magen, Eli; Mishal, Joseph; Zeldin, Yuri; Schlesinger, Menachem
Some patients with chronic idiopathic urticaria (CIU) are resistant to conventional doses of antihistamines (AHs). This study was designed to check whether the skin wheal and flare reaction produced by the intradermal injection of autologous serum (AS) and by histamine differs in AH-resistant and AH responder CIU patients. CIU patients with treatment failure under fexofenadine at 180 mg q.d. increased their daily dose of AH to 4 tablets daily. Those with significant improvement of urticaria activity score under fexofenadine at 180 mg were included in the CIU group. Subjects with treatment failure despite a full 8-week fourfold fexofenadine treatment were included in the resistant CIU (R-CIU group). The control group consisted of sex- and age-matched patents with allergic rhinitis. The AS skin test and intradermal histamine-induced wheal and flare reaction were performed at baseline (without AH), after 8 and 16 weeks (under AH treatment). Forty-six subjects were included in the CIU group, 21 were in the R-CIU group, and 44 were in the control group. Under AH therapy, the skin reaction to intradermal histamine injection was significantly diminished in all study groups. In the R-CIU group, fexofenadine at 180 mg did not suppress AS-induced wheal reaction (5.96 ± 2.25 mm; p = 0.85), and with a fourfold AH dose some reduction of AS-induced wheal (3.79 ± 1.74 mm; p = 0.008) was observed but remained larger than in the CIU (2.31 ± 1.12; p = 0.006) and control groups (2.52 ± 1.36; p = 0.037). AHs do not inhibit the wheal induced by the intradermal injection of AS in R-CIU.
Marques, Ana Paula da C; Oliveira, Sandra Maria V L; Rezende, Grazielli R; Melo, Dayane A; Fernandes-Fitts, Sonia M; Pontes, Elenir Rose J C; Bonecini-Almeida, Maria da Glória; Camargo, Zoilo P; Paniago, Anamaria M M
Epidemiological studies of paracoccidioidomycosis have been based on surveys achieved with intradermal tests, and paracoccidioidin is the most common antigen used in most cases. The glycoprotein of 43-kDa (gp43) has been used in intradermal tests. It is the most antigenic component of Paracoccidioides brasiliensis, and it provides greater specificity to evaluate infection for this fungus. In this study, the prevalence of P. brasiliensis infection was estimated with intradermal tests involving gp43 for 695 people in rural Central-West Brazil. The infection rate was 45.8 % (95 % CI = 42.1-49.5), and the average age of those infected was 45.8 ± 18.2 years. The prevalence did not show gender-based differences but increased with age. The results demonstrate the importance of P. brasiliensis infection in rural settlements and the early exposure of children in the region to the fungus. Despite the high antigenicity and specificity of gp43, its usage must be standardized, so that epidemiological surveys will be comparable and more accurately reflect P. brasiliensis infection in endemic areas.
Yuen, Clement; Liu, Quan
Human intradermal components contain important clinical information beneficial to the field of immunology and disease diagnosis. Although microneedles have shown great potential to act as probes to break the human skin barrier for the minimally invasive measurement of intradermal components, metal microneedles that include stainless steel could cause the following problems: (1) sharp waste production, and (2) contamination due to reuse of microneedles especially in developing regions. In this study, we fabricate agarose microneedles coated with a layer of silver (Ag) and demonstrate their use as a probe for the realization of intradermal surface-enhanced Raman scattering measurements in a set of skin-mimicking phantoms. The Ag-coated agarose microneedle quantifies a range of glucose concentrations from 5 to 150 mM inside the skin phantoms with a root-mean-square error of 5.1 mM within 10 s. The needle is found enlarged by 53.9% after another 6 min inside the phantom. The shape-changing capability of this agarose microneedle ensures that the reuse of these microneedles is impossible, thus avoiding sharp waste production and preventing needle contamination, which shows the great potential for safe and effective needle-based measurements.
International Conference on Harmonisation; Electronic Transmission of Postmarket Individual Case Safety Reports for Drugs and Biologics, Excluding Vaccines; Availability of Food and Drug Administration Regional Implementation Specifications for ICH E2B(R3) Reporting to the Food and Drug Administration Adverse Event Reporting System. Notice of Availability.
The Food and Drug Administration (FDA) is announcing the availability of its FDA Adverse Event Reporting System (FAERS) Regional Implementation Specifications for the International Conference on Harmonisation (ICH) E2B(R3) Specification. FDA is making this technical specifications document available to assist interested parties in electronically submitting individual case safety reports (ICSRs) (and ICSR attachments) to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). This document, entitled "FDA Regional Implementation Specifications for ICH E2B(R3) Implementation: Postmarket Submission of Individual Case Safety Reports (ICSRs) for Drugs and Biologics, Excluding Vaccines" supplements the "E2B(R3) Electronic Transmission of Individual Case Safety Reports (ICSRs) Implementation Guide--Data Elements and Message Specification" final guidance for industry and describes FDA's technical approach for receiving ICSRs, for incorporating regionally controlled terminology, and for adding region-specific data elements when reporting to FAERS.
Conforti, Giorgio; Capone, Loredana; Corra, Stefano
The carpal tunnel syndrome (CTS) is the most common cause of severe hand pain. In this study we treated acute pain in CTS patients by means of local intradermal injections of anti-inflammatory drugs (mesotherapy). In twenty-five patients (forty-five hands), CTS diagnosis was confirmed by clinical and neurophysiological examination prior to mesotherapy. A mixture containing lidocaine 10 mg, ketoprophen lysine-acetylsalycilate 80 mg, xantinol nicotinate 100 mg, cyanocobalamine 1,000 mcg plus injectable water was used. Sites of injection were three parallel lines above the transverse carpal ligament and two v-shaped lines, one at the base of the thenar eminence, and the other at the base of the hypothenar eminence. The day after the treatment, all but four patients reported a significant reduction in pain and paresthesias. After 12 months, 17 patients had a complete pain relief, eight patients reported recurrence of pain and sensory symptoms and four out of them underwent surgical treatment. With the obvious limits of a small-size open-label study, our results suggest that mesotherapy can temporary relieve pain and paresthesias in most CTS patients and in some cases its effect seems to be long-lasting. Further controlled studies are needed to confirm our preliminary findings and to compare mesotherapy to conventional approaches for the treatment of CTS.
Amatya, B; Nordlind, K; Wahlgren, C-F
Various mediators have been suggested for the pathogenesis of pruritus in psoriasis. To investigate cutaneous responses of substance P in pruritic lesional and nonlesional areas of psoriasis patients and in healthy controls, substance P, saline and histamine were injected intradermally. After each injection, pruritus, flare and wheal were recorded. There was no statistical difference in the latency period, duration, area under the curve and maximum intensity of pruritus evoked by substance P (10(-5) and 10(-6) mol/l) between psoriasis and healthy control skin. Substance P (10(-5) mol/l) induced a tendency to a greater intensity of pruritus in lesional compared to nonlesional psoriatic skin (p = 0.08). Histamine produced a shorter itch latency period (p skin than in healthy control skin. No significant difference in flare area was observed between the psoriasis patients and healthy controls. The histamine-induced wheal was smaller in psoriasis patients than in healthy individuals (p wheal in psoriasis patients. However, these responses did not differ significantly from those of the healthy controls. Copyright 2009 S. Karger AG, Basel.
Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj; Wynn, Thomas A; Madala, Satish K
IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.
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
Christopher J Greene
Full Text Available Currently, there is a shortage of adjuvants that can be employed with protein subunit vaccines to enhance protection against biological threats. LT-IIb(T13I is an engineered nontoxic derivative of LT-IIb, a member of the type II subfamily of heat labile enterotoxins expressed by Escherichia coli, that possesses potent mucosal adjuvant properties. In this study we evaluated the capacity of LT-IIb(T13I to augment the potency of RiVax, a recombinant ricin toxin A subunit vaccine, when co-administered to mice via the intradermal (i.d. and intranasal (i.n. routes. We report that co-administration of RiVax with LT-IIb(T13I by the i.d. route enhanced the levels of RiVax-specific serum IgG antibodies (Ab and elevated the ratio of ricin-neutralizing to non-neutralizing Ab, as compared to RiVax alone. Protection against a lethal ricin challenge was also augmented by LT-IIb(T13I. While local inflammatory responses elicited by LT-IIb(T13I were comparable to those elicited by aluminum salts (Imject®, LT-IIb(T13I was more effective than aluminum salts at augmenting production of RiVax-specific serum IgG. Finally, i.n. administration of RiVax with LT-IIb(T13I also increased levels of RiVax-specific serum and mucosal Ab and enhanced protection against ricin challenge. Collectively, these data highlight the potential of LT-IIb(T13I as an effective next-generation i.d., or possibly i.n. adjuvant for enhancing the immunogenicity of subunit vaccines for biodefense.
Gerber, Jeffrey S.; Offit, Paul A.
Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms ...
Guthmann, J P; Antoine, D; Fonteneau, L; Che, D; Lévy-Bruhl, D
We report data on BCG vaccination coverage and paediatric tuberculosis (TB) incidence collected after the disappearance of the multipuncture device for BCG vaccination in January 2006 and the shift from universal to targeted vaccination in July 2007 in France.Vaccination coverage estimates in children for whom BCG is recommended allow assessing whether the recommendations are followed by doctors and/or accepted by the target population. In January and February 2006, BCG sales to the private sector in Îlede-France region were 74.2% and 41.3% of the ones for the same months the previous year. Total sales in 2006 amounted to 57.3% of those in 2005. Coverage decreased immediately after withdrawal of the multipuncture device, and remained generally insufficient in high risk children in the following years. However,the impact on paediatric TB incidence in 2008 seems very limited, although the duration of follow-up is still short. Training of doctors in intra-dermal vaccination and communication on the new vaccination policy should be strengthened
I. V. Konovalov
Full Text Available We estimated the safety of the vaccination for prevention of influenza with Grippol® plus vaccine alongside with vaccination with combined preparations for the prevention of diphtheria and tetanus (Td and measles, rubella, mumps in children aged 6—7 years. We determined that combined immunization with the indicated vaccines proves good tolerability and low reactogenicity. Vaccine Grippol® Plus shows low reactogenicity , high immunologenicity and does not cause cross-suppression of antibodies in co-administration with other vaccines on vaccination calendar. Also concomitant vaccination with Grippol® plus and other vaccines does not inhibit the development of a specific immune response against influenza.
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
Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.
The past few years have seen important developments in understanding the epidemiological and virological characteristics of rotaviruses, and rapid progress has been made in rotavirus vaccine development, but further challenges remain before a vaccine is introduced into widespread use. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. The association between the tetravalent rhesus-based rotavirus vaccine and intussusception has created significant hurdles as well as new opportunities to study the pathogenesis of rotavirus and rotavirus vaccine infection. Several other rotavirus vaccine candidates are in late stages of development, and results from trials have been encouraging.
Rowland, Michael; Plackett, Timothy P; Smith, Richard
Yellow fever is a mosquito-transmitted hemorrhagic viral disease that is endemic to tropical regions in South America and Africa. It remains a significant health concern for deploying military personnel, accordingly vaccination is frequently performed on troops. Although the vaccine is generally administered with only minor complications, rare severe complications are also reported. Herein, we report a mild case of yellow fever vaccine-associated viscerotropic disease 4 days after administration of the vaccine. The various complications of the vaccine and their pathogenesis are also reviewed.
Tebas, Pablo; Roberts, Christine C; Muthumani, Kar; Reuschel, Emma; White, Scott; Khan, Amir S; Racine, Trina; Choi, Hyeree; Zaidi, Faraz; Boyer, Jean; Kudchodkar, Sagar; Park, Young K; Trottier, Sylvie; Remigio, Celine; Krieger, Diane; Kobinger, Gary P; Weiner, David; Maslow, Joel
Abstract Background While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. Methods ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA®-3P device Results The median age of the 40 participants was 38 (IQR 30–54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea. Four weeks after the first dose 25% vs. 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose, the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 106 PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived
Seok, Hae-yong; Suh, Hyemee; Baek, Sunghyun; Kim, Yeu-Chun
Microneedles were initially developed as pretreatment tools for the delivery of therapeutic drugs to intradermal locales in the human skin. Over time, variations in microneedle forms and functions burgeoned through the works of many researchers worldwide. The four major types of microneedles in use today are solid, dissolving, coating, and hollow microneedles. The emergence of different types of microneedles also paved the way for a flourishing diversification of microneedle applications, one of the most remarkable of which deals with the transcutaneous delivery of prophylactic vaccines. Here, we describe fabrication methods of microneedles and DNA vaccine loading methods on the microneedle surface. Furthermore, in the latter part of this chapter, in vivo test protocols for assessing the efficacy of gene delivery using microneedles are described.
Nishizawa, Toyohiko; Takami, Ikuo; Yang, Minji; Oh, Myung-Joo
The process of "Poly(I:C) immunization" involves immunization of fish with a pathogenic live virus, followed by administration of Poly(I:C), which induces a transient, non-specific antiviral state. As a result, fish in an antiviral state survive the initial immunization with live virus. Moreover, these fish are able to mount a specific protective immune response against the injected pathogenic virus. In the present study, we investigated the optimum temperature for Poly(I:C) immunization of Japanese flounder Paralichthys olivaceus with live viral hemorrhagic septicemia virus (VHSV). It was revealed that the optimum temperature was around at 17°C for Poly(I:C) immunization in Japanese flounder. Furthermore, the protection efficacy of Poly(I:C) immunization was significantly decreased by elevation of fish rearing temperature, and no efficacy was observed at a fish rearing temperature of 25°C. Interestingly, no mortality by VHSV infection was observed in fish reared at 21°C and 25°C even when those fish were not administered Poly(I:C). All of the survivors from the first VHSV-challenge at 21°C were strongly protected from re-challenge with VHSV. However, almost all of the survivors (≥82.6%) from the first challenge at 25°C were lost by the second challenge with VHSV. It was thus concluded that by rearing fish at 21°C and challenging with live VHSV, it is possible to induce strong specific immunity in Japanese flounder without Poly(I:C) administration. Copyright © 2011 Elsevier Ltd. All rights reserved.
A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers.
Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion
As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092.
Ohri, Linda K
There has been substantial media coverage of the quadrivalent human papillomavirus (HPV) vaccine since the Food and Drug Administration approved Gardasil (Merck & Co., Inc.) on June 8, 2006. The most vocal complaints maintain that its use will promote promiscuity among teenagers, and condemn proposed mandated use for school entry. Some also question evidence for the vaccine's safety. There have been concerns raised by both providers and patients regarding financial barriers to access. Still others argue that additional populations could benefit who have not been included in current recommendations. Clarification of these issues is essential to advance optimal use of this important new vaccine. There is strong evidence to support HPV vaccine as an effective, safe, and efficient public health measure. School mandates are valuable tools to reduce disparities in availability of immunizations. The time has come to consider universal funding as a means to improve access to all recommended vaccines.
Full Text Available Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d. inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11-12 days post-infection (dpi, followed by marked hypothermia and body weight loss at 14-19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF, as well as modulatory cytokines (IL-9, IL-13. Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions.
Aliabadi, N; Tate, J E; Parashar, U D
Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally. Published by Elsevier Ltd.
Guarino, Cassandra; Asbie, Sanda; Rohde, Jennifer; Glaser, Amy; Wagner, Bettina
Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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
CERN Medical Service
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
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
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
... influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT be ... What is live, attenuated influenza vaccine-LAIV (nasal spray)?A dose of flu vaccine is recommended every flu season. Children younger ...
Full Text Available Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E fused to the T4 fibritin foldon trimerization domain (Efl. The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA. The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%. No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.
Kim, Eun; Erdos, Geza; Huang, Shaohua; Kenniston, Thomas; Falo, Louis D; Gambotto, Andrea
Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease. Copyright Â© 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Full Text Available Background: Considering the dramatic increasing rate of diabetes and consequently its related complications, most importantly diabetic peripheral neuropathy (DPN, challenges regarding proper treatment of DPN and its effect on the quality-of-life and care of diabetic patients, the aim of this current study is to evaluate the effect of intradermal botulinum toxin type A (BTX-A injections on pain symptoms of patients with diabetic neuropathic pain. Materials and Methods: In this randomized double-blind placebo-controlled clinical trial study, diabetic patients aged <70 years with neuropathic pain in both feet were enrolled. Diabetic neuropathy (DN in selected patients was diagnosed using DN4 questionnaire and nerve conduction velocity examinations. They randomized in two intervention (BTX-A injection/100 unit, N = 20 and placebo groups (normal saline injection, N = 20. The outcome of injection on diabetic neuropathic pain was assessed using neuropathy pain scale (NPS and visual analog scale (VAS score and compared in two studied groups. Results: There was no significant difference in DN4, NPS and VAS scales of studied population after intervention in the placebo group. Intradermal injection of BTX-A reduced NPS scores for all items except cold sensation (P = 0.05. It reduced DN4 scores for electric shocks, burning, pins and needles and brushing (P < 0.05. According to VAS scale 30% and 0% of patients in intervention and placebo groups have no pain after intervention (P = 0.01. Conclusion: Intradermal injection of BTX-A is a well-tolerated agent that has a significant effect on DPN pain.
A solid tumor related to viral infection is a rare and challenging condition to the medical community raising the possibility to fight and prevent this cancer by vaccine. Cervical cancer, caused by human papillomavirus (HPV), is a major health problem worldwide. The two HPV vaccines approved lately could lead to more than a 70% reduction in cases of cervical cancer and a similar reduction in deaths from the cancer. Pap smear screening significantly (80%) reduced disease incidence and is still useful and needed. In addition to early detection, vaccination will prevent the development of precancerous and cancerous lesion and reduce morbidity, mortality and psychological and social stress as well as stressful and expensive follow-ups in women with suspicious lesions. The vaccinations described will bring to a significant reduction in genital warts incidence, a serious social and psychological burden to the infected population. Practical social and psychological issues are still to be addressed, some of them are: time and frequency of administration, use of vaccination in men, public acceptance and behavior, appropriate populations to be vaccinated, etc. Most unresolved questions will be answered over time. The new vaccines embody a big promise to humanity, although we still have to overcome the financial burden and possible late side effects of the vaccine.
Gershwin, Laurel J; Netherwood, Kristina A; Norris, Meredith Somerville; Behrens, Nicole E; Shao, Matt X
Vaccination of horses is performed annually or semi-annually with multiple viral antigens, either in a combination vaccine or as separate injections. While this practice undoubtedly prevents infection from such diseases as rabies, equine influenza, West Nile virus, and equine herpes virus, the procedure is not without repercussions. Hypersensitivity reactions, including fatal anaphylactic shock, after vaccination, although uncommon, have increased in incidence in recent years. Studies reported herein document the development of IgE antibodies against non-target antigen components of equine viral vaccines. We hypothesize that viral vaccines can induce an IgE response to non-target antigens, which could elicit an adverse response after vaccination with another viral vaccine containing the same component. In one study IgE responses to components of West Nile virus vaccine were evaluated by ELISA before and after vaccination in 30 horses. In a second five-year study 77 horses were similarly tested for IgE antibodies against bovine serum albumin (BSA), a component of most viral vaccines. Mast cell sensitization was evaluated in horses with high, moderate, and negative serum BSA specific IgE using an intradermal skin test with BSA. Over the five-year period high IgE responder horses showed gradually increasing BSA specific serum IgE levels and positive skin test reactivity, yet none had an adverse event. Sera from horses that had developed adverse vaccine reactions were also tested for IgE antibodies. Several of these horses had extremely high levels of BSA-specific IgE. These data suggest that non-essential protein components of vaccines may sensitize horses for future adverse responses to vaccination. Copyright © 2012 Elsevier Ltd. All rights reserved.
Andersen, Susanne A; Petersen, Henrik H; Ersbøll, Annette K; Falk-Rønne, Jørgen; Jacobsen, Stine
European and American guidelines for vaccination against tetanus and influenza in horses recommend annual and annual/semi-annual vaccinations, respectively, against the two pathogens. Too-frequent vaccination may, however, have adverse effects, among other things because an inflammatory response is elicited with subsequent alterations in homeostasis. The objective of the study was to compare the acute phase response (APR) in 10 horses following administration of two different types of vaccines, namely, an inactivated Immune Stimulating COMplex (ISCOM) vaccine and a live recombinant vector vaccine. Blood was sampled before and after vaccination to measure levels of serum amyloid A (SAA), fibrinogen, white blood cell counts (WBC) and iron. Vaccination induced a prominent APR with increased WBC, elevated blood levels of SAA and fibrinogen, and decreased serum iron concentrations. The ISCOM vaccine caused significantly (Phorse owners about convalescence after vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.
de Vries, Rory D; Stittelaar, Koert J; Osterhaus, Albert D M E; de Swart, Rik L
Measles is a highly contagious viral disease. With 1 million deaths reported in 1996, measles was the leading cause of vaccine-preventable deaths. However, in recent years, significant progress has been made in measles control, reducing deaths attributed to measles to 454,000 in 2004 and 242,000 in 2006. The main strategy behind this reduction has been the improvement of vaccination coverage and implementation of a second opportunity for immunization with the live-attenuated measles vaccine. The Measles Initiative, a partnership between the American Red Cross, CDC, UNICEF, WHO and UN Foundation, has had a significant role in this achievement. Here, we provide an overview of old and new vaccination strategies, and discuss changes in the route of administration of the existing live-attenuated vaccine, the development of new-generation nonreplicating measles virus vaccine candidates and attempts to use recombinant measles virus as a vector for vaccination against other pathogens.
van Zwol, Ulla Bonde; Joergensen, J. S.; Lamont, R. F.
Millions of doses of HPV vaccine have been administered globally. Inadvertent administration of HPV vaccine during pregnancy occurs given that the main recipients of the vaccine are fertile young women, who might be unaware of their pregnancy at the time of their vaccination. To investigate...... the subject of HPV vaccine and pregnancy , the databases of PubMed and Embase were searched to find the relevant literature published in English within the last 10 y. Most of the evidence pertaining to fetal adverse events following HPV vaccination relates to spontaneous miscarriage. None of the relevant...... studies found any significantly increased rate of spontaneous abortion in the overall analyses. There was no indication of other HPV vaccine-associated adverse events in pregnancy or immediately post-conception. © 2016 Taylor & Francis....
Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant
Bezos, J; Casal, C; Álvarez, J; Roy, A; Romero, B; Rodríguez-Bertos, A; Bárcena, C; Díez, A; Juste, R; Gortázar, C; Puentes, E; Aguiló, N; Martín, C; de Juan, L; Domínguez, L
The development of new vaccines against animal tuberculosis (TB) is a priority for improving the control and eradication of this disease, particularly in those species not subjected to compulsory eradication programmes. In this study, the protection conferred by the Mycobacterium tuberculosis SO2 experimental vaccine was evaluated using a natural infection model in goats. Twenty-six goats were distributed in three groups: (1) 10 goats served as a control group; (2) six goats were subcutaneously vaccinated with BCG; and (3) 10 goats were subcutaneously vaccinated with SO2. Four months after vaccination, all groups were merged with goats infected with Mycobacterium bovis or Mycobacterium caprae, and tested over a 40 week period using a tuberculin intradermal test and an interferon-γ assay for mycobacterial reactivity. The severity of lesions was determined at post-mortem examination and the bacterial load in tissues were evaluated by culture. The two vaccinated groups had significantly lower lesion and bacterial culture scores than the control group (P<0.05); at the end of the study, the SO2 vaccinated goats had the lowest lesion and culture scores. These results suggest that the SO2 vaccine provides some protection against TB infection acquired from natural exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.
Chen, Xinyuan; Kositratna, Garuna; Zhou, Chang; Manstein, Dieter; Wu, Mei X
Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1h. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and at least sustained immunogenicity. Copyright © 2014 Elsevier B.V. All rights reserved.
... foreign. Most preventive vaccines, including those aimed at cancer-causing viruses ( hepatitis B virus and human papillomavirus ), stimulate the ... 9 through 25 for the prevention of cervical cancer caused by HPV. Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to ...
Tran, Vanessa; Liu, Jun; Behr, Marcel A
BCG is the collective name for a family of live attenuated strains of Mycobacterium bovis that are currently used as the only vaccine against tuberculosis (TB). There are two major reasons for studying the genome of these organisms: (i) Because they are attenuated, BCG vaccines provide a window into Mycobacterium tuberculosis virulence, and (ii) because they have provided protection in several clinical trials and case-control studies, BCG vaccines may shed light on properties required of a TB vaccine. Since the determination of the M. tuberculosis genome in 1998, the study of BCG vaccines has accelerated dramatically, offering data on the genomic differences between virulent M. tuberculosis, M. bovis, and the vaccine strains. While these findings have been rewarding for the study of virulence, there is unfortunately less accrued knowledge about protection. In this chapter, we review briefly the history of BCG vaccines and then touch upon studies over the past two decades that help explain how BCG underwent attenuation, concluding with some more speculative comments as to how these vaccines might offer protection against TB.
Full Text Available Thyme is a herb with effects on the respiratory system. The aim of the current study was to investigate the effects of thyme essence on trachea, humoral immunity, and the performance of broilers following LaSota vaccination. In this study, 300 Ross 308 broiler chicks were divided into 3 groups of 100 chicken. The first group received 50 ppm thyme essence 2 days prior to and after LaSota vaccination. In the second group only LaSota vaccine was used, and in the third group B1 vaccine was used to compare its severity to the LaSota vaccine. Finally at the end of production period (42 days samples were taken from trachea for histopathology and also titer of Newcastle vaccine and the performance of chicks were investigated. Results of this study showed that thyme essence decreased histopathologic changes due to vaccination reaction in the trachea. Histopathologic alteration was not observed in B1 vaccination group. In view of feed conversion ratio, feed consumption and final body weight in thyme group there was significant improvement in comparison to LaSota group (p
Inactivated influenza vaccine adjuvanted with Bacterium-like particles induce systemic and mucosal influenza A virus specific T-cell and B-cell responses after nasal administration in a TLR2 dependent fashion
Keijzer, C.; Haijema, B. J.; Meijerhof, T.; Voorn, P.; de Haan, A.; Leenhouts, K.; van Roosmalen, M. L.; van Eden, W.; Broere, F.
Background: Nasal vaccination is considered to be a promising alternative for parenteral vaccination against influenza virus as it is non-invasive and offers the opportunity to elicit strong antigen-specific responses both systemic and locally at the port of entry of the pathogen. Previous studies
No significant differences in the breadth of the foot-and-mouth disease serotype A vaccine induced antibody responses in cattle, using different antigens, mixed antigens and different toutes of administration
Tekleghiorghis, T.; Weerdmeester, K.; Hemert-Kluitenberg, F.; Moormann, R.J.M.; Dekker, A.
Inactivated whole virus foot-and-mouth disease (FMD) vaccines are used worldwide for protection against FMD, but not all vaccines induce protection against all genetic variants of the same FMD virus serotype. The aim of this study is to investigate whether the “breadth” of the antibody response
David AG Skibinski
Full Text Available 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 these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.
Van Nuffel, An M T; Benteyn, Daphné; Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; Neyns, Bart; Thielemans, Kris; Bonehill, Aude
Dendritic cells (DCs) electroporated with mRNA encoding CD70, CD40L and a constitutively active toll-like receptor 4 (TriMix-DC) have an increased T-cell stimulatory capacity. In a prospective phase IB clinical trial, we treated melanoma patients with intradermal and intravenous injections of autologous TriMix-DC co-electroporated with mRNA encoding full-length MAGE-A3, MAGE-C2, tyrosinase and gp100. We report here the immunological and clinical results obtained in one patient with a particularly favorable outcome. This patient had stage IV-M1c melanoma with documented progression during dacarbazine chemotherapy and received 5 TriMix-DC injections. Following DC therapy, a broad CD8(+) T-cell response against multiple epitopes derived from all four treatment antigens was found in the blood and among T cells derived from DTH biopsy. In addition, CD4(+) T cells recognizing different MAGE-A3-derived epitopes were detected in DTH-derived cells. A spontaneous anti-MAGE-C2 CD8(+) T-cell response was present prior to TriMix-DC therapy and increased during treatment. The tumor response was assessed with 18-fluorodeoxyglucose-positron emission/computed tomography. We documented a partial tumor response according to RECIST criteria with a marked reduction in (18)F-FDG-uptake by lung, lymph node and bone metastases. The patient remains free from progression after 12 months of follow-up. This case report indicates that administration of autologous TriMix-DC by the combined intradermal and intravenous route can mediate a durable objective tumor response accompanied by a broad T-cell response in a chemorefractory stage IV-M1c melanoma patient.
Dillenberg, H.; Waldron, M. P. D.
In a controlled study, Greenberg's staphylococcal polyvalent somatic antigen vaccine was administered to 190 Indian volunteers of a reserve in Saskatchewan in an attempt to reduce the incidence of impetigo. An intradermal skin test dose of 0.1 ml. was given initially. Reactors were forthwith placed in a separate category, otherwise this test injection was followed by intramuscular injection of 0.25 ml. of the vaccine, repeated a second time after six weeks. One hundred and sixty-nine controls received “placebo vaccine”. Four months later the number of cases of impetigo in the vaccinated group had been reduced from 55 to 16. There was no reduction in the control group. The preventive effect waned after five months. The results of this field trial are considered encouraging. PMID:14052980
Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie
OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... and 2133 randomised (73 premature) to the control group. INTERVENTIONS: BCG vaccination 0.05 ml was given intradermally in the upper left arm at the hospital within seven days of birth. Children in the control group did not receive any intervention. Parents were not blinded to allocation. MAIN OUTCOME...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....
Bragstad, Karoline; Vinner, Lasse; Hansen, Mette Sif
The composition of current influenza protein vaccines has to be reconsidered every season to match the circulating influenza viruses, continuously changing antigenicity. Thus, influenza vaccines inducing a broad cross-reactive immune response would be a great advantage for protection against both...... seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs...... intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA...
Background: Improper handling has been identified as one of the major reasons for the decline in vaccine potency at the time of administration. Loss of potency becomes evident when immunised individuals contract the diseases the vaccines were meant to prevent. Objective: Assessing the factors associated with vaccine ...
Guthmann, J-P; Fonteneau, L; Desplanques, L; Lévy-Bruhl, D
Compulsory BCG vaccination was replaced in July 2007 by a strong recommendation to vaccinate children at high risk of tuberculosis. We measured BCG vaccination coverage (VC) in children for whom BCG is recommended, who were born after the end of compulsory BCG vaccination and are usually followed at Maternal and Child Health Clinics (MCHC). National sampling survey stratified by region and age group. Sample size was calculated in order to perform a separate analysis in Ile-de-France, region which has a specific vaccination policy and the highest tuberculosis incidence in mainland France. Children were selected through 2-stage random sampling in IDF and 3-stage random sampling outside IDF. They were recruited at the MCHC during the consultation where information was collected by the doctor through a structured questionnaire. BCG-VC was 89.8% (81.4-94.7) in IDF and 61.7% (53.8-69.0) outside IDF. In IDF, VC in children who had other criteria than solely residing in IDF was 92.4%. Outside IDF, children were on average vaccinated later than in IDF (i.e.: VC at the age of 3 months in children aged 2-12 months: 84% in IDF, 42% outside IDF). In both zones, children aged 2-12 months were vaccinated earlier compared to those aged >12 months. VC are high in children followed at MCHC in IDF, but can still be improved. They are insufficient in those followed at MCHC outside IDF where children are vaccinated too late. Efforts aimed at improving the dissemination of BCG vaccination recommendations and a better training of doctors in performing intradermal BCG vaccination could facilitate the implementation of this new BCG vaccination policy. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Maggiori, Enrica; Bartoletti, Emanuele; Mammucari, Massimo
Chronic venous insufficiency (CVI) induces alterations that cause fibrosclerotic edema of the subcutaneous tissue. This study examined the effects of a complex naturopathic compound with vasoactive and antiedema activities (Lymdiaral®) administered intradermally. 40 patients with signs and symptoms of CVI and associated fibrosclerotic edema of the subcutaneous tissue. Efficacy was assessed by using clinical investigation, subjective and objective measures, and ultrasonography performed at baseline and after treatment. Thirty-four patients completed the study; 6 of the original 40 (15%) had stopped for reasons unrelated to study treatment. The treatment was well tolerated. Fifteen adverse reactions were reported among a total of 378 doses administered (3.97%). None of these reactions were severe or required discontinuation of treatment. Subjective symptoms and objective measures improved, and ultrasonography showed statistically significant changes in hypodermal thickness of the medial aspect of the knees. Its open-label design and small sample size notwithstanding, this study indicates that intradermal therapy, according to the recommendation of the Italian Society of Mesotherapy, may provide a valuable contribution to the treatment of CVI and related fibrosclerotic edema of the subcutaneous tissue by prolonging the local effect of the pharmacologically active compounds. Comparative studies are needed to identify the broader clinical and economic benefits of local therapy compared with other systemic therapies.
Alves, Renato V.; Brandão,Fabiano H.; Aquino,José E. P.; Carvalho,Maria R. M. S.; Suzana M. Giancoli; Younes,Eduado A. P.
Muito comuns, os nevos intradérmicos constituem um tumor cutâneo pigmentado benigno. Seu aparecimento no meato auditivo externo é inabitual. Os aspectos clínicos e histopatológicos dos nevos intradérmicos dentro do meato auditivo externo são apresentados e a literatura é revisada.Intradermal nevi are common benign pigmented skin tumors. Their occurrence within the external auditory canal is uncommon. The clinical and pathologic features of an intradermal nevus arising within the external audi...
Renato V. Alves
Full Text Available Muito comuns, os nevos intradérmicos constituem um tumor cutâneo pigmentado benigno. Seu aparecimento no meato auditivo externo é inabitual. Os aspectos clínicos e histopatológicos dos nevos intradérmicos dentro do meato auditivo externo são apresentados e a literatura é revisada.Intradermal nevi are common benign pigmented skin tumors. Their occurrence within the external auditory canal is uncommon. The clinical and pathologic features of an intradermal nevus arising within the external auditory canal are presented, and the literature reviewed.
... Educators Search English Español Your Child's Immunizations: Meningococcal Vaccines KidsHealth / For Parents / Your Child's Immunizations: Meningococcal Vaccines Print The meningococcal vaccines protect ...
Kirkpatrick, Beth D.; Durbin, Anna P.; Pierce, Kristen K.; Carmolli, Marya P.; Tibery, Cecilia M.; Grier, Palmtama L.; Hynes, Noreen; Diehl, Sean A.; Elwood, Dan; Jarvis, Adrienne P.; Sabundayo, Beulah P.; Lyon, Caroline E.; Larsson, Catherine J.; Jo, Matthew; Lovchik, Janece M.; Luke, Catherine J.; Walsh, Mary C.; Fraser, Ellen A.; Subbarao, Kanta; Whitehead, Steven S.
Background. The 4 serotypes of dengue virus, DENV-1–4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods. Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results. A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions. A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic. Clinical Trials Registration. NCT01072786 and NCT01436422. PMID:25801652
Nachbagauer, R; Krammer, F
Current influenza virus vaccines are effective when well matched to the circulating strains. Unfortunately, antigenic drift and the high diversity of potential emerging zoonotic and pandemic viruses make it difficult to select the right strains for vaccine production. This problem causes vaccine mismatches, which lead to sharp drops in vaccine effectiveness and long response times to manufacture matched vaccines in case of novel pandemic viruses. To provide an overview of universal influenza virus vaccines and therapeutic antibodies in preclinical and clinical development. PubMed and clinicaltrials.gov were used as sources for this review. Universal influenza virus vaccines that target conserved regions of the influenza virus including the haemagglutinin stalk domain, the ectodomain of the M2 ion channel or the internal matrix and nucleoproteins are in late preclinical and clinical development. These vaccines could confer broad protection against all influenza A and B viruses including drift variants and thereby abolish the need for annual re-formulation and re-administration of influenza virus vaccines. In addition, these novel vaccines would enhance preparedness against emerging influenza virus pandemics. Finally, novel therapeutic antibodies against the same conserved targets are in clinical development and could become valuable tools in the fight against influenza virus infection. Both universal influenza virus vaccines and therapeutic antibodies are potential future options for the control of human influenza infections. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Dahiya, Shyam S; Saini, Mohini; Kumar, Pankaj; Gupta, Praveen K
A replicon-based DNA vaccine encoding VP2 gene of canine parvovirus (CPV) was developed by cloning CPV-VP2 gene into a replicon-based DNA vaccine vector (pAlpha). The characteristics of a replicon-based DNA vaccine like, self-amplification of transcripts and induction of apoptosis were analyzed in transfected mammalian cells. When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. The virus neutralization antibody and lymphocyte proliferative responses were higher than conventional CPV DNA vaccine and commercial CPV vaccine. These results indicated that DNA-launched replicon-based CPV DNA vaccine was effective in inducing both CPV-specific humoral and cellular immune responses and can be considered as effective alternative to conventional CPV DNA vaccine and commercial CPV vaccine. Crown Copyright © 2012. Published by Elsevier India Pvt Ltd. All rights reserved.
The impact of avian influenza on poultry production is undeniable. Field outbreaks of H5N1 HPAI have occurred in vaccinated flocks from both failure of the vaccines (i.e. vaccine efficacy) and failure in administration or immune response of the target species (i.e. vaccination effectiveness). Antige...
Background: The burden of tuberculosis is high in Nigeria as in other developing countries. The administration of BCG vaccine to neonates is essential in the control of tuberculosis. A scar usually develops 6 – 8 weeks later at the site of vaccination, which can be used clinically as a proof of vaccination. Not all vaccinated ...
Sørup, Signe; Villumsen, Marie; Ravn, Henrik
There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark......, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections....
Tauberg, J A; Nique, T A; Giovannitti, J A
A case is reported in which chronic urticaria developed following local anesthetic administration in a 21-year old Chinese-American male who had presented for routine dental care. An in-depth medical history and intradermal skin-testing failed to disclose a reason for this reaction. Referral to an allergist revealed a previously unknown underlying emotional tension which contributed to the development of chronic urticaria. A brief trial of hydroxyzine (Vistaril), an antihistaminic and anxiolytic medication, was successful in controlling this condition. This case illustrates the importance of the evaluation of the emotional status as a vital component of a comprehensive medical history.
Salmon, J H; Geoffroy, M; Eschard, J P; Ohl, X
Revaxis(®) is a vaccine against diphtheria, tetanus and poliomyelitis (dT-IPV). This vaccine should not be administered by the intradermal or intravenous route. Poor injection techniques and related consequences are rare. We report a case of bursitis associated with reactive glenohumeral effusion complicated by bone erosion occurring after injection of the dT-IPV vaccine. A 26 year old patient was admitted for painful left shoulder causing functional impairment. Control magnetic resonance imaging showed bone oedema on the upper outer part of the humeral head, with a slight cortical irregularity, indicating that the vaccine was injected in contact with the bone at this location, causing erosion. Outcome was favourable after intra-articular corticosteroids. Reports of articular or periarticular injury after vaccination are extremely rare, in view of the substantial number of vaccines administered every year. The potential complications of vaccination are well known to general practitioners but under-reported in the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.
Wei, Lai; Scott, John
Spontaneous adverse event reporting systems are critical tools for monitoring the safety of licensed medical products. Commonly used signal detection algorithms identify disproportionate product-adverse event pairs and may not be sensitive to more complex potential signals. We sought to develop a computationally tractable multivariate data-mining approach to identify product-multiple adverse event associations. We describe an application of stepwise association rule mining (Step-ARM) to detect potential vaccine-symptom group associations in the US Vaccine Adverse Event Reporting System. Step-ARM identifies strong associations between one vaccine and one or more adverse events. To reduce the number of redundant association rules found by Step-ARM, we also propose a clustering method for the post-processing of association rules. In sample applications to a trivalent intradermal inactivated influenza virus vaccine and to measles, mumps, rubella, and varicella (MMRV) vaccine and in simulation studies, we find that Step-ARM can detect a variety of medically coherent potential vaccine-symptom group signals efficiently. In the MMRV example, Step-ARM appears to outperform univariate methods in detecting a known safety signal. Our approach is sensitive to potentially complex signals, which may be particularly important when monitoring novel medical countermeasure products such as pandemic influenza vaccines. The post-processing clustering algorithm improves the applicability of the approach as a screening method to identify patterns that may merit further investigation. Copyright © 2015 John Wiley & Sons, Ltd.
Henchal, L S; Midthun, K; Goldenthal, K L
Various aspects of the development of rotavirus vaccine candidates are discussed. As is true with other vaccines, comprehensive testing must be done to detect the possible presence of adventitious agents in the vaccine and seed preparations. Consideration must also be given to other biologic materials that come in contact with the vaccine preparation during production to prevent the introduction of contaminants. The clinical testing of rotavirus vaccines from early safety and immunogenicity studies through final efficacy studies is also discussed. Issues surrounding coadministration of investigational rotavirus vaccines with US-licensed vaccines are ideally addressed before initiation of efficacy trials. Other subjects discussed are identification of correlates of protection, multivalent vaccines, foreign efficacy trials, safety data, and statistical considerations. Sponsors of investigational vaccines are urged to contact the Food and Drug Administration for guidance during the development process, especially before the investigational new drug application and pivotal efficacy trial stages.
Full Text Available Achieving widespread population immunity by voluntary vaccination poses a major challenge for public health administration and practice. The situation is complicated even more by imperfect vaccines. How the vaccine efficacy affects individuals' vaccination behavior has yet to be fully answered. To address this issue, we combine a simple yet effective game theoretic model of vaccination behavior with an epidemiological process. Our analysis shows that, in a population of self-interested individuals, there exists an overshooting of vaccine uptake levels as the effectiveness of vaccination increases. Moreover, when the basic reproductive number, R0, exceeds a certain threshold, all individuals opt for vaccination for an intermediate region of vaccine efficacy. We further show that increasing effectiveness of vaccination always increases the number of effectively vaccinated individuals and therefore attenuates the epidemic strain. The results suggest that 'number is traded for efficiency': although increases in vaccination effectiveness lead to uptake drops due to free-riding effects, the impact of the epidemic can be better mitigated.
Herve Caspard; Robert P Wise; Amy Steffey; Robert S Brody
Objectives To estimate the proportion of live-attenuated influenza vaccine (LAIV) doses administered beyond expiry date in children and adolescents during influenza seasons 2013-2014 and 2014-2015 in the UK...
Kim, Hyun Jung; Seong, Seok Ju; Shin, Jin Woo; Ju, Woong; Hong, Jin Hwa; Bae, Duk-Soo
After human papillomavirus (HPV) vaccine guidelines published by Korean Society of Gynecologic Oncology (KSGO) in 2011, new studies have been published, leading to additional data regarding efficacy, safety, number of vaccination rounds, and ideal age of vaccine administration. We searched and reviewed the literatures focused on the efficacy of 2-dose schedule vaccination, the efficacy of 3-dose schedule vaccination in middle-aged women, the ideal age of 3-dose schedule vaccination, the safety of HPV preventive vaccine, and the ability of cross-protection of each HPV preventive vaccine. The KSGO has revised the previous guideline based on the results of the above studies. PMID:27029751
Min, Kyung-Jin; Kwon, Sang-Hoon; Kim, Sunghoon; Kim, Hyun Jung; Seong, Seok Ju; Song, Yong Jung; Shin, Jin Woo; Lee, Keun-Ho; Lim, Myong Cheol; Chung, Hyun Hoon; Ju, Woong; Hong, Jin Hwa; Lee, Jeong-Won; Kim, Jae-Weon; Bae, Duk-Soo; Lee, Jae-Kwan
After human papillomavirus (HPV) vaccine guidelines published by Korean Society of Gynecologic Oncology (KSGO) in 2011, new studies have been published, leading to additional data regarding efficacy, safety, number of vaccination rounds, and ideal age of vaccine administration. We searched and reviewed the literatures focused on the efficacy of 2-dose schedule vaccination, the efficacy of 3-dose schedule vaccination in middle-aged women, the ideal age of 3-dose schedule vaccination, the safety of HPV preventive vaccine, and the ability of cross-protection of each HPV preventive vaccine. The KSGO has revised the previous guideline based on the results of the above studies.
Zimet Gregory D; Weiss Thomas W; Rosenthal Susan L; Good Margaret B; Vichnin Michelle D
Abstract Background Despite CDC recommendations regarding universal catch-up vaccination against human papillomavirus (HPV), only about ten percent of young adult women in the United States have been vaccinated. The purpose of this study was to better understand reasons for non-vaccination among insured 19-26 year-old women and to evaluate future vaccination intentions. Methods We used an administrative claims database from a large US managed care plan to identify women aged 19-26 for receipt...
Wells, Timothy S
...-wide smallpox vaccination program. It is designed to complement the collaborative monitoring effort for short-term adverse events associated with the administration of vaccines known as the Vaccine Adverse Events Reporting System (VAERS...
Østerhus, Sven Frederick
The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....
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... multi.html . CDC review information for Multi Pediatric Vaccines: Your Child's First Vaccines: What you need to know (VIS): ... of that vaccine. Tell the person giving the vaccines if your child has ever had a severe reaction after any ...
... 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 ...
A broad spectrum of adverse events is reported following human vaccination but such reactions are considered to be relatively rare. A variety of mechanisms has been proposed to account for such adverse events. These most commonly relate to the actual process of vaccination and range from the vagal reaction associated with anxiety about needle injection, to use of an inappropriate site of administration, or infection of the healthcare worker by accidental injection during needle-capping. Other adverse events directly associated with the vaccine include reversion to virulence of attenuated vaccine strains of organisms, or contamination of the vaccine product. Adverse events may involve immune-mediated phenomena triggered by exposure to the microbial or other components of vaccines. These include: classical IgE-mediated type I hypersensitivity reactions, and immune-complex type III hypersensitivity (Arthus) reactions. Such reactions may be localized or systemic in nature. A variety of autoimmune reactions has been suggested to be triggered by vaccination, but in general the evidence for such associations remains largely anecdotal. Finally, many reported adverse events are simply chance instances of infection or disease onset around the time of vaccination and are not causally associated with administration of vaccine.
Devon J. Shedlock
Full Text Available DNA vaccine-induced immunity can be enhanced by the co-delivery of synthetic gene-encoding molecular adjuvants. Many of these adjuvants have included cytokines, chemokines or co-stimulatory molecules that have been demonstrated to enhance vaccine-induced immunity by increasing the magnitude or type of immune responses and/or protective efficacy. In this way, through the use of adjuvants, immune responses can be highly customizable and functionally tailored for optimal efficacy against pathogen specific (i.e., infectious agent or non-pathogen (i.e., cancer antigens. In the novel study presented here, we examined the use of cellular transcription factors as molecular adjuvants. Specifically the co-delivery of (a RelA, a subunit of the NF-κB transcription complex or (b T-bet, a Th1-specific T box transcription factor, along with a prototypical DNA vaccine expressing HIV-1 proteins was evaluated. As well, all of the vaccines and adjuvants were administered to mice using in vivo electroporation (EP, a technology demonstrated to dramatically increase plasmid DNA transfection and subsequent transgene expression with concomitant enhancement of vaccine induced immune responses. As such, this study demonstrated that co-delivery of either adjuvant resulted in enhanced T and B cell responses, specifically characterized by increased T cell numbers, IFN-γ production, as well as enhanced antibody responses. This study demonstrates the use of cellular transcription factors as adjuvants for enhancing DNA vaccine-induced immunity.
Santos-Lima, Eduardo; B'Chir, Siham; Lane, Andrew
The immunogenicity of a primary series of a new, fully liquid DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim), administered at 2, 4, 6 months of age in four clinical studies is reviewed. Immunogenicity data at 1 month after the third vaccination were assessed and pooled from a total of 1270 participants (per-protocol population) in four randomized clinical trials in Argentina, Mexico, and Peru. Hepatitis B vaccine was not administered at birth. All seroprotection (D, T, polio-1, -2, -3, Hep B, PRP-T [Hib]), seroconversion (PT and FHA), and vaccine response (PT and FHA) data were high, and were similar to licensed comparators (pooled SP, SC, and VR rates were 97.1-100%, 96.0-97.0%, and 99.7-99.9%, respectively). These data show the good immunogenicity of this new hexavalent vaccine that can provide the opportunity to increase global compliance to complex pediatric vaccination schedules. Copyright © 2013. Published by Elsevier Ltd.
Moorthy, Vasee S; Imoukhuede, Egeruan B; Keating, Sheila; Pinder, Margaret; Webster, Daniel; Skinner, Michael A; Gilbert, Sarah C; Walraven, Gijs; Hill, Adrian V S
Successful vaccination against intracellular pathogens, including liver-stage Plasmodium falciparum, will require induction of strong antigen-specific T lymphocyte responses. The multiple epitope (ME)-thrombospondin-related adhesion protein (TRAP) construct includes CD8(+) and CD4(+) T cell epitopes from pre-erythrocytic P. falciparum antigens fused in-frame to the entire pre-erythrocytic antigen TRAP. Three carriers for this construct--plasmid DNA and 2 recombinant nonreplicating poxviruses (modified vaccinia virus Ankara [MVA] and fowlpox strain 9 [FP9])--were administered at 3-week intervals in a heterologous prime-boost combination to 29 Gambian men aged 18-45 years. Doses of DNA ME-TRAP, MVA ME-TRAP, and FP9 ME-TRAP were 2 mg and 1.5x10(8) and 1x10(8) plaque-forming units, respectively. DNA ME-TRAP was injected intramuscularly; MVA ME-TRAP and FP9 ME-TRAP were injected intradermally. There were no clinically relevant laboratory abnormalities and no severe or serious adverse events related to vaccination. DNA/MVA and FP9/MVA regimens were the most potent inducers of circulating effector T cells seen to date in sub-Saharan Africa. Twelve months after the final vaccination, a single booster vaccination expanded the effector T cell pool to a similar or higher magnitude than that after the primary vaccinations. These results highlight optimized combination regimens with general relevance to the development of vaccines targeting intracellular pathogens.
Hull, Brynley P; Menzies, Robert; Macartney, Kristine; McIntyre, Peter B
Strict age limits for receipt of rotavirus vaccines and simultaneous use of vaccines requiring two (Rotarix(®)) and three (RotaTeq(®)) doses in Australia may impact on coverage and timeliness of other vaccines in the infant schedule. Using data from the Australian Childhood Immunisation Register (ACIR), coverage and timeliness of rotavirus vaccines and changes in timeliness of other infant vaccines following rotavirus vaccine introduction was examined, with particular emphasis on Indigenous infants in whom coverage is less optimal. Final dose rotavirus coverage reached 83% within 21 months of program commencement but remained 7% lower than other vaccines due in infancy. Coverage was 11-17% lower in Indigenous infants. Adherence to the first dose upper age limits for rotavirus vaccine was high with >97% of children vaccinated by the recommended age, but for subsequent rotavirus doses, receipt beyond the upper age limits was more common, especially in Indigenous children. Following rotavirus vaccine introduction, there were improvements in timeliness of receipt of all doses of DTPa-containing and 7-valent pneumococcal conjugate vaccines. High population coverage can be attained with rotavirus vaccines, even with adherence to strict upper age restrictions for vaccine dose administration. Rotavirus vaccine introduction appears to have impacted upon the timeliness of other concomitantly scheduled vaccines. These factors should be considered when rotavirus programs are introduced. Copyright © 2013 Elsevier Ltd. All rights reserved.
Korkmaz, Emrullah; Friedrich, Emily E; Ramadan, Mohamed H; Erdos, Geza; Mathers, Alicia R; Burak Ozdoganlar, O; Washburn, Newell R; Falo, Louis D
Tumor necrosis factor-alpha (TNF-α) specific antibodies (anti-TNF-α Ab) have been shown to be potent TNF inhibitors and effective therapeutics for a range of inflammatory diseases. Typically, these drugs are administered systemically, but systemic dosing sufficient to achieve locally effective concentrations in peripheral tissues has been associated with systemic immunosuppression and related adverse events. Here, we evaluated the use of tip-loaded dissolvable microneedle arrays (MNAs) for localized intradermal delivery of anti-TNF-α Ab. MNAs with obelisk shape microneedles that incorporate the antibody cargo in the needle tips were created from carboxymethylcellulose (CMC) using a micromilling/spin-casting fabrication method. We found that anti-TNF-α Ab integrated into MNAs using this room temperature fabrication process maintained conformationally dependent TNF-α binding activity. Further, these MNAs efficiently delivered anti-TNF-α antibodies to the dermis of human skin with clinically applicable release profiles. To evaluate MNA delivered anti-TNF-α Ab function, we applied anti-TNF-α Ab containing MNAs to established psoriasiform lesions on the skin of mice. MNA anti-TNF-α Ab treatment reduced key biomarkers of psoriasiform inflammation including epidermal thickness and IL-1β expression. Taken together, these results demonstrate efficient and biologically effective MNA delivery of anti-TNF-α Ab to the intradermal microenvironment of the skin in mice and humans, and support the development of MNA mediated antibody delivery for clinical applications. Tumor necrosis factor-alpha (TNF-α) specific antibodies (anti-TNF-α Ab) have been shown to be potent TNF inhibitors and effective therapeutics for a range of inflammatory diseases. Typically, these drugs are administered systemically, but systemic dosing sufficient to achieve locally effective concentrations in peripheral tissues has been associated with systemic immunosuppression and related adverse
Riedmann, Eva M.
Long-term effectiveness shown for Merck’s chickenpox vaccine Again—no link between vaccines and autism Experimental ovarian cancer vaccine successful in phase 1 Sinovac’s HFMD vaccine meets phase 3 study goal A vaccine for long-suffering cat allergy patients Vaccines are key to breaking infectious disease-malnutrition cycle Cancer vaccine failures due to the adjuvant IFA? Novartis’ typhoid vaccine make good progress
Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia
Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.
... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... Administration (FDA) is announcing an amendment to the notice of meeting of the Vaccines and Related Biological... announced that a meeting of the Vaccines and Related Biological Products Advisory Committee would be held on...
Cook, Ian F
A 76-year-old male presented with subacromial/subdeltoid bursitis following influenza vaccine administration into the left deltoid muscle. This shoulder injury related to vaccine administration (SIRVA) could have been prevented by the use of a safe, evidence based protocol for the intramuscular injection of the deltoid muscle.
Cook, Ian F
A 76-year-old male presented with subacromial/subdeltoid bursitis following influenza vaccine administration into the left deltoid muscle. This shoulder injury related to vaccine administration (SIRVA) could have been prevented by the use of a safe, evidence based protocol for the intramuscular injection of the deltoid muscle.
Salleras, Luis; Salleras, Montserrat; Soldevila, Nuria; Prat, Andreu; Garrido, Patricio; Domínguez, Ángela
In Western countries, two attenuated varicella vaccines derived from the OKA strain are licensed: Varilrix® GlaxoSmithKline (OKA/RIT strain) and Varivax® Merck Sharp and Dohme (OKA/Merck strain). Currently, in Spain, varicella vaccination is only included in the Ministry of Health, Social Services and Equality official vaccination calendar for administration in adolescents who have not had the disease. Given the good results obtained in Navarra and Madrid with universal administration of the vaccine in children, it would be desirable to include the vaccine in the routine immunization schedule, with the administration of two doses at 15-18 months of age in the future. The protective efficacy of the attenuated herpes zoster vaccine was evaluated in the Shingles Prevention Study, which showed that in the short term (0-4 years) the vaccine reduced the incidence of herpes zoster by 53%, post-herpetic neuralgia by 66%, and the disease burden in immunocompetent persons aged ≥60 years by 61%. Another study demonstrated protective efficacy in persons aged 50-59 years. Over time, the protective efficacy decreases, but remains at acceptable levels, especially for post-herpetic neuralgia and the disease burden. Recently, the results of a controlled clinical trial (phase III) conducted in 18 countries to assess the protective efficacy of the inactivated subunit vaccine (glycoprotein E) adjuvanted with the adjuvant AS01B were published. The study inferred that the vaccine significantly reduced the incidence of herpes zoster in the short term (3.2 years) in people aged ≥50 years. Vaccine protection did not decrease with age at vaccination, ranging between 96.8% and 97.9% in all age groups. Copyright © 2015. Published by Elsevier España, S.L.U.
Full Text Available Cutis verticis gyrata is a rare skin condition characterized by swelling of scalp resembling the surface of the brain. Various conditions, like cerebriform intradermal nevus (CIN, may give rise to this clinical entity. Moreover, its association with cellular blue nevus is extremely rare and has not been reported so far. Here, we report a 28-year-old male with a huge cerebriform swelling covering the occipital lobe along with multiple nodules all over the body. Histology of the scalp swelling showed solitary or clusters of nevus cells in the dermis and from the body lesions showed features of cellular blue nevus. The diagnosis of CIN with cellular blue nevus was confirmed
Peltier, Jacques; Ryan, Matthew W
To compare and correlate wheal size using the Multi-Test II applicator with the endpoint obtained by intradermal dilutional testing (IDT) for common mold allergens. To validate the safety and efficacy of modified quantitative testing (MQT) for determining immunotherapy starting doses. Prospective study of 86 subjects with Multi-Test II and IDT for 6 common mold antigens. There was 84% concordance between IDT results and the results expected from the MQT method. When IDT and MQT results differed, the MQT algorithm predicted a safer endpoint for starting immunotherapy in all but 2 cases. The correlation between Multi-Test II and IDT is not strong enough to infer IDT endpoint from Multi-Test II results for molds. MQT is nearly as effective as formal IDT in determining endpoint. MQT appears to be a safe method for determining starting doses for immunotherapy with fungal allergens.
Schwartz, Kevin L; Tu, Karen; Wing, Laura; Campitelli, Michael A; Crowcroft, Natasha S; Deeks, Shelley L; Wilson, Sarah E; Wilson, Kumanan; Gemmill, Ian; Kwong, Jeffrey C
Ontario has a single payer provincial health insurance program. Administrative data may provide a potentially robust source of information for post-marketing vaccine studies. Vaccine-specific immunization billing codes were introduced in 2011. Our objective was to validate Ontario's universal health care administrative datasets to assess infant immunization status. Electronic medical record data from the Electronic Medical Record Administrative data Linked Database (EMRALD) was used as the reference standard to calculate performance characteristics of the Ontario Health Insurance Plan (OHIP) database vaccine-specific and general immunization codes for 4 primary infant immunizations: diphtheria, tetanus, acellular pertussis, inactivated polio, Haemophilus influenzae type B (DTaP-IPV-Hib) combination vaccine, pneumococcal conjugate vaccine, measles, mumps, rubella (MMR) vaccine, and meningococcal conjugate serogroup C vaccine. OHIP billing claims had specificity ranging from 81% to 92%, sensitivity 70% to 83%, positive predictive value (PPV) 97% to 99%, and negative predictive value (NPV) 13% to 46% for identifying the various specific vaccines in administrative data. For cohorts vaccinated in the new code introduction phase, using both the vaccine-specific and general codes had higher sensitivity than the vaccine-specific codes alone. In conclusion, immunization billing claims from administrative data in Ontario had high specificity and PPV, moderate sensitivity, and low NPV. This study identifies some of the applications of utilizing administrative data for post-marketing vaccine studies. However, limitations of these data decrease their utility for measuring vaccine coverage and effectiveness. Therefore, the establishment of a comprehensive and linkable immunization registry should be a provincial priority.
Christiansen, Cath; Ekeli, Hege [Research and Development, Amersham Health, P.O. Box 4220 Nydalen, 0401 Oslo (Norway); Dreborg, Sten [Alingsaasvaegen 11, 443 35 Lerum (Sweden); Pichler, Werner J. [Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, 3010 Bern (Switzerland)
We report a case of widespread, pruritic macular exanthema appearing 5 days after intravenous administration of the X-ray contrast medium, iohexol (Omnipaque) in a patient who had not previously received any X-ray contrast medium. The eruptions resolved in 7 days, leaving no residual lesions. When the patient was challenged intradermally with the same contrast medium 1.5 months after recovery, the same type of eruption developed 1 day after challenge. Histological examination of biopsies from positive skin test sites revealed the presence of a dermal infiltrate of lymphocytes. This case is another example of a late-onset adverse reaction to an X-ray contrast medium, mediated by specific T cells. The usefulness of intradermal skin testing for confirming the allergic nature of the reaction and for studying cross-reactivity pattern is emphasized. (orig.)
Wiedermann, Ursula; Garner-Spitzer, Erika; Wagner, Angelika
There are 2 major factors responsible for vaccine failures, the first is vaccine-related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2-10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology.
... Vaccines: The Basics Adult Vaccination Resources for Healthcare Professionals ... Influenza vaccine each year to protect against seasonal flu Tdap vaccine to protect against whooping cough and ...
... Vaccines: The Basics Adult Vaccination Resources for Healthcare Professionals ... Influenza vaccine each year to protect against seasonal flu Tdap vaccine to protect against whooping cough and ...
... Vaccines: The Basics Adult Vaccination Resources for Healthcare Professionals ... Influenza vaccine each year to protect against seasonal flu Tdap vaccine to protect against whooping cough and ...
Petersen, Brett W; Damon, Inger K; Pertowski, Carol A; Meaney-Delman, Dana; Guarnizo, Julie T; Beigi, Richard H; Edwards, Kathryn M; Fisher, Margaret C; Frey, Sharon E; Lynfield, Ruth; Willoughby, Rodney E
the effectiveness of the public health response. Such persons will be defined by public health authorities and should be screened for relative contraindications to smallpox vaccination. Relative contraindications include atopic dermatitis (eczema), HIV infection (CD4 cell counts of 50-199 cells/mm3), other immunocompromised states, and vaccine or vaccine-component allergies. Persons with relative contraindications should be vaccinated with Imvamune when available and authorized for use by the Food and Drug Administration. These recommendations will be updated as new data on smallpox vaccines become available and further clinical guidance for other medical countermeasures including antivirals is developed.
Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki
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
Full Text Available In 1988, the World Health Organization (WHO resolved to eradicate poliomyelitis globally. Since then, the initiative has reported dramatic progress in decreasing the incidence of poliomyelitis and limiting the geographical extent of transmission. 2013 is recorded as the second consecutive year not reporting wild poliovirus (WPV from India. If the country can retain this position for one more year India will be declared as polio eradicated. What should be the future vaccination strategies? We searched and reviewed the full text of the available published literature on polio eradication via PubMed and examined Internet sources and websites of major international health agencies. The oral polio vaccine (OPV has been the main tool in the polio eradication program. Once WPV transmission is interrupted, the poliomyelitis will be caused only by OPV. India could expect 1 vaccine-associated paralytic polio per 4.2-4.6 million doses of OPV. Considering the threat of vaccine-derived viruses to polio eradication, WHO urged to develop a strategy to safely discontinue OPV after certification. The ultimate aim is to stop OPV safely and effectively, and eventually substitute with inactivated polio vaccine (IPV. The argument against the use of IPV is its cost. From India, field based data were available on the efficacy of IPV, which was better than OPV. IPV given intradermally resulted in seroconversion rates similar to full-dose intramuscular vaccine. The incremental cost of adopting IPV to replace OPV is relatively low, about US $1 per child per year, and most countries should be able to afford this additional cost.
Horohov, D W; Dunham, J; Liu, C; Betancourt, A; Stewart, J C; Page, A E; Chambers, T M
Adjuvants are included with many inactivated and some modified live vaccines to enhance immune responses to specific antigens. While early vaccines relied exclusively upon aluminum salts, still the major adjuvant used in human vaccines, other adjuvant products are used in veterinary medicine. In addition to enhancing antigen presentation, adjuvants can also enhance the development of specific immune responses. Thus, alum adjuvants often preferentially stimulate humoral immune responses. By contrast, lipid-based adjuvants are often more effective at stimulating cell-mediated immune responses. Metastim(®) is a lipid-based adjuvant reported to elicit both humoral and cellular immune responses, though the mechanism responsible for this activity remains unclear. In this study, we compared the ability of equine influenza virus vaccines containing either saline or Metastim(®) or an aluminum phosphate adjuvant to stimulate antigen presenting cell function in vivo. Six ponies were intradermally inoculated with inactivated equine influenza (KY97) mixed with either adjuvant or saline. Multiple sites were injected so that biopsies could be collected at different times post injection. The 4mm punch biopsies were formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin (H&E). Total RNA was isolated from 2mm punch biopsies for the determination of gene expression by real-time PCR. H&E staining revealed a variety of cells recruited to the injection sites, including lymphocytes, neutrophils, eosinophils and macrophages. Real-time PCR analysis of the injection site confirmed this cellular infiltration and identified increased expression of activation markers. Both vaccines also stimulated gene expressions of pro-inflammatory cytokines. The vaccine containing Metastim(®) elicited significantly higher gene expression of interferon-γ, IL-12, CD4 and CD83 compared to alum (paluminum salt, there was also evidence of Th2 cytokine induction. Copyright © 2015 Elsevier
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
Conclusions: MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed.
Agnete Brunsvik Fredriksen
Full Text Available Background: Idiotopes (Id are antigenic determinants localized in variable (V regions of Ig. Id-specific T and B cells (antibodies play a role in immunotherapy of Id+ tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id+ single chain Fragment variable (scFv from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen presenting cells (APC. APC-specific targeting units were either scFv from APC-specific mAb (anti-MHCII, anti-CD40 or chemokines (MIP-1α, RANTES. Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i Transfected cells secreted plasmid-encoded Id+ fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii Targeted vaccine molecules increased Id-specific B and T cell responses. (iii Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv Targeted Id DNA vaccines induced tumor resistance against challenges with Id+ tumors. (v Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi Human Id+ scFv from 4 multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii Human MIP-1α vaccine proteins enhanced human T cell responses in vitro (viii A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusions: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.
Schutta, Christopher; Barrera, José; Pisano, Melia; Zsak, Laszlo; Grubman, Marvin J; Mayr, Gregory A; Moraes, Mauro P; Kamicker, Barbara J; Brake, David A; Ettyreddy, Damodar; Brough, Douglas E; Butman, Bryan T; Neilan, John G
The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×10(8) to 2.1×10(11) particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R(2)=0.97) and viremia (R(2)=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R(2)=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge. Published by Elsevier Ltd.
Dalton, K P; Nicieza, I; de Llano, D; Gullón, J; Inza, M; Petralanda, M; Arroita, Z; Parra, F
Despite the success of vaccination against myxoma virus, myxomatosis remains a problem on rabbit farms throughout Spain and Europe. In this study we set out to evaluate possible causes of myxoma virus (MYXV) vaccine failures addressing key issues with regard to pathogen, vaccine and vaccination strategies. This was done by genetically characterising MYXV field isolates from farm outbreaks, selecting a representative strain for which to assay its virulence and measuring the protective capability of a commercial vaccine against this strain. Finally, we compare methods (route) of vaccine administration under farm conditions and evaluate immune response in vaccinated rabbits. The data presented here show that the vaccine tested is capable of eliciting protection in rabbits that show high levels of seroconversion. However, the number of animals failing to seroconvert following subcutaneous vaccination may leave a large number of rabbits unprotected following vaccine administration. Successful vaccination requires the strict implication of workable, planned, on farm programs. Following this, analysis to confirm seroconversion rates may be advisable. Factors such as the wild rabbit reservoir, control of biting insects and good hygienic practices must be taken into consideration to prevent vaccine failures from occurring. Copyright © 2015 Elsevier B.V. All rights reserved.
Elizabeth A Specht
Full Text Available Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for molecular pharming in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae are poised to become the next candidate in recombinant subunit vaccine production, and they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally-delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and system immune reactivity.
Specht, Elizabeth A.; Mayfield, Stephen P.
Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for “molecular pharming” in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae could be poised to become the next candidate in recombinant subunit vaccine production, as they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and systemic immune reactivity. PMID:24596570
This thesis analyses the role of an insolvency administrator in insolvency proceedings. It focuses not only on general duties of insolvency administrators in insolvency proceedings, but it also deals with prerequisites necessary to meet in order to be eligible for the function of an insolvency administrator. The thesis presents various types of insolvency administrators, the appointment procedure and changes to the appointment of an insolvency administrator, the possibility to recall, expel a...
... cholera, hepatitis-B, and many more are in the process of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1 Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. African Journal of Biotechnology Vol. 2 (12), pp. 679-683, December 2003 ...