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Sample records for anthrax vaccines

  1. Detailed Safety Review of Anthrax Vaccine Adsorbed

    National Research Council Canada - National Science Library

    2001-01-01

    To date, 18 human studies have assessed the safety of anthrax vaccination. These studies, some stretching back almost 50 years, reported adverse events after vaccination in varying degrees of detail...

  2. Vaccines and bioterrorism: smallpox and anthrax.

    Science.gov (United States)

    Kimmel, Sanford R; Mahoney, Martin C; Zimmerman, Richard K

    2003-01-01

    Because of the success of vaccination and the ring strategy in eradicating smallpox from the world, smallpox vaccine has not been recommended for the United States civilian populations for decades. Given the low but possible threat of bioterrorism, smallpox vaccination is now recommended for those teams investigating potential smallpox cases and for selected personnel of acute-care hospitals who would be needed to care for victims in the event of a terrorist attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In addition to military use, anthrax vaccine is recommended for pre-exposure use in those persons whose work involves repeated exposure to Bacillus anthracis spores.

  3. Military Hospitalizations among Deployed US Service Members Following Anthrax Vaccination, 1998-2001

    National Research Council Canada - National Science Library

    Wells, Timothy S; Sato, Paul A; Smith, Tyler C; Wang, Linda Z; Reed, Robert J; Kappel Ryan, Margaret A

    2006-01-01

    .... To determine if anthrax vaccination was associated with an increased risk of hospitalization, a historical cohort study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken...

  4. Non-Replicating Adenovirus-Vectored Anthrax Vaccine

    International Nuclear Information System (INIS)

    Van Kampen, K. R.; Zhang, J.; Jex, E.; Tang, D. C.

    2007-01-01

    As bioterrorism is emerging as a national threat, it is urgent to develop a new generation of anthrax vaccines that can be rapidly produced and mass administered in an emergency setting. We have demonstrated that protective immunity against anthrax spores could be elicited in mice by intranasal administration of a non-replicating human adenovirus serotype 5 (Ad5)-derived vector encoding Bacillus anthracis protective antigen (PA) in a single-dose regimen. The potency of an Ad5 vector encoding PA was remarkably enhanced by codon optimization of the PA gene to match the tRNA pool found in human cells. This nasal vaccine can be mass-administered by non-medical personnel during a bioterrorist attack. In addition, replication-competent adenovirus (RCA)-free Ad5-vectored anthrax vaccines can be mass produced in PER.C6 cells in serum-free wave bioreactors and purified by column chromatography to meet a surge in demand. The non-replicating nature of this new generation of anthrax vaccine ensures an excellent safety profile for vaccines and the environment.(author)

  5. Anthrax

    Science.gov (United States)

    2017-06-30

    capsule and toxins. Hemorrhagic edema and necrosis of mediastinal lymph nodes ensue. Alveoli show a hemorrhagic exudate and only rarely bacilli...follow cutaneous anthrax and, almost invariably, accompanies inhalational and gastrointestinal anthrax. Vascular injury may result from the proliferation

  6. Anthrax

    Science.gov (United States)

    ... it's most commonly seen in grazing animals like sheep, pigs, cattle, horses, and goats, anthrax also can ... at first, but it rapidly turns into severe pneumonia and requires hospitalization. It usually takes fewer than ...

  7. Anthrax

    Science.gov (United States)

    ... site may get infected. Exams and Tests The health care provider will perform a physical examination. The tests to diagnose anthrax depend on the type of disease that is suspected. A culture of the skin, and sometimes a biopsy , are ...

  8. A 2011 Risk/Benefit Analysis of the Anthrax Vaccine Immunization Program

    Science.gov (United States)

    2011-06-10

    filled with botulinum toxin, 10 with anthrax, and 2 with aflatoxin.‖18 In 1992, Ken Alibek, a senior Russian bioweapons program manager defected...William K. Honner, Rosha A. Loach , Cynthia A. Moore, and J. David Erickson. ―Birth Defects Among Infants Born to Women Who Received Anthrax Vaccine In

  9. Enhancement of an Analytical Method for the Determination of Squalene in Anthrax Vaccine Absorbed Formulations

    National Research Council Canada - National Science Library

    Spanggord, Ronald J; Sun, Meg; Lim, Peter; Ellis, William Y

    2006-01-01

    Specific lots of anthrax vaccine adsorbed administered to members of the U.S. Armed Forces have been alleged to contain squalene, a chemical purported to be associated with illnesses of Gulf War veterans...

  10. The Importance of Health Risk Communication in the Creation of the Anthrax Vaccine Immunization Program

    National Research Council Canada - National Science Library

    Freeman, Bradley

    2001-01-01

    ... press. This paper suggests that a more proactive educational program with a greater utilization of health risk communication techniques would have reduced much of the negative reaction to the anthrax vaccine...

  11. [Properties of live antibiotics-resistant anthrax vaccine STI-PR after long-term storage].

    Science.gov (United States)

    Aksenova, L Iu; Buravtseva, N P; Kogotkova, O I; Eremenko, E I; Tsygankova, O I

    2007-01-01

    Study showed that cultural, morphologic, genetic, immunologic characteristics, and resistance to antibiotics of STI-PR anthrax vaccine did not change after storage during 20 years in lyophilized condition. It has been shown that medium for lyophilization plays important role in preservation of vitality of anthrax spores. Optimal preservative properties have been observed for thioureal and sucrose-gelatinous media for lyophilization. Obtained results give reasons for prolongation of shelf live of STI-PR vaccine from 2 - 3 to 5 - 8 years.

  12. Analysis of anthrax and plague biowarfare vaccine interactions with human monocyte-derived dendritic cells

    NARCIS (Netherlands)

    Skowera, Anna; de Jong, Esther C.; Schuitemaker, Joost H. N.; Allen, Jennifer S.; Wessely, Simon C.; Griffiths, Gareth; Kapsenberg, Martien; Peakman, Mark

    2005-01-01

    The anti-biowarfare anthrax and plague vaccines require repeated dosing to achieve adequate protection. To test the hypothesis that this limited immunogenicity results from the nature of vaccine interactions with the host innate immune system, we investigated molecular and cellular interactions

  13. Recombinant protective antigen 102 (rPA102): profile of a second-generation anthrax vaccine.

    Science.gov (United States)

    Keitel, Wendy A

    2006-08-01

    Recent terrorist attacks involving the use of Bacillus anthracis spores have stimulated interest in the development of new vaccines for anthrax prevention. Studies of the pathogenesis of anthrax and of the immune responses following infection and immunization underscore the pivotal role that antibodies to the protective antigen play in protection. The most promising vaccine candidates contain purified recombinant protective antigen. Clinical trials of one of these, recombinant protective antigen (rPA)102, are underway. Initial results suggest that rPA102 is well tolerated and immunogenic. Additional trials are necessary to identify optimal formulations and immunization regimens for pre- and postexposure prophylaxis. Future licensure of these and other candidate vaccines will depend on their safety and immunogenicity profiles in humans, and their ability to confer protection in animal models of inhalational anthrax.

  14. An Alternative Approach to Combination Vaccines: Intradermal Administration of Isolated Components for Control of Anthrax, Botulism, Plague and Staphylococcal Toxic Shock

    National Research Council Canada - National Science Library

    Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G

    2008-01-01

    ... incompatible vaccine mixtures. Intradermally administered arrays of vaccines for protection from anthrax, botulism, plague, and staphylococcal toxic shock were biocompatible in vivo, retained potent antibody responses...

  15. The anthrax vaccine and research: reactions from postal workers and public health professionals.

    Science.gov (United States)

    Quinn, Sandra Crouse; Thomas, Tammy; Kumar, Supriya

    2008-12-01

    During the 2001 anthrax attacks, public health agencies faced operational and communication decisions about the use of antibiotic prophylaxis and the anthrax vaccine with affected groups, including postal workers. This communication occurred within an evolving situation with incomplete and uncertain data. Guidelines for prophylactic antibiotics changed several times, contributing to confusion and mistrust. At the end of 60 days of taking antibiotics, people were offered an additional 40 days' supply of antibiotics, with or without the anthrax vaccine, the former constituting an investigational new drug protocol. Using data from interviews and focus groups with 65 postal workers in 3 sites and structured interviews with 16 public health professionals, this article examines the challenges for public health professionals who were responsible for communication with postal workers about the vaccine. Multiple factors affected the response, including a lack of trust, risk perception, disagreement about the recommendation, and the controversy over the military's use of the vaccine. Some postal workers reacted with suspicion to the vaccine offer, believing that they were the subjects of research, and some African American workers specifically drew an analogy to the Tuskegee syphilis study. The consent forms required for the protocol heightened mistrust. Postal workers also had complex and ambivalent responses to additional research on their health. The anthrax attacks present us with an opportunity to understand the challenges of communication in the context of uncertain science and suggest key strategies that may improve communications about vaccines and other drugs authorized for experimental use in future public health emergencies.

  16. The anthrax vaccine: is it safe? does it work?

    National Research Council Canada - National Science Library

    Committee to Assess the Safety and Efficacy of the Anthrax Vaccine, Medical Follow-Up Agency

    2002-01-01

    ...), was licensed in 1970. It was initially used to protect people who might be exposed to anthrax where they worked, such as veterinarians and textile plant workers who process animal hair. When the U...

  17. Progress and novel strategies in vaccine development and treatment of anthrax.

    Science.gov (United States)

    Chitlaru, Theodor; Altboum, Zeev; Reuveny, Shaul; Shafferman, Avigdor

    2011-01-01

    The lethal anthrax disease is caused by spores of the gram-positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio-terror weapon. Protective antigen (PA), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti-PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti-toxemic and anti-bacteremic prophylactic treatment of anthrax requires prolonged antibiotic administration. Shorter efficient postexposure treatments may require active or passive immunization, in addition to antibiotics. Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long-lasting protection conferred by PA immunization. The search for such novel factors is the focus of several high throughput genomic and proteomic studies that are already leading to identification of novel targets for therapeutics, for vaccine candidates, as well as biomarkers for detection and diagnosis. © 2010 John Wiley & Sons A/S.

  18. Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control.

    Science.gov (United States)

    Kracalik, Ian T; Kenu, Ernest; Ayamdooh, Evans Nsoh; Allegye-Cudjoe, Emmanuel; Polkuu, Paul Nokuma; Frimpong, Joseph Asamoah; Nyarko, Kofi Mensah; Bower, William A; Traxler, Rita; Blackburn, Jason K

    2017-10-01

    Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock vaccines in controlling anthrax, underreporting, logistics, and limited resources makes implementing vaccination campaigns difficult. To better understand the geographic limits of anthrax, elucidate environmental factors related to its occurrence, and identify human and livestock populations at risk, we developed predictive models of the environmental suitability of anthrax in Ghana. We obtained data on the location and date of livestock anthrax from veterinary and outbreak response records in Ghana during 2005-2016, as well as livestock vaccination registers and population estimates of characteristically high-risk groups. To predict the environmental suitability of anthrax, we used an ensemble of random forest (RF) models built using a combination of climatic and environmental factors. From 2005 through the first six months of 2016, there were 67 anthrax outbreaks (851 cases) in livestock; outbreaks showed a seasonal peak during February through April and primarily involved cattle. There was a median of 19,709 vaccine doses [range: 0-175 thousand] administered annually. Results from the RF model suggest a marked ecological divide separating the broad areas of environmental suitability in northern Ghana from the southern part of the country. Increasing alkaline soil pH was associated with a higher probability of anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5) million livestock and 805 (95% CI: 519, 890) thousand low income rural livestock keepers were located in anthrax risk areas. Based on our estimates, the current anthrax vaccination efforts in Ghana cover a fraction of the livestock potentially at risk, thus control efforts should be focused on improving vaccine coverage among high risk groups.

  19. Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control.

    Directory of Open Access Journals (Sweden)

    Ian T Kracalik

    2017-10-01

    Full Text Available Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock vaccines in controlling anthrax, underreporting, logistics, and limited resources makes implementing vaccination campaigns difficult. To better understand the geographic limits of anthrax, elucidate environmental factors related to its occurrence, and identify human and livestock populations at risk, we developed predictive models of the environmental suitability of anthrax in Ghana. We obtained data on the location and date of livestock anthrax from veterinary and outbreak response records in Ghana during 2005-2016, as well as livestock vaccination registers and population estimates of characteristically high-risk groups. To predict the environmental suitability of anthrax, we used an ensemble of random forest (RF models built using a combination of climatic and environmental factors. From 2005 through the first six months of 2016, there were 67 anthrax outbreaks (851 cases in livestock; outbreaks showed a seasonal peak during February through April and primarily involved cattle. There was a median of 19,709 vaccine doses [range: 0-175 thousand] administered annually. Results from the RF model suggest a marked ecological divide separating the broad areas of environmental suitability in northern Ghana from the southern part of the country. Increasing alkaline soil pH was associated with a higher probability of anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5 million livestock and 805 (95% CI: 519, 890 thousand low income rural livestock keepers were located in anthrax risk areas. Based on our estimates, the current anthrax vaccination efforts in Ghana cover a fraction of the livestock potentially at risk, thus control efforts should be focused on improving vaccine coverage among high risk groups.

  20. [PERSPECTIVES OF DEVELOPMENT OF LIVE RECOMBINANT ANTHRAX VACCINES BASED ON OPPORTUNISTIC AND APATHOGENIC MICROORGANISMS].

    Science.gov (United States)

    Popova, P Yu; Mikshis, N I

    2016-01-01

    Live genetic engineering anthrax vaccines on the platform of avirulent and probiotic micro-organisms are a safe and adequate alternative to preparations based on attenuated Bacillus anthracis strains. Mucosal application results in a direct contact of the vaccine preparations with mucous membranes in those organs arid tissues of the macro-organisms, that are exposed to the pathogen in the first place, resulting in a development of local and systemic immune response. Live recombinant anthrax vaccines could be used both separately as well as in a prime-boost immunization scheme. The review focuses on immunogenic and protective properties of experimental live genetic engineering prearations, created based on members of geni of Salmonella, Lactobacillus and adenoviruses.

  1. The Anthrax Vaccine Debate: A Medical Review for Commanders

    National Research Council Canada - National Science Library

    Hersack, Richard

    2001-01-01

    .... The policy decision to vaccinate is based on an assessment of relative risk. The risk to an individual of developing side effects and complications after vaccination versus, the risk that Defense Department (DoD...

  2. Changing patterns of human anthrax in Azerbaijan during the post-Soviet and preemptive livestock vaccination eras.

    Directory of Open Access Journals (Sweden)

    Ian Kracalik

    2014-07-01

    Full Text Available We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of (+11.95% from 1984 to 1995 followed by declining rate of -35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated "One Health" approach that takes into account the changing geographic distribution of the disease.

  3. A Viral Nanoparticle with Dual Function as an Anthrax Antitoxin and Vaccine

    Science.gov (United States)

    Manayani, Darly J; Thomas, Diane; Dryden, Kelly A; Reddy, Vijay; Siladi, Marc E; Marlett, John M; Rainey, G. Jonah A; Pique, Michael E; Scobie, Heather M; Yeager, Mark; Young, John A. T; Manchester, Marianne; Schneemann, Anette

    2007-01-01

    The recent use of Bacillus anthracis as a bioweapon has stimulated the search for novel antitoxins and vaccines that act rapidly and with minimal adverse effects. B. anthracis produces an AB-type toxin composed of the receptor-binding moiety protective antigen (PA) and the enzymatic moieties edema factor and lethal factor. PA is a key target for both antitoxin and vaccine development. We used the icosahedral insect virus Flock House virus as a platform to display 180 copies of the high affinity, PA-binding von Willebrand A domain of the ANTXR2 cellular receptor. The chimeric virus-like particles (VLPs) correctly displayed the receptor von Willebrand A domain on their surface and inhibited lethal toxin action in in vitro and in vivo models of anthrax intoxication. Moreover, VLPs complexed with PA elicited a potent toxin-neutralizing antibody response that protected rats from anthrax lethal toxin challenge after a single immunization without adjuvant. This recombinant VLP platform represents a novel and highly effective, dually-acting reagent for treatment and protection against anthrax. PMID:17922572

  4. Vaccine-induced protection against anthrax in cheetah (Acinonyx jubatus) and black rhinoceros (Diceros bicornis).

    Science.gov (United States)

    Turnbull, P C B; Tindall, B W; Coetzee, J D; Conradie, C M; Bull, R L; Lindeque, P M; Huebschle, O J B

    2004-09-03

    Institution of a policy of vaccination in endangered species with a vaccine not previously administered to it cannot be undertaken lightly. This applies even more in the case of cheetah (Acinonyx jubatus) with their unusually monomorphic gene pool and the potential restrictions this places on their immune responses. However, the recently observed mortalities from anthrax in these animals in the Etosha National Park, Namibia, made it imperative to evaluate vaccination. Black rhinoceros (Diceros bicornis), another endangered species in the park, have been vaccinated for over three decades but the effectiveness of this has never been evaluated. Passive protection tests in A/J mice using sera from 12 cheetahs together with enzyme immunoassay indicated that cheetah are able to mount seemingly normal primary and secondary humoral immune responses to the Sterne 34F2 live spore livestock vaccine. Overall protection rates in mice injected with the sera rose and fell in concert with rises and declines in antibody titres, although fine analysis showed that the correlation between titre and protection was complex. Once a high level of protection (96% of mice 1 month after a second booster in the cheetahs) had been achieved, the duration of substantial protection appeared good (60% of the mice 5 months after the second booster). Protection conferred on mice by sera from three of four vaccinated rhino was almost complete, but, obscurely, none of the mice receiving serum from the fourth rhino were protected. Sera from three park lions with naturally acquired high antibody titres, included as controls, also conferred high levels of protection. For the purposes of wildlife management, the conclusions were that vaccination of cheetah with the standard animal anthrax vaccine causes no observable ill effect in the animals and does appear to confer protective immunity. At least one well-separated booster does appear to be desirable. Vaccination of rhino also appears to be justified

  5. 9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

    Science.gov (United States)

    2010-01-01

    ...) Forty-two susceptible guinea pigs from the same source each weighing 400 to 500 grams, shall be used as... conducted. The guinea pigs used as vaccinates shall be injected as recommended on the label with a... and controls shall each be challenged with not less than 4,500 guinea pig LD50 of a virulent...

  6. Glassy-state stabilization of a dominant negative inhibitor anthrax vaccine containing aluminum hydroxide and glycopyranoside lipid A adjuvants.

    Science.gov (United States)

    Hassett, Kimberly J; Vance, David J; Jain, Nishant K; Sahni, Neha; Rabia, Lilia A; Cousins, Megan C; Joshi, Sangeeta; Volkin, David B; Middaugh, C Russell; Mantis, Nicholas J; Carpenter, John F; Randolph, Theodore W

    2015-02-01

    During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, dominant negative inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40°C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40°C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40°C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40°C were observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Anthrax: Diagnosis

    Science.gov (United States)

    ... Diagnosis Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir Doctors in the United States rarely see a patient with anthrax. CDC Guidance and case definitions are available to help doctors diagnose anthrax, take ...

  8. Simultaneous immunization of cattle with foot-and-mouth disease (FMD and live anthrax vaccines do not interfere with FMD booster responses

    Directory of Open Access Journals (Sweden)

    Myrian Trotta

    2015-01-01

    Full Text Available Foot-and-mouth disease (FMD vaccination in Argentina is compulsory for most of the cattle population and conducted by certified veterinarians. This organized campaign may facilitate the controlled application of other vaccines against endemic diseases, provided immune responses against FMD are not hindered. There is no published information on the interference of immunity against FMD vaccines when applied together with a live bacterial vaccine. In this study we evaluated if the simultaneous application of a Bacillus anthracis live vaccine with a commercial tetravalent oil-based FMD vaccine (FMD-vac used in Argentina, modifies the antibody booster responses against FMD virus (FMDV in cattle. Two groups of 16 heifers with comparable liquid phase blocking ELISA (LPBE titers were immunized with the FMD-vac alone or simultaneously with a commercial attenuated bovine anthrax Sterne strain vaccine (ABV. Serum samples were obtained at 0, 25, 60 and 90 days post vaccination (dpv and specific antibodies against two FMDV vaccine strains were assessed by LPBE, avidity and IgG-isotype ELISAs. Bovines immunized with FMD-vac or FMDV-V + ABV responded with a boost in the LPBE antibody titers and avidity at 25 dpv, and remained within similar levels up to the end of the study. Animals vaccinated with FMD-vac + ABV had significantly higher LPBE titers at 25 dpv, compared to those immunized with FMD-vac alone; which was due to an increase in IgG2 titers. Overall, antibody titers elicited in both groups were similar and followed comparable kinetics over time. We conclude that the simultaneous application of a live anthrax vaccine with the current FMD tetravalent vaccine used in Argentina in cattle previously immunized against FMD, did not counteract the serological response induced by FMD vaccination.

  9. Uso de la vacuna contra el carbunco en los Estados Unidos de América Use of anthrax vaccine in the United States of America: recommendations of the Advisory Committee on Immunization Practices

    Directory of Open Access Journals (Sweden)

    2001-07-01

    Full Text Available This piece presents the recommendations of the Advisory Committee on Immunization Practices of the United States of America concerning the use of aluminum hydroxide adsorbed cell-free anthrax vaccine (Anthrax Vaccine Adsorbed, or AVA and the use of chemoprophylaxis against Bacillus anthracis in the United States. The recommended vaccination schedule consists of three subcutaneous injections, at 0, 2, and 4 weeks, and three booster vaccinations, at 6, 12, and 18 months. To maintain immunity, an annual booster injection is recommended. Approximately 95% of vaccinees seroconvert, with a fourfold rise in anti-PA (protective antigen IgG titers after three doses. Analysis of data from the United States' Vaccine Adverse Event Reporting System has documented no pattern of serious adverse events clearly associated with the vaccine, except injection-site reactions. Vaccination is contraindicated in the case of a previous history of anthrax infection or anaphylactic reaction following a previous dose of AVA or any of the vaccine components. In addition, vaccination should be postponed in the case of moderate or severe acute illness. Pregnant women should be vaccinated against anthrax only if the potential benefits of vaccination outweigh the potential risks to the fetus. Vaccination during breast-feeding is not medically contraindicated. Routine preexposure vaccination with AVA is indicated for persons engaged in: a work involving production quantities or concentrations of B. anthracis cultures or b activities with a high potential for aerosol production. For the military and other select populations or for groups for which a calculable risk can be assessed, preexposure vaccination may be indicated. Following confirmed or suspected exposure to B. anthracis, postexposure antibiotic prophylaxis should be administered with ciprofloxacin, ofloxacin, doxycycline, penicillin VK, or amoxicillin. If the vaccine is available, prophylaxis should continue for 4 weeks

  10. Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA) vaccine to prevent anthrax in adults.

    Science.gov (United States)

    Brown, Bruce K; Cox, Josephine; Gillis, Anita; VanCott, Thomas C; Marovich, Mary; Milazzo, Mark; Antonille, Tanya Santelli; Wieczorek, Lindsay; McKee, Kelly T; Metcalfe, Karen; Mallory, Raburn M; Birx, Deborah; Polonis, Victoria R; Robb, Merlin L

    2010-11-05

    The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA). A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. ClinicalTrials.gov NCT00057525.

  11. Anthrax Remembered

    Centers for Disease Control (CDC) Podcasts

    2015-08-03

    Dr. John Jernigan and Dr. D. Peter Drotman recall the 2001 anthrax attacks and rapid publication of the landmark paper reporting the initial cases of inhalational anthrax.  Created: 8/3/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/3/2015.

  12. Anthrax blood test

    Science.gov (United States)

    Anthrax serology test; Antibody test for anthrax; Serologic test for B. anthracis ... This test may be performed when the health care provider suspects you have anthrax infection. The bacteria that cause ...

  13. Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

    Science.gov (United States)

    Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

    2006-11-17

    The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

  14. Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.

    Science.gov (United States)

    Wright, Jennifer G; Plikaytis, Brian D; Rose, Charles E; Parker, Scott D; Babcock, Janiine; Keitel, Wendy; El Sahly, Hana; Poland, Gregory A; Jacobson, Robert M; Keyserling, Harry L; Semenova, Vera A; Li, Han; Schiffer, Jarad; Dababneh, Hanan; Martin, Sandra K; Martin, Stacey W; Marano, Nina; Messonnier, Nancy E; Quinn, Conrad P

    2014-02-12

    We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at

  15. Factors associated with repeated outbreak of anthrax in Bangladesh: qualitative and quantitative study

    Directory of Open Access Journals (Sweden)

    Jayedul Hassan

    2015-06-01

    Full Text Available Anthrax, caused by Bacillus anthracis is an acute, febrile disease of warm blooded animals including humans. Social norms and poverty in addition to climatic factors such as soil conditions, seasons of year, ambient temperature and rainfall influence the persistence of the B. anthracis and anthrax outbreaks. The present study was designed to reveal the factors influencing the repeated outbreak of anthrax in Bangladesh. Considering the previous outbreaks of anthrax, Sirajganj, Bogra, Kushtia, Tangail and Mymensingh districts of Bangladesh were selected for this study. To elucidate the factors, qualitative data relating to the animal management, knowledge and behavior of the people; and quantitative data relating to soil conditions, ambient temperature and rainfall were acquired, and analyzed critically. Based on the outbreak histories, a year was divided into two seasons, anthrax prone season (May-November and anthrax dry season (December-April. Anthrax spores could be isolated from 11.67% (n=14/120 of the soil samples collected from the study areas. The present study revealed that poor knowledge, lack of awareness, improper carcass disposal, inadequate vaccination, high Ca content and moisture in the soil along with high ambient temperature and rainfall during the anthrax prone season were the possible influencing factors of repeated outbreaks of anthrax in the study areas. Intensive propaganda to create public awareness of anthrax together with proper vaccination may reduce anthrax outbreaks in Bangladesh.

  16. Inhalation Anthrax (Ames aerosol) in Naive and Vaccinated New Zealand Rabbits: Characterizing the Spread of Bacteria from Lung Deposition to Bacteremia

    Science.gov (United States)

    2012-06-28

    Lond.) 51, 372–385. Henderson, D. W., Peacock , S., and Belton, F. C. (1956). Observations on the prophylaxis of experimental pulmonary anthrax in...terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums

  17. Modeling the Ecological Niche of Bacillus anthracis to Map Anthrax Risk in Kyrgyzstan.

    Science.gov (United States)

    Blackburn, Jason K; Matakarimov, Saitbek; Kozhokeeva, Sabira; Tagaeva, Zhyldyz; Bell, Lindsay K; Kracalik, Ian T; Zhunushov, Asankadyr

    2017-03-01

    AbstractAnthrax, caused by the environmental bacterium Bacillus anthracis , is an important zoonosis nearly worldwide. In Central Asia, anthrax represents a major veterinary and public health concern. In the Republic of Kyrgyzstan, ongoing anthrax outbreaks have been reported in humans associated with handling infected livestock and contaminated animal by-products such as meat or hides. The current anthrax situation has prompted calls for improved insights into the epidemiology, ecology, and spatial distribution of the disease in Kyrgyzstan to better inform control and surveillance. Disease control for both humans and livestock relies on annual livestock vaccination ahead of outbreaks. Toward this, we used a historic database of livestock anthrax reported from 1932 to 2006 mapped at high resolution to develop an ecological niche model-based prediction of B. anthracis across Kyrgyzstan and identified spatial clusters of livestock anthrax using a cluster morphology statistic. We also defined the seasonality of outbreaks in livestock. Cattle were the most frequently reported across the time period, with the greatest number of cases in late summer months. Our niche models defined four areas as suitable to support pathogen persistence, the plateaus near Talas and Bishkek, the valleys of western Kyrgyzstan along the Fergana Valley, and the low-lying areas along the shore of Lake Isyk-Kul. These areas should be considered "at risk" for livestock anthrax and subsequent human cases. Areas defined by the niche models can be used to prioritize anthrax surveillance and inform efforts to target livestock vaccination campaigns.

  18. The pattern of anthrax cases on livestock in West Nusa Tenggara Province

    Directory of Open Access Journals (Sweden)

    Enymartindah

    1998-03-01

    Full Text Available A retrospective study on anthrax in endemic area was carried out from 1984 to 1994 in West Nusa Tenggara Province (NTB to uncover the occurrence of anthrax and the pattern of the disease in livestock. Data of anthrax incidence had been compiled for the 11 years from Animal Health Section and Type B Laboratory of the Livestock Service Office, NTB Province in Mataram. This was done to get the information about locations and times when the cases occurred, and the vaccination status of livestock in the anthrax area. The pattern of anthrax in livestock was analyzed by using time series analysis, and the long term trend was then illustrated by linier regression . During the years, anthrax cases in livestock were reported high in Sumbawa island, while the cases in Lombok island were relatively low. There were no anthrax cases reported from East Lombok District . The long term trend of anthrax occurrence in livestock from 1984 to 1994 tended to decrease (Y= 6,04 - 0,0162 X.

  19. Anthrax of the eyelids.

    Science.gov (United States)

    Amraoui, A.; Tabbara, K. F.; Zaghloul, K.

    1992-01-01

    Anthrax is a disease caused by Bacillus anthracis. The disease affects primarily herbivores including sheep, cattle, horses, and other domestic animals. Humans may rarely be affected. We examined one male and two female patients with a localised itchy erythematous papule of the eyelid. A necrotising ulcer formed in each of the three cases resulting in a black lesion. Scraping in each case showed Gram positive rods and culture grew Bacillus anthracis. All three patients responded to the intravenous administration of penicillin G, and the lesion resolved leaving scars in two cases. Anthrax is a rare disease but should be considered in the differential diagnosis of ulcers or pustules of the eyelids. Images PMID:1486081

  20. 2014 Anthrax epidemic in Koubia prefecture, Guinea-Conakry.

    Science.gov (United States)

    Sow, M S; Boushab, M B; Balde, H; Camara, A; Sako, F B; Traoré, F A; Diallo, M O S; Diallo, M D; Keita, M; Sylla, A O; Tounkara, T M; Cissé, M

    2016-11-01

    Anthrax disease is an anthropozoonosis caused by a Gram-positive bacterium, Bacillus anthracis. Our objective was to describe the epidemiological, clinical and therapeutic features of the 2014 epidemic in Koubia prefecture. This retrospective study examined all of the anthrax cases reported in Fafaya, Koubia Prefecture. In March and April 2014, there were 39 cases of human anthrax reported, for an incidence of 1.135%. The mean age was 20.9 (± 18.3) with a sex ratio of 2.54 (28/11) in favor of men. Seventy-six percent (23/39) were single. More than one half were students (53.8%). The main clinical signs were fever in 71, 8% (n = 28 /), papules 59% (n = 23), vesicles of 59% (n = 23) Digestive and cutaneous signs represented 35.9 % and 64.1% respectively; 35% had ingested contaminated meat and 17.95% were in direct contact with a sick animal. We didn't find any correlation between the mode of infection and onset of signs. The fatality rate was 28.21%. The 2014 epidemic of anthrax disease in the Koubia prefecture was marked by a high incidence and lethality. Clinical manifestations were cutaneaous and digestive. These results may serve further interventions to fight against anthrax disease. They should mainly focus on an awareness of peasants, surveillance and vaccination of cattle. Other studies seem to be necessary.

  1. [Anthrax due to deliberate infection

    NARCIS (Netherlands)

    Dissel, J.T. van; Kullberg, B.J.; Berg, P.C. van den; Steenbergen, J.E. van

    2001-01-01

    Anthrax is a zoonosis which is particularly prevalent in cattle, goats and sheep and is caused by Bacillus anthracis, a Gram-positive spore forming aerobic microorganism. The endospores can survive outside of the body for many decades. The natural form of anthrax has a cutaneous, pulmonary and

  2. Anthrax, People and Dead Hippos

    Centers for Disease Control (CDC) Podcasts

    2017-11-07

    Epidemiologist, Dr. Melissa Marx, discuses anthrax deaths in people who ate dead hippos.  Created: 11/7/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/7/2017.

  3. Anthrax does not forgive mistakes: the information assessment following the yamal peninsula outbreak in the summer of 2016

    Directory of Open Access Journals (Sweden)

    I. V. Shestakova

    2017-01-01

    Full Text Available For the first time in a long time period the sources of actual information about anthrax in Russia and in the world are systematized. The essence of the problem, features of epidemiology and clinical manifestations of the current forms of anthrax disease are analyzed. The upgraded classification of anthrax is presented, the clinical manifestations of oro-oropharyngeal varieties of intestinal form and injectable form of anthrax are described, according to extensive literature data and international guidelines and recommendations. The recommendations for clinical management of patients and diagnosis of disease are given. The need for strict compliance to the vaccination requirements of anthrax among animals and persons from risk groups is proven.

  4. Awareness and attitudes towards anthrax and meat consumption practices among affected communities in Zambia: A mixed methods approach.

    Directory of Open Access Journals (Sweden)

    Doreen Chilolo Sitali

    2017-05-01

    Full Text Available In Zambia, human anthrax cases often occur following cases of animal anthrax. Human behaviour has been implicated in this transmission. The objective of the study was to explore human behavioural patterns that may contribute to outbreaks of anthrax among affected communities.A mixed methods study was conducted in four districts of Zambia from November 2015 to February 2016. A cross sectional survey involving 1,127 respondents, six focus group discussions and seven key informant interviews with professional staff were conducted. Descriptive statistics on socio-demographic characteristics, awareness of anthrax, attitudes towards cattle vaccination and risk factors for anthrax and vaccination practices were run using STATA 12 for analysis.Overall, 88% of respondents heard about anthrax, 85.1% were aware that anthrax is transmitted by eating infected meat and 64.2% knew that animals and humans can be infected with anthrax. However, qualitative data suggested that awareness of anthrax varied across communities. Qualitative findings also indicated that, in Western and Muchinga provinces, human anthrax was transmitted by eating infected beef and hippo (Hippopotamus amphibious meat, respectively. Although survey data indicated that 62.2% of respondents vaccinated their animals, qualitative interviews and annual vaccination reports indicated low vaccination rates, which were attributed to inadequate veterinary service provision and logistical challenges. While 82% of respondents indicated that they reported animal deaths to veterinary officers, only 13.5% of respondents buried infected carcasses. Majority (78.1% of respondents either ate, sold or shared meat from dead animals with other community members. Poverty, lack of access to meat protein and economic reasons were cited as drivers for consuming infected meat.Health education campaigns must be intensified to reduce the risk of human exposure. Veterinary extension services should be strengthened and

  5. Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant

    OpenAIRE

    Kelly, Cassandra D; O'Loughlin, Chris; Gelder, Frank B; Peterson, Johnny W; Sower, Laurie E; Cirino, Nick M

    2007-01-01

    Background There is a clear need for vaccines and therapeutics for potential biological weapons of mass destruction and emerging diseases. Anthrax, caused by the bacterium Bacillus anthracis, has been used as both a biological warfare agent and bioterrorist weapon previously. Although antibiotic therapy is effective in the early stages of anthrax infection, it does not have any effect once exposed individuals become symptomatic due to B. anthracis exotoxin accumulation. The bipartite exotoxin...

  6. Radiologic findings of the anthrax: focus on alimentary anthrax

    International Nuclear Information System (INIS)

    Kim, Sung Woo; Kim, Won Ho; Yang, Geun Seok; Kim, Tae Hun; Kang, Duk Sik

    1995-01-01

    To evaluate the radiologic findings of alimentary anthrax. 19 patients with alimentary anthrax, which was caused by ingestion of contaminated beef, were included in this study. The diagnosis was made by demonstration of Bacillus anthracis in smear and culture of the contaminated meat. We evaluated the clinical manifestations and the findings of thoracic, abdominal radiographs, cervical, abdominal ultrasonograms and abdominal CT scans. Out of the 19 patients with the alimentary infection, 9 had oropharyngeal form, 18 had abdominal form and 8 had combination of oropharyngeal and abdominal form. The patients had general symptoms and signs such as fever, chill, myalgia. Clinical symptoms and signs were sore throat, throat injection, throat ulcer and patch in oropharyngeal form, and nausea, vomiting abdominal pain, diarrhea, and gross GI bleeding in abdominal form. Radiologic findings included enlarged cervical lymph nodes (36%) in oropharyngeal form, and paralytic ileus (26%), ascites (26%), hepatomegaly (21%), enlarged mesenteric lymph nodes (26%), small bowel wall thickening (5%) in abdominal form. In two patients, late complications occurred as intestinal obstruction due to ileal stricture with perforation, and inflammatory changes of pelvic cavity due to ileovesical fistula. Radiologic findings of alimentary anthrax are difficult in differentiation from those of other inflammatory bowel disease, but those radiologic findings with clinical manifestations may be helpful in diagnosis and evaluation of disease process in patients with alimentary anthrax

  7. Orbito-Maxillofacial Cutaneous Anthrax

    African Journals Online (AJOL)

    and development of a black eschar were reviewed. Occupational history, falls and/or contact with animal meat was ... and oral ciprofloxacin (500mg BD for 21 days). The culture results isolated Bacillus anthracis highly ... The clinical evolution of cutaneous anthrax is typical with the initial development of minute red macules.

  8. Comparison of the Structural Stability and Dynamic Properties of Recombinant Anthrax Protective Antigen and its 2-Fluorohistidine Labeled Analogue

    OpenAIRE

    Hu, Lei; Joshi, Sangeeta B.; Andra, Kiran K.; Thakkar, Santosh V.; Volkin, David B.; Bann, James G.; Middaugh, C. Russell

    2012-01-01

    Protective antigen (PA) is the primary protein antigenic component of both the currently used anthrax vaccine and related recombinant vaccines under development. An analogue of recombinant PA (2-FHis rPA) has been recently shown to block the key steps of pore formation in the process of inducing cytotoxicity in cells, and thus can potentially be used as an antitoxin or a vaccine. This rPA analogue was produced by fermentation to incorporate the unnatural amino acid 2-fluorohistidine (2-FHis)....

  9. The anthrax letters: a medical detective story

    National Research Council Canada - National Science Library

    Cole, Leonard A

    2003-01-01

    .... Library of Congress Cataloging-in-Publication Data Cole, Leonard A., 1933The anthrax letters : a medical detective story / Leonard A. Cole. p. cm. Includes bibliographical references and index. ISBN 0-309-08881-X - ISBN 0-309-52584-5 (PDF) 1. Bioterrorism- United States. 2. Anthrax- United States. 3. Postal service- United States. 4. Victims of...

  10. Treatment of Anthrax Disease Frequently Asked Questions

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Young, Joan E.; Lesperance, Ann M.; Malone, John D.

    2010-05-14

    This document provides a summary of Frequently Asked Questions (FAQs) on the treatment of anthrax disease caused by a wide-area release of Bacillus anthracis spores as an act bioterrorism. These FAQs are intended to provide the public health and medical community, as well as others, with guidance and communications to support the response and long-term recovery from an anthrax event.

  11. Anthrax Meningitis - Report Of An Autopsied Case

    Directory of Open Access Journals (Sweden)

    Mahadevan A

    1999-01-01

    Full Text Available Anthrax is a rare cause of hemorrhagic meningitis in man. This report illustrates the characteristic hemorrhagic manifestations in the brain of a patient dying of anthrax meningitis secondary to overwhelming bacteremia. Gross examination of the brain revealed a thick dense subarachnoid hemorrhage with numerous petechial hemorrhages in the cortex. Histologically, meningoencephalitis with vascular necrosis, edema, perivascular cortical hemorrhages and clumps of Gram positive bacilli in the vascular lumen and invading vessel wall were the salient features. The anthrax bacillus was isolated from CSF and brain tissue and further its pathogenecity was confirmed by animal inoculation.

  12. Rabies virus glycoprotein as a carrier for anthrax protective antigen

    International Nuclear Information System (INIS)

    Smith, Mary Ellen; Koser, Martin; Xiao Sa; Siler, Catherine; McGettigan, James P.; Calkins, Catherine; Pomerantz, Roger J.; Dietzschold, Bernhard; Schnell, Matthias J.

    2006-01-01

    Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule, we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems

  13. Human and animal anthrax in Ethiopia: A retrospective record ...

    African Journals Online (AJOL)

    26,737 animal anthrax cases (human to animal ratio 1:5) were reported from 2009 to 2013 ... respectively) This data analysis revealed that less number of human anthrax cases ..... quality to reach to strong conclusions and recommendations.

  14. Anthrax in Vintage Animal-hair Shaving Brushes

    Centers for Disease Control (CDC) Podcasts

    2017-08-08

    Dr. Kate Hendricks, a CDC anthrax expert, discusses anthrax in vintage shaving brushes.  Created: 8/8/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/8/2017.

  15. Anthrax

    Science.gov (United States)

    2009-01-01

    chest radiograph will almost always exhibit a widened mediastinal contour that includes unilat- eral or bilateral hilar enlargement , as. well as...express B-Iactamase variants, peni - cillinases and cephalosporinases, which would undermine a lone-penicillin therapy (Lightfoot et ai., 1990

  16. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    Directory of Open Access Journals (Sweden)

    T. Scott Devera

    2015-06-01

    Full Text Available Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI, and hepatic alanine aminotransferase (ALT, and aspartate aminotransferase (AST, it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

  17. [VACCINES].

    Science.gov (United States)

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

  18. The medicinal chemistry of botulinum, ricin and anthrax toxins.

    Science.gov (United States)

    Hicks, Rickey P; Hartell, Mark G; Nichols, Daniel A; Bhattacharjee, Apurba K; van Hamont, John E; Skillman, Donald R

    2005-01-01

    The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population from the medical consequences of these weapons. In addition there are major health concerns associated with a pre-exposure mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria Bacillus anthracis. Anthrax will be addressed because of its similarity in both structure and mechanism of catalytic activity with botulinum toxin. The common feature of these three agents is that they exhibit their biological activity via toxin enzymatic hydrolysis of a specific bond in their respective substrate molecules. A brief introduction to the history of each of the biological warfare agents is presented followed by a discussion on the mechanisms of action of each at the molecular level, and a review of current potential inhibitors under investigation.

  19. The evaluation of clinical and laboratory findings of 63 inpatient with cutaneous anthrax: Characteristics of cutaneous anthrax in Turkey

    Directory of Open Access Journals (Sweden)

    Hatice Uce Özkol

    2014-12-01

    Full Text Available Background and Design: Despite a very uncommon disease in developed countries, cutaneous anthrax (CA is currently endemic in our countries. In this study, we aimed to bring out characteristic of anthrax of Turkey by comparing our results and the other CA reports in Turkey. Materials and Methods: Sixty three inpatients with CA between October 2009 and December 2012 were investigated retrospectively. All patients were diagnosed CA by clinical finding and/or microbiological examination. The demographic characteristics patient, routine tests, wound culture and gram staining results were recorded. Results were recorded on statistical program of SPSS 13.0 and were written using percent (%. Results: There were 63 inpatients (41 female (65.1%, 22 male (34.9%, mean age 35.9 years range10-83. Forty nine patients (77.8% had a history of contact with animals or animal product. Thirty-eight (60.3% and twenty-one (33.3% patients were found in the summer and fall season, respectively. Gram staining and culture were performed in 51 patients. Gram-positive bacilli were detected in 17 patients (33.3% by gram smear. Bacillus anthracis bacilli were produced in 11 patients (21.5% in cultures test. The lesions were mostly seen on the left hand (30.2%. Penicillin was most frequently preferred in treatment of CA (87.3%. Conclusion: CA is still endemic in Eastern Anatolia and continues to increase in recent years. Women living in the villages in which income is obtained from buying and selling of animals constitute the most important risk group. Preventive actions such as training of the risky society, vaccination of animals, and obstructing of illegal animal entries across the border, will reduce the incidence of CA.

  20. Meningoencephalitis due to anthrax: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Yildirim, Hanefi; Koc, Mustafa; Murat, Ayse [Firat University, Department of Radiology, Elazig (Turkey); Kabakus, Nimet; Incekoey Girgin, Feyza [Firat University, Department of Paediatric Neurology, Elazig (Turkey)

    2006-11-15

    Anthrax is primarily a disease of herbivores, but it also causes cutaneous, respiratory and gastrointestinal infections in humans. Bacillus anthracis is an uncommon cause of meningitis and generally produces a haemorrhagic meningoencephalitis. We present the CT and MR findings of anthrax meningoencephalitis due to the cutaneous form of anthrax in a 12-year-old boy. They showed focal intracerebral haemorrhage with leptomeningeal enhancement. (orig.)

  1. Human anthrax as a re-emerging disease.

    Science.gov (United States)

    Doganay, Mehmet; Demiraslan, Hayati

    2015-01-01

    Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

  2. Small molecule inhibitors of anthrax edema factor.

    Science.gov (United States)

    Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Thai, April; Cregar-Hernandez, Lynne; McKasson, Linda; O'Malley, Sean; Leppla, Stephen H; Johnson, Alan T

    2018-01-15

    Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Trimethyl Chitosan Nanoparticles Encapsulated Protective Antigen Protects the Mice Against Anthrax

    Directory of Open Access Journals (Sweden)

    Anshu Malik

    2018-03-01

    Full Text Available Anthrax is an era old deadly disease against which there are only two currently available licensed vaccines named anthrax vaccine adsorbed and precipitated (AVP. Though they can provide a protective immunity, their multiple side-effects owing to their ill-defined composition and presence of toxic proteins (LF and EF of Bacillus anthracis, the causative organism of anthrax, in the vaccine formulation makes their widespread use objectionable. Hence, an anthrax vaccine that contains well-defined and controlled components would be highly desirable. In this context, we have evaluated the potential of various vaccine formulations comprising of protective antigen (PA encapsulated trimethyl-chitosan nanoparticles (TMC-PA in conjunction with either CpG-C ODN 2395 (CpG or Poly I:C. Each formulation was administered via three different routes, viz., subcutaneous (SC, intramuscular (IM, and intraperitoneal in female BALB/c mice. Irrespective of the route of immunization, CpG or Poly I:C adjuvanted TMC-PA nanoparticles induced a significantly higher humoral response (total serum IgG and its isotypes viz., IgG1, IgG2a, and IgG2b, compared to their CpG or Poly I:C PA counterparts. This clearly demonstrates the synergistic behavior of CpG and Poly I:C with TMC nanoparticles. The adjuvant potential of TMC nanoparticles could be observed in all the three routes as the TMC-PA nanoparticles by themselves induced IgG titers (1–1.5 × 105 significantly higher than both CpG PA and Poly I:C PA groups (2–8 × 104. The effect of formulations on T-helper (Th cell development was assessed by quantifying the Th1-dependant (TNF-α, IFN-γ, and IL-2, Th2-dependant (IL-4, IL-6, and IL-10, and Th17-type (IL-17A cytokines. Adjuvanation with CpG and Poly I:C, the TMC-PA nanoparticles triggered a Th1 skewed immune response, as suggested by an increase in the levels of total IgG2a along with IFN-γ cytokine production. Interestingly, the TMC-PA group showed a Th2-biased

  4. Two anthrax cases with soft tissue infection, severe oedema and sepsis in Danish heroin users

    DEFF Research Database (Denmark)

    Russell, Lene; Pedersen, Michael; Jensen, Andreas V

    2013-01-01

    Anthrax had become extremely rare in Europe, but in 2010 an outbreak of anthrax among heroin users in Scotland increased awareness of contaminated heroin as a source of anthrax. We present the first two Danish cases of injectional anthrax and discuss the clinical presentations, which included both...

  5. Screen-printed fluorescent sensors for rapid and sensitive anthrax biomarker detection

    International Nuclear Information System (INIS)

    Lee, Inkyu; Oh, Wan-Kyu; Jang, Jyongsik

    2013-01-01

    Highlights: •We fabricated flexible anthrax sensors with a simple screen-printing method. •The sensors selectively detected B. anthracis biomarker. •The sensors provide the visible alarm against anthrax attack. -- Abstract: Since the 2001 anthrax attacks, efforts have focused on the development of an anthrax detector with rapid response and high selectivity and sensitivity. Here, we demonstrate a fluorescence sensor for detecting anthrax biomarker with high sensitivity and selectivity using a screen-printing method. A lanthanide–ethylenediamine tetraacetic acid complex was printed on a flexible polyethersulfone film. Screen-printing deposition of fluorescent detecting moieties produced fluorescent patterns that acted as a visual alarm against anthrax

  6. Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis

    National Research Council Canada - National Science Library

    Brittingham, Katherine C; Ruthel, Gordon; Panchal, Rekha G; Fuller, Claudette L; Ribot, Wilson J

    2005-01-01

    Phagocytosis of inhaled Bacillus anthracis spores and subsequent trafficking to lymph nodes are decisive events in the progression of inhaled anthrax because they initiate germination and dissemination of spores...

  7. [Anthrax meningoencephalitis: a case report and review of Turkish literature].

    Science.gov (United States)

    Metan, Gökhan; Uysal, Burcu; Coşkun, Ramazan; Perçin, Duygu; Doğanay, Mehmet

    2009-10-01

    The incidence of anthrax is decreasing in Turkey, however, it is still endemic in some regions of the country. Although central nervous system involvement is rare in cases with anthrax, high mortality rates are significant. Here, we report a 46-years old woman who was anthrax meningoencephalitis. The patient was from Yozgat located in Central Anatolia, Turkey. Her history revealed that following peeling the skin of sheeps and consuming their meat a week ago, a lesion developed in her left forearm and she had been treated with penicilin G with the diagnosis of cutaneous anthrax in a local health center. The patient was admitted to the emergency room of our hospital due to increased headache and loss of conciousness and diagnosed as anthrax meningitis. Crytallized penicilin G (24 MU/day IV) and vancomycin (2 g/day IV) were initiated. The macroscopy of cerebrospinal fluid (CSF) sample was haemorrhagic, white blood cell count was 40/mm3 (80% of neutrophil) and Gram staining of CSF yielded abundant gram-positive bacilli. The diagnosis was confirmed by the isolation of Bacillus anthracis from CSF culture. Although the isolate was susceptible to penicillin and dexamethasone was added to the treatment, the patient died. Review of the Turkish literature revealed seven cases of anthrax with central nervous system involvement between 1980-2008. One of the patients was an 11-years old boy and the others were adults aged between 19 and 64 years. The source of the infection was skin in four patients and inhalation in one patient. The most common findings in all of the patients were inhabitance in rural area, haemorrhagic CSF and loss of all patients despite appropriate antibiotic therapy. In conclusion, anthrax meningitis and meningoencephalitis should be considered in the differential diagnosis of haemorrhagic meningitis in areas where anthrax is endemic and high rate of mortality despite appropriate therapy should always be kept in mind.

  8. Effective antiprotease-antibiotic treatment of experimental anthrax

    OpenAIRE

    Popov, Serguei G; Popova, Taissia G; Hopkins, Svetlana; Weinstein, Raymond S; MacAfee, Rebecca; Fryxell, Karl J; Chandhoke, Vikas; Bailey, Charles; Alibek, Ken

    2005-01-01

    Abstract Background Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our un...

  9. Genetically modified anthrax lethal toxin safely delivers whole HIV protein antigens into the cytosol to induce T cell immunity

    Science.gov (United States)

    Lu, Yichen; Friedman, Rachel; Kushner, Nicholas; Doling, Amy; Thomas, Lawrence; Touzjian, Neal; Starnbach, Michael; Lieberman, Judy

    2000-07-01

    Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to the cytosol for antigen presentation to CD8 T cells. Vaccination with modified toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in mice. To evaluate whether large protein antigens can be used with this system, recombinant constructs encoding several HIV antigens up to 500 amino acids were produced. These candidate HIV vaccines are safe in animals and induce CD8 T cells in mice. Constructs encoding gag p24 and nef stimulate gag-specific CD4 proliferation and a secondary cytotoxic T lymphocyte response in HIV-infected donor peripheral blood mononuclear cells in vitro. These results lay the foundation for future clinical vaccine studies.

  10. A retrospective study on the epidemiology of anthrax, foot and mouth disease, haemorrhagic septicaemia, peste des petits ruminants and rabies in Bangladesh, 2010-2012.

    Directory of Open Access Journals (Sweden)

    Shankar P Mondal

    Full Text Available Anthrax, foot and mouth disease (FMD, haemorrhagic septicaemia (HS, peste des petits ruminants (PPR and rabies are considered to be endemic in Bangladesh. This retrospective study was conducted to understand the geographic and seasonal distribution of these major infectious diseases in livestock based on data collected through passive surveillance from 1 January 2010 to 31 December 2012. Data analysis for this period revealed 5,937 cases of anthrax, 300,333 of FMD, 13,436 of HS, 247,783 of PPR and 14,085 cases of dog bite/rabies. While diseases were reported in almost every district of the country, the highest frequency of occurrence corresponded to the susceptible livestock population in the respective districts. There was no significant difference in the disease occurrences between districts bordering India/Myanmar and non-border districts (p>0.05. Significantly higher (p<0.01 numbers of anthrax (84.5%, FMD (88.3%, HS (84.9% and dog bite/rabies (64.3% cases were reported in cattle than any other species. PPR cases were reported mostly (94.8% in goats with only isolated cases (5.2% in sheep. The diseases occur throughout the year with peak numbers reported during June through September and lowest during December through April, with significant differences (p<0.01 between the months. The annual usages of vaccines for anthrax, FMD, HS and PPR were only 7.31%, 0.61%, 0.84% and 11.59% of the susceptible livestock population, respectively. Prophylactic vaccination against rabies was 21.16% of cases. There were significant differences (p<0.01 in the administration of anthrax, FMD and HS vaccines between border and non-border districts, but not PPR or rabies vaccines. We recommend that surveillance and reporting of these diseases need to be improved throughout the country. Furthermore, all suspected clinical cases should be confirmed by laboratory examination. The findings of this study can be used in the formulation of more effective disease

  11. The use of anthrax and orthopox therapeutic antibodies from human origin in biodefense

    International Nuclear Information System (INIS)

    Stienstra, S.

    2009-01-01

    It is impossible to protect whole nations from the effects of bioterrorism by preventive vaccination; there are too many possible agents, costs would be exorbitantly high, and the health risks associated with complex mass vaccination programs would be unacceptable. Adequate protection, however, could be provided via a combination of rapid detection and diagnosis and the treatment of those exposed with drugs which would be beneficial in all stages of disease. Monoclonal antibodies, preferably from human origin to prevent severe complications, which neutralize or block the pathological effects of biological agents, are the optimal candidates to be deployed in case of biological warfare or a bioterrorist event. The human body is one of the better and most suitably equipped places for the generation of monoclonal antibodies which are to be used effectively in humans for treatment. Such antibodies will be of optimal physiological specificity, affinity, and pharmacological properties. In addition, the chances on severe adverse effects and cross-reactivity with human tissues will be slim. Therefore the human immune response is used by the Dutch company IQ Therapeutics, a spin-off of the Groningen University, as a basis for selecting the antibodies. People, immunised against or infected with the agent in question, donate blood cells voluntarily, which are used to generate fully human monoclonal antibodies. In this way effective therapeutics against the protective antigen (PA) and lethal factor (LF) toxin components of Bacillus anthracis are developed and currently antibodies against orthopox viruses are generated as well from donors, which have been immunized with vaccinia. Other projects are the development of therapeutic antibodies for MRSA (antibiotics resistant Staphylococcus aureus) and Enterococcus spp. Both human antibodies against the anthrax toxin components are efficacious in vitro and in pre- and post-exposure settings in mice and rabbits. The anti-LF antibody

  12. Tumor Targeting and Drug Delivery by Anthrax Toxin

    Directory of Open Access Journals (Sweden)

    Christopher Bachran

    2016-07-01

    Full Text Available Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  13. Tumor Targeting and Drug Delivery by Anthrax Toxin.

    Science.gov (United States)

    Bachran, Christopher; Leppla, Stephen H

    2016-07-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  14. Sverdlovsk Anthrax Outbreak: An Educational Case Study

    Science.gov (United States)

    Steele, S. J.; van der Vink, G.

    2002-05-01

    In April and May of 1979 an Anthrax epidemic broke out in the city of Sverdlovsk (now Ekaterinburg) in the former Soviet Union. Sixty-four people were reported to have died from the outbreak, although there is still debate concerning the actual number of victims. While Soviet officials initially attributed this outbreak to contaminated meat, the US Government maintained that the outbreak was due to a leakage from a biological weapons facility. We have created and implemented an undergraduate educational exercise based on the forensic analysis of this event. Students were provided case data of the victims, area satellite images and meteorological data. One goal of the exercise was for students to reconstruct the most probable scenario of events through valid inference based on the limited information and uncertainties associated with the data set. Another goal was to make students sensitive to issues of biological weapons and bioterrorism. The exercise was highly rated by students even before the events of September 11. There is a clear need to educate students, particularly in the sciences, to be aware of the signatures of terrorist activities. Evidence of terrorist activities is more likely to appear from unintended discoveries than from active intelligence gathering. We believe our national security can be enhanced by sensitizing those that monitor the natural environment to the signatures of terrorist activities through the types of educational exercises that we have developed.

  15. Serology and anthrax in humans, livestock and Etosha National Park wildlife.

    Science.gov (United States)

    Turnbull, P C; Doganay, M; Lindeque, P M; Aygen, B; McLaughlin, J

    1992-04-01

    Results are presented from a number of epidemiological studies using enzyme immunoassays (EIA) based on the purified anthrax toxin antigens, protective antigen, lethal factor and oedema factor. Studies on sera from a group of 62 human anthrax patients in Turkey and from cattle in Britain following two unrelated outbreaks of anthrax show that EIA using protective antigen can be a useful diagnostic aid and will detect subclinical infections in appropriate circumstances. A serological survey on wildlife in the Etosha National Park, Namibia, where anthrax is endemic, showed that naturally acquired anthrax-specific antibodies are rare in herbivores but common in carnivores; in carnivores, titres appear to reflect the prevalence of anthrax in their ranges. Problems, as yet unresolved, were encountered in studies on sera from pigs following an outbreak of anthrax on a farm in Wales. Clinical details, including treatment, of the human and one of the bovine outbreaks are summarized and discussed in relation to the serological findings.

  16. Tumor Targeting and Drug Delivery by Anthrax Toxin

    OpenAIRE

    Bachran, Christopher; Leppla, Stephen H.

    2016-01-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associ...

  17. Micromotors to capture and destroy anthrax simulant spores.

    Science.gov (United States)

    Orozco, Jahir; Pan, Guoqing; Sattayasamitsathit, Sirilak; Galarnyk, Michael; Wang, Joseph

    2015-03-07

    Towards addressing the need for detecting and eliminating biothreats, we describe a micromotor-based approach for screening, capturing, isolating and destroying anthrax simulant spores in a simple and rapid manner with minimal sample processing. The B. globilli antibody-functionalized micromotors can recognize, capture and transport B. globigii spores in environmental matrices, while showing non-interactions with excess of non-target bacteria. Efficient destruction of the anthrax simulant spores is demonstrated via the micromotor-induced mixing of a mild oxidizing solution. The new micromotor-based approach paves a way to dynamic multifunctional systems that rapidly recognize, isolate, capture and destroy biological threats.

  18. Growth medium for the rapid isolation and identification of anthrax

    Science.gov (United States)

    Kiel, Johnathan L.; Parker, Jill E.; Grubbs, Teri R.; Alls, John L.

    2000-07-01

    Anthrax has been recognized as a highly likely biological warfare or terrorist agent. The purpose of this work was to design a culture technique to rapidly isolate and identify `live' anthrax. In liquid or solid media form, 3AT medium (3-amino-L-tyrosine, the main ingredient) accelerated germination and growth of anthrax spores in 5 to 6 hours to a point expected at 18 to 24 hours with ordinary medium. During accelerated growth, standard definitive diagnostic tests such as sensitivity to lysis by penicillin or bacteriophage can be run. During this time, the bacteria synthesized a fluorescent and thermochemiluminescent polymer. Bacteria captured by specific antibody are, therefore, already labeled. Because living bacteria are required to generate the polymer, the test converts immunoassays for anthrax into viability assays. Furthermore, the polymer formation leads to the death of the vegetative form and non-viability of the spores produced in the medium. By altering the formulation of the medium, other microbes and even animal and human cells can be grown in it and labeled (including viruses grown in the animal or human cells).

  19. First Autochthonous Coinfected Anthrax in an Immunocompetent Patient

    Directory of Open Access Journals (Sweden)

    Parvaneh Afshar

    2015-01-01

    Full Text Available Cutaneous anthrax has a mortality rate of 20% if no antibacterial treatment is applied. The clinical manifestations of cutaneous anthrax are obviously striking, but coinfection may produce atypical lesions and mask the clinical manifestations and proper laboratory diagnosis. Anthrax is known to be more common in the Middle East and Iran is one of the countries in which the zoonotic form of anthrax may still be encountered. We report a case of a 19-years-old male who used to apply Venetian ceruse on his skin. Venetian ceruse (also known as Spirits of Saturn is an old cosmetic product used for skin whitening traditionally made from sheep’s spinal cord. The patient referred to the Referral Laboratory, Mazandaran University of Medical Sciences, Sari, Iran, with atypical dermatosis, pronounced pain, and oedema of the affected tissue. It was confirmed by both conventional and molecular analysis that culture was a mixture of Bacillus anthracis and Trichophyton interdigitale. The patient was initially treated with ceftriaxone (1000 mg/day for two weeks, gentamicin (1.5–2 mg/kg/day, terbinafine (200 mg/week for one month, and 1% clotrimazole cream (5 weeks two times per day which resulted in gradual improvement. No relapse could be detected after one-year follow-up. Anthrax infection might present a broader spectrum of symptoms than expected by clinicians. These unfamiliar characteristics may lead to delayed diagnosis, inadequate treatment, and higher mortality rate. Clinicians need to be aware of this issue in order to have successful management over this infection.

  20. Evaluation of the house fly Musca domestica as a mechanical vector for an anthrax.

    Directory of Open Access Journals (Sweden)

    Antonio Fasanella

    Full Text Available Anthrax is a disease of human beings and animals caused by the encapsulated, spore-forming, Bacillus anthracis. The potential role of insects in the spread of B. anthracis to humans and domestic animals during an anthrax outbreak has been confirmed by many studies. Among insect vectors, the house fly Musca domestica is considered a potential agent for disease transmission. In this study, laboratory-bred specimens of Musca domestica were infected by feeding on anthrax-infected rabbit carcass or anthrax contaminated blood, and the presence of anthrax spores in their spots (faeces and vomitus was microbiologically monitored. It was also evaluated if the anthrax spores were able to germinate and replicate in the gut content of insects. These results confirmed the role of insects in spreading anthrax infection. This role, although not major, given the huge size of fly populations often associated with anthrax epidemics in domestic animals, cannot be neglected from an epidemiological point of view and suggest that fly control should be considered as part of anthrax control programs.

  1. Ecological suitability modeling for anthrax in the Kruger National Park, South Africa.

    Directory of Open Access Journals (Sweden)

    Pieter Johan Steenkamp

    Full Text Available The spores of the soil-borne bacterium, Bacillus anthracis, which causes anthrax are highly resistant to adverse environmental conditions. Under ideal conditions, anthrax spores can survive for many years in the soil. Anthrax is known to be endemic in the northern part of Kruger National Park (KNP in South Africa (SA, with occasional epidemics spreading southward. The aim of this study was to identify and map areas that are ecologically suitable for the harboring of B. anthracis spores within the KNP. Anthrax surveillance data and selected environmental variables were used as inputs to the maximum entropy (Maxent species distribution modeling method. Anthrax positive carcasses from 1988-2011 in KNP (n = 597 and a total of 40 environmental variables were used to predict and evaluate their relative contribution to suitability for anthrax occurrence in KNP. The environmental variables that contributed the most to the occurrence of anthrax were soil type, normalized difference vegetation index (NDVI and precipitation. Apart from the endemic Pafuri region, several other areas within KNP were classified as ecologically suitable. The outputs of this study could guide future surveillance efforts to focus on predicted suitable areas for anthrax, since the KNP currently uses passive surveillance to detect anthrax outbreaks.

  2. Integrated MOSFET-Embedded-Cantilever-Based Biosensor Characteristic for Detection of Anthrax Simulant

    Energy Technology Data Exchange (ETDEWEB)

    Mostafa, Salwa [University of Tennessee, Knoxville (UTK); Lee, Ida [ORNL; Islam, Syed K [University of Tennessee, Knoxville (UTK); Eliza, Sazia A. [University of Tennessee, Knoxville (UTK); Shekhawat, Gajendra [Northwestern University, Evanston; Dravid, Vinayak [Northwestern University, Evanston; Tulip, Fahmida S [ORNL

    2011-01-01

    In this work, MOSFET-embedded cantilevers are configured as microbial sensors for detection of anthrax simulants, Bacillus thuringiensis. Anthrax simulants attached to the chemically treated gold-coated cantilever cause changes in the MOSFET drain current due to the bending of the cantilever which indicates the detection of anthrax simulant. Electrical properties of the anthrax simulant are also responsible for the change in the drain current. The test results suggest a detection range of 10 L of stimulant test solution (a suspension population of 1.3 107 colony-forming units/mL diluted in 40% ethanol and 60% deionized water) with a linear response of 31 A/ L.

  3. [Anthrax in the canton of Zurich between 1878 and 2005].

    Science.gov (United States)

    Brandes Ammann, A; Brandl, H

    2007-07-01

    Historical records reporting cases of animal anthrax in the canton of Zurich between 1878 and 2005 were analysed on the level of political communities regarding occurrence and number of cases, animals affected, and number of communities affected. Data were correlated with industrial activities (tanning, wool and horse hair processing) in a community and to the prevailing meteorological conditions. A total of 830 cases of animal anthrax has been recorded in 140 of 171 communities. Occurrence correlated with industrial activities in a community such as companies handling potentially contaminated materials (hides, fur, wool, hair, meat, or bone meal). The influence of wool processing companies (P = 0. 004) and tanneries (P = 0. 032) was significant whereas horse hair processing had no effect. However, a statistical relationship between the number of cases reported and meteorological data (rainfall, mean temperature) was not found.

  4. [Anthrax meningoencephalitis: a case following a cutaneous lesion in Morocco].

    Science.gov (United States)

    Ziadi, A; Hachimi, A; Soraa, N; Tassi, N; Nejmi, H; Elkhayari, M; Samkaoui, M A

    2014-05-01

    Anthrax meningoencephalitis is very rare especially following skin location. We report a case of meningoencephalitis secondary to skin lesion. The diagnosis is based on clinical presentation and confirmed by microbiological tests. Its evolution remains fatal despite aggressive resuscitation. Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  5. Effective antiprotease-antibiotic treatment of experimental anthrax

    Directory of Open Access Journals (Sweden)

    MacAfee Rebecca

    2005-04-01

    Full Text Available Abstract Background Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our understanding of anthrax molecular pathology and the most prominent clinical features of the infectious process we undertook bioinformatic and experimental analyses of potential proteolytic virulence factors of B. anthracis distinct from lethal toxin. Methods Secreted proteins (other than lethal and edema toxins produced by B. anthracis were tested for tissue-damaging activity and toxicity in mice. Chemical protease inhibitors and rabbit immune sera raised against B. anthracis proteases were used to treat mice challenged with B. anthracis (Sterne spores. Results B. anthracis strain delta Ames (pXO1-, pXO2- producing no lethal and edema toxins secrets a number of metalloprotease virulence factors upon cultivation under aerobic conditions, including those with hemorrhagic, caseinolytic and collagenolytic activities, belonging to M4 and M9 thermolysin and bacterial collagenase families, respectively. These factors are directly toxic to DBA/2 mice upon intratracheal administration at 0.5 mg/kg and higher doses. Chemical protease inhibitors (phosphoramidon and 1, 10-phenanthroline, as well as immune sera against M4 and M9 proteases of B. anthracis, were used to treat mice challenged with B. anthracis (Sterne spores. These substances demonstrate a substantial protective efficacy in combination with ciprofloxacin therapy initiated as late as 48 h post spore challenge, compared to the antibiotic alone. Conclusion Secreted proteolytic enzymes are important pathogenic

  6. America’s Food: Does Anthrax Pose A Threat?

    Science.gov (United States)

    2002-04-01

    a 1996 JAMA article, “Unexplained Severe Illness Possibly Associated with Consumption of Kombucha Tea - Iowa 1995.”13 For clarification, the... Kombucha “mush- room” is a “ symbiotic colony of several species of yeast and bacteria that are bound to- gether by a surrounding membrane.”14 Dr. Sadjadi...described an outbreak in Iran of cuta- 9 neous anthrax related to the Kombucha mushroom. In 1996 in a village on the outskirts of Tehran, 20 people

  7. [Efficacy of enterocin S760 in treatment of mice with anthrax infection due to Bacillus anthracis M-71].

    Science.gov (United States)

    Svetoch, E A; Borzilov, A I; Eruslanov, B V; Korobova, O V; Kombarova, T I; Levchuk, V P; Teĭmurazov, M G; Stepanshin, Iu G; Marinin, L I; Diatlov, I A

    2011-01-01

    The therapeutic efficacy of enterocin S760, a broad spectrum antimicrobial peptide produced by Enterococcus faecium LWP760 was tested on mice infected with Bacillus anthracis M-71 to induce anthrax (second Tsenkovsky's vaccine). Intraperitoneal four-, two- or one-fold administration of the peptide in a dose of 25 mg/kg for 10 days for prophylactic (1 hour after the contamination) and therapeutic (24 hours after the contamination) purposes prevented or cured the infection in 90-100% of the mice versus the 100-percent lethality in the control (untreated animals). The antimicrobial activity of enterocin S760 against B. anthracis M-71 in vivo correlated with activity in vitro. Enterocin S760 is considered a novel promising antimicrobial for the treatment of grampositive and gramnegative infections.

  8. Dismantling the Taboo against Vaccines in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maurizio de Martino

    2016-06-01

    Full Text Available Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

  9. DUST-BATHING BEHAVIORS OF AFRICAN HERBIVORES AND THE POTENTIAL RISK OF INHALATIONAL ANTHRAX.

    Science.gov (United States)

    Barandongo, Zoe R; Mfune, John K E; Turner, Wendy C

    2018-01-01

    :  Anthrax in herbivorous wildlife and livestock is generally assumed to be transmitted via ingestion or inhalation of Bacillus anthracis spores. Although recent studies have highlighted the importance of the ingestion route for anthrax transmission, little is known about the inhalational route in natural systems. Dust bathing could aerosolize soilborne pathogens such as B. anthracis, exposing dust-bathing individuals to inhalational infections. We investigated the potential role of dust bathing in the transmission of inhalational anthrax to herbivorous wildlife in Etosha National Park, Namibia, an area with endemic seasonal anthrax outbreaks. We 1) cultured soils from dust-bathing sites for the presence and concentration of B. anthracis spores, 2) monitored anthrax carcass sites, the locations with the highest B. anthracis concentrations, for evidence of dust bathing, including a site where a zebra died of anthrax on a large dust bath, and 3) characterized the ecology and seasonality of dust bathing in plains zebra ( Equus quagga), blue wildebeest ( Connochaetes taurinus), and African savanna elephant ( Loxodonta africana) using a combination of motion-sensing camera traps and direct observations. Only two out of 83 dust-bath soils were positive for B. anthracis, both with low spore concentrations (≤20 colony-forming units per gram). We also detected no evidence of dust baths occurring at anthrax carcass sites, perhaps due to carcass-induced changes in soil composition that may deter dust bathing. Finally, despite observing some seasonal variation in dust bathing, preliminary evidence suggests that the seasonality of dust bathing and anthrax mortalities are not correlated. Thus, although dust bathing creates a dramatic cloud of aerosolized soil around an individual, our microbiologic, ecologic, and behavioral results in concert demonstrate that dust bathing is highly unlikely to transmit inhalational anthrax infections.

  10. Mapping the Distribution of Anthrax in Mainland China, 2005-2013.

    Directory of Open Access Journals (Sweden)

    Wan-Jun Chen

    2016-04-01

    Full Text Available Anthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland China. Despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood.Using the national surveillance data of human and livestock anthrax from 2005 to 2013, we conducted a retrospective epidemiological study and risk assessment of anthrax in mainland China. The potential determinants for the temporal and spatial distributions of human anthrax were also explored. We found that the majority of human anthrax cases were located in six provinces in western and northeastern China, and five clustering areas with higher incidences were identified. The disease mostly peaked in July or August, and males aged 30-49 years had higher incidence than other subgroups. Monthly incidence of human anthrax was positively correlated with monthly average temperature, relative humidity and monthly accumulative rainfall with lags of 0-2 months. A boosted regression trees (BRT model at the county level reveals that densities of cattle, sheep and human, coverage of meadow, coverage of typical grassland, elevation, coverage of topsoil with pH > 6.1, concentration of organic carbon in topsoil, and the meteorological factors have contributed substantially to the spatial distribution of the disease. The model-predicted probability of occurrence of human cases in mainland China was mapped at the county level.Anthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections.

  11. Defining Moments in MMWR History: CDC's Response to Intentional Release of Anthrax - 2001

    Centers for Disease Control (CDC) Podcasts

    On October 4, 2001, shortly after the September 11 attacks in New York City and Washington, DC, the Palm Beach County Health Department, the Florida State Department of Health, and CDC reported a case of anthrax in a 63-year-old man from Florida. This case was first reported in MMWR and marked the beginning of a series of anthrax cases that resulted from intentional delivery of Bacillus anthracis spores sent through the mail. In this podcast, Dr. Sherif Zaki recalls CDC's investigation and response to the anthrax attacks.

  12. Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

    Directory of Open Access Journals (Sweden)

    Paul Keim

    2015-11-01

    Lay Person Interpretation: Injectional anthrax has been plaguing heroin drug users across Europe for more than 10 years. In order to better understand this outbreak, we assessed genomic relationships of all available injectional anthrax strains from four countries spanning a >12 year period. Very few differences were identified using genome-based analysis, but these differentiated the isolates into two distinct clusters. This strongly supports a hypothesis of at least two separate anthrax spore contamination events perhaps during the drug production processes. Identification of two events would not have been possible from standard epidemiological analysis. These comprehensive data will be invaluable for classifying future injectional anthrax isolates and for future geographic attribution.

  13. Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest.

    Science.gov (United States)

    Hoffmann, Constanze; Zimmermann, Fee; Biek, Roman; Kuehl, Hjalmar; Nowak, Kathrin; Mundry, Roger; Agbor, Anthony; Angedakin, Samuel; Arandjelovic, Mimi; Blankenburg, Anja; Brazolla, Gregory; Corogenes, Katherine; Couacy-Hymann, Emmanuel; Deschner, Tobias; Dieguez, Paula; Dierks, Karsten; Düx, Ariane; Dupke, Susann; Eshuis, Henk; Formenty, Pierre; Yuh, Yisa Ginath; Goedmakers, Annemarie; Gogarten, Jan F; Granjon, Anne-Céline; McGraw, Scott; Grunow, Roland; Hart, John; Jones, Sorrel; Junker, Jessica; Kiang, John; Langergraber, Kevin; Lapuente, Juan; Lee, Kevin; Leendertz, Siv Aina; Léguillon, Floraine; Leinert, Vera; Löhrich, Therese; Marrocoli, Sergio; Mätz-Rensing, Kerstin; Meier, Amelia; Merkel, Kevin; Metzger, Sonja; Murai, Mizuki; Niedorf, Svenja; De Nys, Hélène; Sachse, Andreas; van Schijndel, Joost; Thiesen, Ulla; Ton, Els; Wu, Doris; Wieler, Lothar H; Boesch, Christophe; Klee, Silke R; Wittig, Roman M; Calvignac-Spencer, Sébastien; Leendertz, Fabian H

    2017-08-02

    Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.

  14. Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax

    National Research Council Canada - National Science Library

    Heine, H. S; Bassett, J; Miller, L; Bassett, A; Ivins, B. E; Lehous, D; Arhin, F. F; Parr, Jr., T. R; Moeck, G

    2008-01-01

    The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days...

  15. Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest

    Science.gov (United States)

    Hoffmann, Constanze; Zimmermann, Fee; Biek, Roman; Kuehl, Hjalmar; Nowak, Kathrin; Mundry, Roger; Agbor, Anthony; Angedakin, Samuel; Arandjelovic, Mimi; Blankenburg, Anja; Brazolla, Gregory; Corogenes, Katherine; Couacy-Hymann, Emmanuel; Deschner, Tobias; Dieguez, Paula; Dierks, Karsten; Düx, Ariane; Dupke, Susann; Eshuis, Henk; Formenty, Pierre; Yuh, Yisa Ginath; Goedmakers, Annemarie; Gogarten, Jan F.; Granjon, Anne-Céline; McGraw, Scott; Grunow, Roland; Hart, John; Jones, Sorrel; Junker, Jessica; Kiang, John; Langergraber, Kevin; Lapuente, Juan; Lee, Kevin; Leendertz, Siv Aina; Léguillon, Floraine; Leinert, Vera; Löhrich, Therese; Marrocoli, Sergio; Mätz-Rensing, Kerstin; Meier, Amelia; Merkel, Kevin; Metzger, Sonja; Murai, Mizuki; Niedorf, Svenja; de Nys, Hélène; Sachse, Andreas; van Schijndel, Joost; Thiesen, Ulla; Ton, Els; Wu, Doris; Wieler, Lothar H.; Boesch, Christophe; Klee, Silke R.; Wittig, Roman M.; Calvignac-Spencer, Sébastien; Leendertz, Fabian H.

    2017-08-01

    Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.

  16. Antibodies to Anthrax Toxin in Humans and Guinea Pigs and Their Relevance to Protective Immunity

    National Research Council Canada - National Science Library

    Turnbull, P

    1988-01-01

    ... stimulation of more than just production of antibody to PA. Titers to the three components in sera of individuals with histories of clinically diagnosed anthrax as well as from human vaccinees are included in the report.

  17. Soil geochemical parameters influencing the spatial distribution of anthrax in Northwest Minnesota, USA

    International Nuclear Information System (INIS)

    Nath, Samuel; Dere, Ashlee

    2016-01-01

    Bacillus anthracis is the pathogenic bacterium that causes anthrax, which dwells in soils as highly resilient endospores. B. anthracis spore viability in soil is dependent upon environmental conditions, but the soil properties necessary for spore survival are unclear. In this study we used a range of soil geochemical and physical parameters to predict the spatial distribution of B. anthracis in northwest Minnesota, where 64 cases of anthrax in livestock were reported from 2000 to 2013. Two modeling approaches at different spatial scales were used to identify the soil conditions most correlated to known anthrax cases using both statewide and locally collected soil data. Ecological niche models were constructed using the Maximum Entropy (Maxent) approach and included 11 soil parameters as environmental inputs and recorded anthrax cases as known presences. One ecological niche model used soil data and anthrax presences for the entire state while a second model used locally sampled soil data (n = 125) and a subset of anthrax presences, providing a test of spatial scale. In addition, simple logistic regression models using the localized soil data served as an independent measure of variable importance. Maxent model results indicate that at a statewide level, soil calcium and magnesium concentrations, soil pH, and sand content are the most important properties for predicting soil suitability for B. anthracis while at the local level, clay and sand content along with phosphorous and strontium concentrations are most important. These results also show that the spatial scale of analysis is important when considering soil parameters most important for B. anthracis spores. For example, at a broad scale, B. anthracis spores may require Ca-rich soils and an alkaline pH, but may also concentrate in microenvironments with high Sr concentrations. The study is also one of the first ecological niche models that demonstrates the major importance of soil texture for defining

  18. Use of the mice passive protection test to evaluate the humoral response in goats vaccinated with Sterne 34F2 live spore vaccine.

    Science.gov (United States)

    Phaswana, P H; Ndumnego, O C; Koehler, S M; Beyer, W; Crafford, J E; van Heerden, H

    2017-09-07

    The Sterne live spore vaccine (34F2) is the most widely used veterinary vaccine against anthrax in animals. Antibody responses to several antigens of Bacillus anthracis have been described with a large focus on those against protective antigen (PA). The focus of this study was to evaluate the protective humoral immune response induced by the live spore anthrax vaccine in goats. Boer goats vaccinated twice (week 0 and week 12) with the Sterne live spore vaccine and naive goats were used to monitor the anti-PA and toxin neutralizing antibodies at week 4 and week 17 (after the second vaccine dose) post vaccination. A/J mice were passively immunized with different dilutions of sera from immune and naive goats and then challenged with spores of B. anthracis strain 34F2 to determine the protective capacity of the goat sera. The goat anti-PA ELISA titres indicated significant sero-conversion at week 17 after the second doses of vaccine (p = 0.009). Mice receiving undiluted sera from goats given two doses of vaccine (twice immunized) showed the highest protection (86%) with only 20% of mice receiving 1:1000 diluted sera surviving lethal challenge. The in vitro toxin neutralization assay (TNA) titres correlated to protection of passively immunized A/J mice against lethal infection with the vaccine strain Sterne 34F2 spores using immune goat sera up to a 1:10 dilution (r s  ≥ 0.522, p = 0.046). This study suggests that the passive mouse protection model could be potentially used to evaluate the protective immune response in livestock animals vaccinated with the current live vaccine and new vaccines.

  19. Cutaneous anthrax in the northeast of Iran: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Mohsen Karbalaei Zadeh Babaki

    2018-02-01

    Full Text Available Bacillus anthracis is an aerobic, gram-positive, and spore-forming Bacillus species. The most common form of anthrax infection is the cutaneous form. The infection usually develops several days after exposure to products of infected animals and manifest as black sore with severe swelling on the skin.A 52-year-old female with a black and swollen lesion on her index finger presented to Ghaem Hospital, Mashhad, Iran, in October 2015. Biopsy and swab culture were performed immediately. Cutaneous anthrax was characterized by microscopic examination of B. anthracis spore using Gram staining. The patient was then treated with antibiotics after diagnosis.According to the reports of Provincial Health Center of Khorasan Razavi, northeast of Iran, no cases of anthrax have been reported in humans since 2013. There were neither occupational risk factors, nor any routine predisposing factors for acquiring anthrax in this woman. Although this patient is the first case reported with cutaneous anthrax since the past three years, two cases of sheep anthrax have been reported in Khorasan Razavi Province during 2013-2015. This patient had a history of contact with the skull of a slaughtered sheep. The patient was treated after making correct and rapid diagnosis and sufficient antibiotic therapy.

  20. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    OpenAIRE

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-01-01

    Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

  1. The Effects of Anthrax Lethal Toxin on Host Barrier Function

    Directory of Open Access Journals (Sweden)

    David M. Frucht

    2011-06-01

    Full Text Available The pathological actions of anthrax toxin require the activities of its edema factor (EF and lethal factor (LF enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA. LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs, but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.

  2. Anthrax Cases Associated with Animal-Hair Shaving Brushes.

    Science.gov (United States)

    Szablewski, Christine M; Hendricks, Kate; Bower, William A; Shadomy, Sean V; Hupert, Nathaniel

    2017-05-01

    During the First World War, anthrax cases in the United States and England increased greatly and seemed to be associated with use of new shaving brushes. Further investigation revealed that the source material and origin of shaving brushes had changed during the war. Cheap brushes of imported horsehair were being made to look like the preferred badger-hair brushes. Unfortunately, some of these brushes were not effectively disinfected and brought with them a nasty stowaway: Bacillus anthracis. A review of outbreak summaries, surveillance data, and case reports indicated that these cases originated from the use of ineffectively disinfected animal-hair shaving brushes. This historical information is relevant to current public health practice because renewed interest in vintage and animal-hair shaving brushes has been seen in popular culture. This information should help healthcare providers and public health officials answer questions on this topic.

  3. Temporal dynamics in microbial soil communities at anthrax carcass sites.

    Science.gov (United States)

    Valseth, Karoline; Nesbø, Camilla L; Easterday, W Ryan; Turner, Wendy C; Olsen, Jaran S; Stenseth, Nils Chr; Haverkamp, Thomas H A

    2017-09-26

    Anthrax is a globally distributed disease affecting primarily herbivorous mammals. It is caused by the soil-dwelling and spore-forming bacterium Bacillus anthracis. The dormant B. anthracis spores become vegetative after ingestion by grazing mammals. After killing the host, B. anthracis cells return to the soil where they sporulate, completing the lifecycle of the bacterium. Here we present the first study describing temporal microbial soil community changes in Etosha National Park, Namibia, after decomposition of two plains zebra (Equus quagga) anthrax carcasses. To circumvent state-associated-challenges (i.e. vegetative cells/spores) we monitored B. anthracis throughout the period using cultivation, qPCR and shotgun metagenomic sequencing. The combined results suggest that abundance estimation of spore-forming bacteria in their natural habitat by DNA-based approaches alone is insufficient due to poor recovery of DNA from spores. However, our combined approached allowed us to follow B. anthracis population dynamics (vegetative cells and spores) in the soil, along with closely related organisms from the B. cereus group, despite their high sequence similarity. Vegetative B. anthracis abundance peaked early in the time-series and then dropped when cells either sporulated or died. The time-series revealed that after carcass deposition, the typical semi-arid soil community (e.g. Frankiales and Rhizobiales species) becomes temporarily dominated by the orders Bacillales and Pseudomonadales, known to contain plant growth-promoting species. Our work indicates that complementing DNA based approaches with cultivation may give a more complete picture of the ecology of spore forming pathogens. Furthermore, the results suggests that the increased vegetation biomass production found at carcass sites is due to both added nutrients and the proliferation of microbial taxa that can be beneficial for plant growth. Thus, future B. anthracis transmission events at carcass sites may be

  4. In vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins

    International Nuclear Information System (INIS)

    Dadachova, Ekaterina; Rivera, Johanna; Revskaya, Ekaterina; Nakouzi, Antonio; Cahill, Sean M.; Blumenstein, Michael; Xiao, Hui; Rykunov, Dmitry; Casadevall, Arturo

    2008-01-01

    Introduction: There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), edema factor (EF) and protective antigen (PA) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. Availability of toxins labeled with imageable radioisotopes would allow to demonstrate their tissue distribution after intravenous injection at toxin concentration that are below pharmacologically significant to avoid masking by toxic effects. Methods: LF, EF and PA were radiolabeled with 188 Re and 99m Tc, and their performance in vitro was evaluated by macrophages and Chinese hamster ovary cells toxicity assays and by binding to macrophages. Scintigraphic imaging and biodistribution of intravenously (IV) injected 99m Tc-and 123 I-labeled toxins was performed in BALB/c mice. Results: Radiolabeled toxins preserved their biological activity. Scatchard-type analysis of the binding of radiolabeled PA to the J774.16 macrophage-like cells revealed 6.6x10 4 binding sites per cell with a dissociation constant of 6.7 nM. Comparative scintigraphic imaging of mice injected intravenously with either 99m Tc-or 123 I-labeled PA, EF and LF toxins demonstrated similar biodistribution patterns with early localization of radioactivity in the liver, spleen, intestines and excretion through kidneys. The finding of renal excretion shortly after IV injection strongly suggests that toxins are rapidly degraded which could contribute to the variability of mouse toxigenic assays. Biodistribution studies confirmed that all three toxins concentrated in the liver and the presence of high levels of radioactivity again implied rapid degradation in vivo. Conclusions: The availability of 188 Re and 99m Tc-labeled PA, LF and EF toxins allowed us to

  5. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): anthrax

    DEFF Research Database (Denmark)

    EFSA Panel on Animal Health and Welfare; More, Simon J.; Bøtner, Anette

    2017-01-01

    Anthrax has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on the eligibility of anthrax to be listed, Article 9 for the categorisation of anthrax according to disease prevention and control rul...... species to be listed for anthrax according to Article 8(3) are several species of mammals, birds and reptiles, and susceptible herbivores and pigs as reservoir....

  6. Historical evolution of human anthrax from occupational disease to potentially global threat as bioweapon.

    Science.gov (United States)

    D'Amelio, Enrico; Gentile, Bernardina; Lista, Florigio; D'Amelio, Raffaele

    2015-12-01

    Anthrax is caused by Bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. However, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, B. anthracis has been considered the most serious bioterrorism agent for a long time. During the last century anthrax evolved from limited natural disease to potentially global threat if used as bioweapon. Several factors may mitigate the consequences of an anthrax attack, including 1. the capability to promptly recognize and manage the illness and its public health consequences; 2. the limitation of secondary contamination risk through an appropriate decontamination; and 3. the evolution of genotyping methods (for microbes characterization at high resolution level) that can influence the course and/or focus of investigations, impacting the response of the government to an attack. A PubMed search has been done using the key words “bioterrorism anthrax”. Over one thousand papers have been screened and the most significant examined to present a comprehensive literature review in order to discuss the current knowledge and strategies in preparedness for a possible deliberate release of B. anthracis spores and to indicate the most current and complete documents in which to deepen. The comprehensive analysis of the two most relevant unnatural anthrax release events, Sverdlovsk in the former Soviet Union (1979) and the contaminated letters in the USA (2001), shows that inhalational anthrax may easily and cheaply be spread resulting in serious consequences. The damage caused by an anthrax attack can be limited if public health organization, first responders, researchers and investigators will be able to promptly manage anthrax cases and use new technologies for decontamination methods and in forensic microbiology.

  7. Monte Carlo N-particle simulation of neutron-based sterilisation of anthrax contamination.

    Science.gov (United States)

    Liu, B; Xu, J; Liu, T; Ouyang, X

    2012-10-01

    To simulate the neutron-based sterilisation of anthrax contamination by Monte Carlo N-particle (MCNP) 4C code. Neutrons are elementary particles that have no charge. They are 20 times more effective than electrons or γ-rays in killing anthrax spores on surfaces and inside closed containers. Neutrons emitted from a (252)Cf neutron source are in the 100 keV to 2 MeV energy range. A 2.5 MeV D-D neutron generator can create neutrons at up to 10(13) n s(-1) with current technology. All these enable an effective and low-cost method of killing anthrax spores. There is no effect on neutron energy deposition on the anthrax sample when using a reflector that is thicker than its saturation thickness. Among all three reflecting materials tested in the MCNP simulation, paraffin is the best because it has the thinnest saturation thickness and is easy to machine. The MCNP radiation dose and fluence simulation calculation also showed that the MCNP-simulated neutron fluence that is needed to kill the anthrax spores agrees with previous analytical estimations very well. The MCNP simulation indicates that a 10 min neutron irradiation from a 0.5 g (252)Cf neutron source or a 1 min neutron irradiation from a 2.5 MeV D-D neutron generator may kill all anthrax spores in a sample. This is a promising result because a 2.5 MeV D-D neutron generator output >10(13) n s(-1) should be attainable in the near future. This indicates that we could use a D-D neutron generator to sterilise anthrax contamination within several seconds.

  8. Vaccines (immunizations) - overview

    Science.gov (United States)

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

  9. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

    Science.gov (United States)

    Ascough, Stephanie; Ingram, Rebecca J; Chu, Karen K; Reynolds, Catherine J; Musson, Julie A; Doganay, Mehmet; Metan, Gökhan; Ozkul, Yusuf; Baillie, Les; Sriskandan, Shiranee; Moore, Stephen J; Gallagher, Theresa B; Dyson, Hugh; Williamson, E Diane; Robinson, John H; Maillere, Bernard; Boyton, Rosemary J; Altmann, Daniel M

    2014-05-01

    Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  10. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    International Nuclear Information System (INIS)

    Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

    2014-01-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  11. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  12. Tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors.

    Directory of Open Access Journals (Sweden)

    Chenguang Cai

    Full Text Available Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA, lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8 and capillary morphogenesis protein-2 (CMG2 can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA domain of CMG2 (sCMG2, have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8 was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs.

  13. The Disulfide Bond Cys255-Cys279 in the Immunoglobulin-Like Domain of Anthrax Toxin Receptor 2 Is Required for Membrane Insertion of Anthrax Protective Antigen Pore.

    Directory of Open Access Journals (Sweden)

    Pedro Jacquez

    Full Text Available Anthrax toxin receptors act as molecular clamps or switches that control anthrax toxin entry, pH-dependent pore formation, and translocation of enzymatic moieties across the endosomal membranes. We previously reported that reduction of the disulfide bonds in the immunoglobulin-like (Ig domain of the anthrax toxin receptor 2 (ANTXR2 inhibited the function of the protective antigen (PA pore. In the present study, the disulfide linkage in the Ig domain was identified as Cys255-Cys279 and Cys230-Cys315. Specific disulfide bond deletion mutants were achieved by replacing Cys residues with Ala residues. Deletion of the disulfide bond C255-C279, but not C230-C315, inhibited the PA pore-induced release of the fluorescence dyes from the liposomes, suggesting that C255-C279 is essential for PA pore function. Furthermore, we found that deletion of C255-C279 did not affect PA prepore-to-pore conversion, but inhibited PA pore membrane insertion by trapping the PA membrane-inserting loops in proteinaceous hydrophobic pockets. Fluorescence spectra of Trp59, a residue adjacent to the PA-binding motif in von Willebrand factor A (VWA domain of ANTXR2, showed that deletion of C255-C279 resulted in a significant conformational change on the receptor ectodomain. The disulfide deletion-induced conformational change on the VWA domain was further confirmed by single-particle 3D reconstruction of the negatively stained PA-receptor heptameric complexes. Together, the biochemical and structural data obtained in this study provides a mechanistic insight into the role of the receptor disulfide bond C255-C279 in anthrax toxin action. Manipulation of the redox states of the receptor, specifically targeting to C255-C279, may become a novel strategy to treat anthrax.

  14. Potent antitumor activity of a urokinase-activated engineered anthrax toxin

    Science.gov (United States)

    Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.

    2003-01-01

    The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

  15. Evaluation of cutaneous anthrax cases during an outbreak in the east region of Turkey.

    Science.gov (United States)

    Kural Ünüvar, Esra; Akgün Karapınar, Deniz Bahar; Dizen Namdar, Nazlı

    2016-11-17

    Anthrax is a zoonotic infection caused by Bacillus anthracis. We aimed to retrospectively evaluate cutaneous anthrax cases that occurred during an outbreak in eastern Turkey (Hakkari-Yüksekova), where people mostly earn their living from animal husbandry. Forty-six cutaneous anthrax patients that were admitted to the hospital during a very short duration of 3 months (June-August 2011) were evaluated. Out of 46 patients, 27 (52%) were women and 19 (48%) were men. The mean age was 37 ± 13 years. The distribution of occupations was 1 butcher, 1 cook, 5 farmers, 27 housewives, 11 shepherds, and 1 teacher. Multiple lesions were seen in 7 patients (15%) and the rest of the patients had only 1 lesion. We observed significant clinical differences among the cases and noted which particular symptoms were associated with the various skin lesions. We treated our patients with intramuscular procaine penicillin or oral ciprofloxacin/doxycycline. Anthrax is an important health problem that can cause lethal outbreaks. Therefore, one should think about anthrax when faced with a patient with history of animal contact that has a painless ulcer with edema and/or vesicles, especially in endemic countries like Turkey.

  16. Anthrax Sampling and Decontamination: Technology Trade-Offs

    Energy Technology Data Exchange (ETDEWEB)

    Price, Phillip N.; Hamachi, Kristina; McWilliams, Jennifer; Sohn, Michael D.

    2008-09-12

    The goal of this project was to answer the following questions concerning response to a future anthrax release (or suspected release) in a building: 1. Based on past experience, what rules of thumb can be determined concerning: (a) the amount of sampling that may be needed to determine the extent of contamination within a given building; (b) what portions of a building should be sampled; (c) the cost per square foot to decontaminate a given type of building using a given method; (d) the time required to prepare for, and perform, decontamination; (e) the effectiveness of a given decontamination method in a given type of building? 2. Based on past experience, what resources will be spent on evaluating the extent of contamination, performing decontamination, and assessing the effectiveness of the decontamination in abuilding of a given type and size? 3. What are the trade-offs between cost, time, and effectiveness for the various sampling plans, sampling methods, and decontamination methods that have been used in the past?

  17. Naturally acquired anthrax antibodies in a cheetah (Acinonyx jubatus) in Botswana.

    Science.gov (United States)

    Good, Kyle M; Houser, Annmarie; Arntzen, Lorraine; Turnbull, Peter C B

    2008-07-01

    An outbreak of anthrax in the Jwana Game Reserve in Jwaneng, Botswana, was first observed when three cheetahs (Acinonyx jubatus) died of the disease in November 2004. In the aftermath of this event, banked serum samples collected from 23 wild-caught cheetahs were examined, by the inhibition enzyme-linked immunoassay (ELISA), for antibodies to the protective antigen (PA) of Bacillus anthracis. Of the 23 cheetahs, 16 regularly accessed the reserve. Antibodies to PA were detected in one cheetah collected in May 2004, indicating the disease was occurring well before it was first noticed. This appears to be the first demonstration of naturally acquired anthrax antibodies in cheetahs. The finding of one antibody-positive animal amongst at least 16 potentially exposed individuals is consistent with existing reports that it is uncommon for cheetahs to develop natural immunity to anthrax.

  18. Patient and family physician preferences for care and communication in the eventuality of anthrax terrorism.

    Science.gov (United States)

    Kahan, Ernesto; Fogelman, Yacov; Kitai, Eliezer; Vinker, Shlomo

    2003-08-01

    The threat of bioterrorism consequent to the September 11, 2001 attack in the USA generated suggestions for improved medical response mainly through hospital preparedness. The aim of the present study was to investigate the impact of this period of tension on patients' first choice for care and for receiving relevant information, and on primary care doctors' feelings of responsibility in the eventuality of an anthrax attack. During October 11-31, 2001, 500 patients from 30 clinics throughout Israel were asked to complete a questionnaire on their awareness of the anthrax threat, measures taken to prepare for it, and preferred sources of care and information. Their 30 physicians, and an additional 20, completed a questionnaire on knowledge about anthrax and anthrax-related patient behaviours and clinic visits. The outstanding finding was the low rate (30%) of patients who chose the hospital emergency department as their first choice for care or information if they were worried about an anthrax attack or the media communicated that an attack was in progress. The other two-thirds preferred their family doctor or the health authorities. Most of the physicians (89%) felt it was their responsibility to treat anthrax-infected patients and that they should therefore be supplied with appropriate guidelines. This study suggests that in Israel, a country with a high degree of awareness of civil defence aspects, both patients and primary care doctors believe that family physicians should have a major role in the case of bioterrorist attacks. This must be seriously considered during formulation of relevant health services programmes.

  19. Green revolution vaccines, edible vaccines

    African Journals Online (AJOL)

    Admin

    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. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...

  20. Vaccine Safety

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  1. Vaccines.gov

    Science.gov (United States)

    ... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...

  2. 76 FR 34994 - Vaccine To Protect Children From Anthrax-Public Engagement Workshop

    Science.gov (United States)

    2011-06-15

    .... ADDRESSES: Washington Plaza Hotel, 10 Thomas Circle Northwest, Washington, DC. The call-in details will be.../PREPAREDNESS/LEGAL/BOARDS/NBSB/Pages/default.aspx . FOR FURTHER INFORMATION CONTACT: E-mail: [email protected]/PREPAREDNESS/LEGAL/BOARDS/NBSB/Pages/default.aspx . Procedures for Providing Public Input: Any member of the...

  3. Oral Vaccination Against Anthrax Using a Transgenic Plant Expressing Protective Antigen.

    Science.gov (United States)

    1996-09-01

    Nicotiana plumbaginifolia )" Science 223:496-498. 15. Jefferson, R.A. (1987), "Assaying chimeric genes in plants: The GUS gene fusion system" Plant Mol.Biol...interest. Tobacco ( Nicotiana tabacum cv BY-2) cells were grown in Murashige and Skoog (MS; 1962) media containing 0.2 [tg/ml 2,4-D with shaking at 8

  4. Overcoming Resistance to Change: An Analysis to the Department of Defense's Anthrax Vaccine Immunization Program

    National Research Council Canada - National Science Library

    Johnson, Irene

    2004-01-01

    The goal of this research was to investigate the impact of change on organizations, in the absence of a preparedness program and to develop strategies for overcoming resistance to change, in the midst...

  5. Anthrax Vaccine as a Component of the Strategic National Stockpile: A Dilemma for Homeland Security

    Science.gov (United States)

    2009-12-01

    sociopathic deviations, and instead permits a focusing on the institutional and situational contexts. To accomplish this objective for the social...480–82). 145 Over time, the DHS should choose the right course, steering clear of adopting potential sociopathic pathologies and biases in order to

  6. Defining Moments in MMWR History: CDC’s Response to Intentional Release of Anthrax - 2001

    Centers for Disease Control (CDC) Podcasts

    2017-10-12

    On October 4, 2001, shortly after the September 11 attacks in New York City and Washington, DC, the Palm Beach County Health Department, the Florida State Department of Health, and CDC reported a case of anthrax in a 63-year-old man from Florida. This case was first reported in MMWR and marked the beginning of a series of anthrax cases that resulted from intentional delivery of Bacillus anthracis spores sent through the mail. In this podcast, Dr. Sherif Zaki recalls CDC’s investigation and response to the anthrax attacks.  Created: 10/12/2017 by MMWR.   Date Released: 10/12/2017.

  7. Evaluation of clinical and serological findings for diagnosis of cutaneous anthrax infection after an outbreak.

    Science.gov (United States)

    Gulseren, Duygu; Süzük-Yıldız, Serap; Çelebi, Bekir; Kılıç, Selçuk

    2017-09-01

    Anthrax, caused by the bacterium Bacillus anthracis, is one of the oldest documented infectious diseases in both livestock and humans. We aimed to evaluate clinical findings and risk factors of patients with cutaneous anthrax infection and report anti-lethal factor (LF) IgG and anti-protective antigen (PA) IgG titers in the serologic diagnosis of disease. In this study, serum samples of 18 cutaneous anthrax patients were collected and anti-LF IgG and anti-PA IgG titers were measured by enzyme-linked immunosorbent assay (ELISA). Twelve (67%) males and 6 (33%) females, with a mean age of 36.06 ± 16.58 years were included in the study. Risk factors identified in the patient population studied were slaughtering (28%), flaying (56%), chopping meat (67%), burying diseased animal corpses (17%) and milking (6%) livestock. Black eschar formation (94%), pruritus (78%) and painful lymphadenopathy (61%) were first three common clinical signs and symptoms, respectively. Fourteen (78%) patients produced a positive IgG response against PA, 11 (61%) patients produced against LF. Three (17%) patients had no response to either antigen. A detailed history of contact with sick animals or animal products along with clinical findings should be taken at the first step for the diagnosis of cutaneous anthrax infection. Serologic detection of anti-LF IgG and anti-PA IgG with ELISA may be useful auxillary method for establishing the diagnosis.

  8. Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo

    Science.gov (United States)

    Scobie, Heather M; Wigelsworth, Darran J; Marlett, John M; Thomas, Diane; Rainey, G. Jonah A; Lacy, D. Borden; Manchester, Marianne; Collier, R. John; Young, John A. T

    2006-01-01

    Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis. PMID:17054395

  9. Anthrax in America: A Chronology and Analysis of the Fall 2001 Attacks

    Science.gov (United States)

    2002-11-01

    Glenville, CT, 55 miles west of Oxford. • Officials confirm that the anthrax spores in a letter received by Santiago, Chile pediatrician Antonio Barfi were...process of opening the Leahy letter after two weeks of planning and rehearsals. In charge is John Ezzell , a man described by the Weekend Australian as

  10. Rotavirus vaccines

    Directory of Open Access Journals (Sweden)

    Kang G

    2006-01-01

    Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

  11. The green vaccine: A global strategy to combat infectious and autoimmune diseases

    Science.gov (United States)

    Davoodi-Semiromi, Abdoreza; Samson, Nalapalli; Daniell, Henry

    2009-01-01

    Plant derived oral green vaccines eliminate expenses associated with fermenters, purification, cold storage/transportation and sterile delivery. Green vaccines are expressed via the plant nuclear or chloroplast genomes. Chloroplast expression has advantages of hyper-expression of therapeutic proteins (10,000 copies of trans-gene per cell), efficient oral delivery and transgene containment via maternal inheritance. To date, 23 vaccine antigens against 16 different bacterial, viral or protozoan pathogens have been expressed in chloroplasts. Mice subcutaneously immunized with the chloroplast derived anthrax protective antigen conferred 100% protection against lethal doses of the anthrax toxin. Oral immunization (ORV) of F1-V antigens without adjuvant conferred greater protection (88%) against 50-fold lethal dose of aerosolized plague (Yersinia pestis) than subcutaneous (SQV) immunization (33%). Oral immunization of malarial vaccine antigens fused to the cholera antigen (CTB-AMA1/CTB-Msp1) conferred prolonged immunity (50% life span), 100% protection against cholera toxin challenge and inhibited proliferation of the malarial parasite. Protection was correlated with antigen-specific titers of intestinal, serum IgA & IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. High level expression in edible plant chloroplasts ideal for oral delivery and long-term immunity observed should facilitate development of low cost human vaccines for large populations, at times of outbreak. PMID:19430198

  12. Hepatitis Vaccines

    OpenAIRE

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  13. Rotavirus vaccines

    Science.gov (United States)

    Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

    2014-01-01

    Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

  14. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  15. A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals.

    Science.gov (United States)

    Herrera, Bobby Brooke; Hamel, Donald J; Oshun, Philip; Akinsola, Rolake; Akanmu, Alani S; Chang, Charlotte A; Eromon, Philomena; Folarin, Onikepe; Adeyemi, Kayode T; Happi, Christian T; Lu, Yichen; Ogunsola, Folasade; Kanki, Phyllis J

    2018-05-01

    Ebola virus (EBOV) caused more than 11,000 deaths during the 2013-2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses. Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors. Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.

  16. Frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system.

    Science.gov (United States)

    Cizauskas, Carrie A; Bellan, Steven E; Turner, Wendy C; Vance, Russell E; Getz, Wayne M

    2014-09-01

    Few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. In addition, though most ecological immunology studies employ serological antibody assays, endpoint titre determination is usually based on subjective criteria and needs to be made more objective. Despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found world-wide, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis. Working in the natural anthrax system of Etosha National Park, Namibia, we collected 154 serum samples from plains zebra (Equus quagga), 21 from springbok (Antidorcas marsupialis) and 45 from African elephants (Loxodonta africana) over 2-3 years, resampling individuals when possible for seasonal and longitudinal comparisons. We used enzyme-linked immunosorbent assays to measure anti-anthrax antibody titres and developed three increasingly conservative models to determine endpoint titres with more rigourous, objective mensuration. Between 52 and 87% of zebra, 0-15% of springbok and 3-52% of elephants had measurable anti-anthrax antibody titres, depending on the model used. While the ability of elephants and springbok to mount anti-anthrax adaptive immune responses is still equivocal, our results indicate that zebra in ENP often survive sublethal anthrax infections, encounter most B. anthracis in the wet season and can partially booster their immunity to B. anthracis. Thus, rather than being solely a lethal disease, anthrax often occurs as a sublethal infection in some susceptible hosts. Though we found that adaptive immunity to anthrax wanes rapidly, subsequent and frequent sublethal B. anthracis infections cause maturation of anti-anthrax immunity. By triggering host immune responses, these common sublethal infections may act as

  17. DHEC: Vaccinations

    Science.gov (United States)

    Data, Maps - SC Public Health Diseases and Conditions Flu Tuberculosis STD/HIV and Viral Hepatitis Zika Illnesses E. coli Listeriosis Salmonella Hepatitis A Shellfish Monitoring and Regulation Certified Shippers Vaccines Teen and Preteen Vaccines Vaccines Needed for School Admission Related Topics Perinatal Hepatitis

  18. Highly predictive support vector machine (SVM) models for anthrax toxin lethal factor (LF) inhibitors.

    Science.gov (United States)

    Zhang, Xia; Amin, Elizabeth Ambrose

    2016-01-01

    Anthrax is a highly lethal, acute infectious disease caused by the rod-shaped, Gram-positive bacterium Bacillus anthracis. The anthrax toxin lethal factor (LF), a zinc metalloprotease secreted by the bacilli, plays a key role in anthrax pathogenesis and is chiefly responsible for anthrax-related toxemia and host death, partly via inactivation of mitogen-activated protein kinase kinase (MAPKK) enzymes and consequent disruption of key cellular signaling pathways. Antibiotics such as fluoroquinolones are capable of clearing the bacilli but have no effect on LF-mediated toxemia; LF itself therefore remains the preferred target for toxin inactivation. However, currently no LF inhibitor is available on the market as a therapeutic, partly due to the insufficiency of existing LF inhibitor scaffolds in terms of efficacy, selectivity, and toxicity. In the current work, we present novel support vector machine (SVM) models with high prediction accuracy that are designed to rapidly identify potential novel, structurally diverse LF inhibitor chemical matter from compound libraries. These SVM models were trained and validated using 508 compounds with published LF biological activity data and 847 inactive compounds deposited in the Pub Chem BioAssay database. One model, M1, demonstrated particularly favorable selectivity toward highly active compounds by correctly predicting 39 (95.12%) out of 41 nanomolar-level LF inhibitors, 46 (93.88%) out of 49 inactives, and 844 (99.65%) out of 847 Pub Chem inactives in external, unbiased test sets. These models are expected to facilitate the prediction of LF inhibitory activity for existing molecules, as well as identification of novel potential LF inhibitors from large datasets. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event Symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lesperance, Ann M.

    2008-06-30

    On March 19, 2008, policy makers, emergency managers, and medical and Public Health officials convened in Seattle, Washington, for a workshop on Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event. The day-long symposium was aimed at generating a dialogue about restoration and recovery through a discussion of the associated challenges that impact entire communities, including people, infrastructure, and critical systems.

  20. Indirect Detection Of Bacillus Anthracis (Anthrax) Using Amplified Gamma Phage-Based Assays

    Science.gov (United States)

    2007-11-01

    enter 26 Figure 3.0 Model of anthrax toxin entry into eukaryotic cells 27 the lungs and into the mucus membrane...extract from porcine and mixture meat and milk peptones, 2.0 g D(+) glucose, 5.0 g NaCl and 2.5 g disodium phosphate) and TSB (g/L: 17.0 pancreatic...are present in blood serum, lymph fluid, gastric secretions, milk , and saliva. Serum antibody concentrations are commonly determined using the

  1. Anthrax outbreak in a Swedish beef cattle herd - 1st case in 27 years: Case report

    Directory of Open Access Journals (Sweden)

    Granberg Malin

    2010-02-01

    Full Text Available Abstract After 27 years with no detected cases, an outbreak of anthrax occurred in a beef cattle herd in the south of Sweden. The outbreak was unusual as it occurred in winter, in animals not exposed to meat-and-bone meal, in a non-endemic country. The affected herd consisted of 90 animals, including calves and young stock. The animals were kept in a barn on deep straw bedding and fed only roughage. Seven animals died during 10 days, with no typical previous clinical signs except fever. The carcasses were reportedly normal in appearance, particularly as regards rigor mortis, bleeding and coagulation of the blood. Subsequently, three more animals died and anthrax was suspected at necropsy and confirmed by culture and PCR on blood samples. The isolated strain was susceptible to tetracycline, ciprofloxacin and ampicillin. Subtyping by MLVA showed the strain to cluster with isolates in the A lineage of Bacillus anthracis. Environmental samples from the holding were all negative except for two soil samples taken from a spot where infected carcasses had been kept until they were picked up for transport. The most likely source of the infection was concluded to be contaminated roughage, although this could not be substantiated by laboratory analysis. The suspected feed was mixed with soil and dust and originated from fields where flooding occurred the previous year, followed by a dry summer with a very low water level in the river allowing for the harvesting on soil usually not exposed. In the early 1900s, animal carcasses are said to have been dumped in this river during anthrax outbreaks and it is most likely that some anthrax spores could remain in the area. The case indicates that untypical cases in non-endemic areas may be missed to a larger extent than previously thought. Field tests allowing a preliminary risk assessment of animal carcasses would be helpful for increased sensitivity of detection and prevention of further exposure to the causative

  2. False alarms, real challenges--one university's communication response to the 2001 anthrax crisis.

    Science.gov (United States)

    Clarke, Christopher E; Chess, Caron

    2006-01-01

    Considerable research exists on how government agencies at the federal, state, and local levels communicated during the fall 2001 anthrax attacks. However, there is little research on how other institutions handled this crisis, in terms of their response to potential anthrax contamination (aka "white powder scares") and their approach to disseminating important health and safety information. In this article, we investigate a major university's communication response to the anthrax crisis. First, we describe its communication experiences relating to a large white powder scare that occurred in October 2001. Second, we describe the university's broader communication efforts in terms of several important elements of risk communication research, including influence of source attributes, key messages, preferred channels, responses to information requests, and organizational influences. This study underlines that an institution does not have to be directly affected by a crisis to find itself on the communication "front lines." Moreover, other institutions may find it useful to learn from the experiences of this university, so that they may communicate more effectively during future crises.

  3. Confirmation of acute nitrate poisoning differentiating from anthrax in three Indian indigenous cattle

    Directory of Open Access Journals (Sweden)

    Kumaresan Nagarajan

    2015-03-01

    Full Text Available This article reports cases of nitrate poisoning in Indian indigenous cattle breeds comprising two Gir cows aging 4 years each, and one Barugur cow at 1.5 years of age. The cattle with case history of sudden death and oozing of partially clotted blood from the anal opening were brought to the Central University Laboratory (CUL, Center for Animal Health Studies (CAHS, Tamil Nadu Veterinary and Animal Sciences University (TANUVAS for diagnostic investigation with a suspicion of anthrax. According to anamnesis, all the animals were clinically normal and did not reveal any abnormality on the previous day. The animals were fed with recently harvested sorghum leaves and stalks. Smears examined for anthrax were found negative. Biological test (mice inoculation for anthrax was also negative. Gross lesions on necropsy examination of the carcases were suggestive of nitrate intoxication. Finally, nitrate intoxication of these cattle was confirmed by chemical and toxicological analysis of fodder, rumen content, aqueous humor, liver, kidney and urine.

  4. Anthrax and the Geochemistry of Soils in the Contiguous United States

    Directory of Open Access Journals (Sweden)

    Dale W. Griffin

    2014-08-01

    Full Text Available Soil geochemical data from sample sites in counties that reported occurrences of anthrax in wildlife and livestock since 2000 were evaluated against counties within the same states (MN, MT, ND, NV, OR, SD and TX that did not report occurrences. These data identified the elements, calcium (Ca, manganese (Mn, phosphorus (P and strontium (Sr, as having statistically significant differences in concentrations between county type (anthrax occurrence versus no occurrence. Tentative threshold values of the lowest concentrations of each of these elements (Ca = 0.43 wt %, Mn = 142 mg/kg, P = 180 mg/kg and Sr = 51 mg/kg and average concentrations (Ca = 1.3 wt %, Mn = 463 mg/kg, P = 580 mg/kg and Sr = 170 mg/kg were identified from anthrax-positive counties as prospective investigative tools in determining whether an outbreak had “potential” or was “likely” at any given geographic location in the contiguous United States.

  5. Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

    Science.gov (United States)

    Cote, Christopher; Welkos, Susan; Manchester, Marianne; Young, John A. T.

    2012-01-01

    Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream. PMID:22511955

  6. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

    Directory of Open Access Journals (Sweden)

    Jane P. F. Bai

    2017-03-01

    Full Text Available Developing drugs to treat the toxic effects of lethal toxin (LT and edema toxin (ET produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.

  7. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  8. Gastrointestinal helminths may affect host susceptibility to anthrax through seasonal immune trade-offs.

    Science.gov (United States)

    Cizauskas, Carrie A; Turner, Wendy C; Wagner, Bettina; Küsters, Martina; Vance, Russell E; Getz, Wayne M

    2014-11-12

    Most vertebrates experience coinfections, and many pathogen-pathogen interactions occur indirectly through the host immune system. These interactions are particularly strong in mixed micro-macroparasite infections because of immunomodulatory effects of helminth parasites. While these trade-offs have been examined extensively in laboratory animals, few studies have examined them in natural systems. Additionally, many wildlife pathogens fluctuate seasonally, at least partly due to seasonal host immune changes. We therefore examined seasonality of immune resource allocation, pathogen abundance and exposure, and interactions between infections and immunity in plains zebra (Equus quagga) in Etosha National Park (ENP), Namibia, a system with strongly seasonal patterns of gastrointestinal (GI) helminth infection intensity and concurrent anthrax outbreaks. Both pathogens are environmentally transmitted, and helminth seasonality is driven by environmental pressures on free living life stages. The reasons behind anthrax seasonality are currently not understood, though anthrax is less likely directly driven by environmental factors. We measured a complex, interacting set of variables and found evidence that GI helminth infection intensities, eosinophil counts, IgE and IgGb antibody titers, and possibly IL-4 cytokine signaling were increased in wetter seasons, and that ectoparasite infestations and possibly IFN-γ cytokine signaling were increased in drier seasons. Monocyte counts and anti-anthrax antibody titers were negatively associated with wet season eosinophilia, and monocytes were negatively correlated with IgGb and IgE titers. Taken together, this supports the hypothesis that ENP wet seasons are characterized by immune resource allocation toward Th-2 type responses, while Th1-type immunity may prevail in drier seasons, and that hosts may experience Th1-Th2 trade-offs. We found evidence that this Th2-type resource allocation is likely driven by GI parasite infections

  9. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

    Science.gov (United States)

    Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

  10. Crystallization and preliminary X-ray analysis of the vWA domain of human anthrax toxin receptor 1

    International Nuclear Information System (INIS)

    Cai, Chenguang; Zhao, Ying; Tong, Xiaohang; Fu, Sheng; Li, Yuanyuan; Wu, Yang; Li, Xumei; Lou, Zhiyong

    2010-01-01

    The vWA domain of human anthrax toxin receptor 1 was overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 1.8 Å resolution. The Gram-positive spore-forming bacterium Bacillus anthracis causes anthrax by secreting anthrax toxin, which consists of protective antigen (PA), lethal factor and oedema factor. Binding of PA to receptors triggers the multi-step process of anthrax toxin entry into target cells. Two distinct cellular receptors, ANTXR1 (also known as tumour endothelial marker 8; TEM8) and ANTXR2 (also known as capillary morphogenesis protein 2; CMG2), for anthrax toxin have been identified. Although the crystal structure of the extracellular von Willebrand factor A (vWA) domain of CMG2 has been reported, the difference between the vWA domains of TEM8 and CMG2 remains unclear because there are no structural data for the TEM8 vWA domain. In this report, the TEM8 vWA domain was expressed, purified and crystallized. X-ray diffraction data were collected to 1.8 Å resolution from a single crystal, which belonged to space group P1 with unit-cell parameters a = 65.9, b = 66.1, c = 74.4 Å, α = 63.7, β = 88.2, γ = 59.9°

  11. Hepatitis Vaccines

    Directory of Open Access Journals (Sweden)

    Sina Ogholikhan

    2016-03-01

    Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.

  12. Hepatitis Vaccines

    Science.gov (United States)

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  13. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  14. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  15. FLU VACCINATION

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  16. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  17. Approval of raxibacumab for the treatment of inhalation anthrax under the US Food and Drug Administration Animal rule

    Directory of Open Access Journals (Sweden)

    Chia-Wei eTsai

    2015-12-01

    Full Text Available On December 14, 2012, the FDA approved raxibacumab, the first product developed under Project BioShield to achieve this milestone, and the first biologic product to be approved through the FDA animal efficacy rule (or Animal Rule. Raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. The approval of Raxibacumab illustrates many of the challenges that product developers may encounter when pursuing approval under the Animal Rule and highlights a number of important regulatory and policy issues.

  18. Estimating the location and spatial extent of a covert anthrax release.

    Directory of Open Access Journals (Sweden)

    Judith Legrand

    2009-01-01

    Full Text Available Rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. Previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. We extend the scope of these methods by proposing a method for characterizing the time, strength, and also the location of an aerosolized pathogen release. A back-calculation method is developed allowing the characterization of the release based on the data on the first few observed cases of the subsequent outbreak, meteorological data, population densities, and data on population travel patterns. We evaluate this method on small simulated anthrax outbreaks (about 25-35 cases and show that it could date and localize a release after a few cases have been observed, although misspecifications of the spore dispersion model, or the within-host dynamics model, on which the method relies can bias the estimates. Our method could also provide an estimate of the outbreak's geographical extent and, as a consequence, could help to identify populations at risk and, therefore, requiring prophylactic treatment. Our analysis demonstrates that while estimates based on the first ten or 15 observed cases were more accurate and less sensitive to model misspecifications than those based on five cases, overall mortality is minimized by targeting prophylactic treatment early on the basis of estimates made using data on the first five cases. The method we propose could provide early estimates of the time, strength, and location of an aerosolized anthrax release and the geographical extent of the subsequent outbreak. In addition, estimates of release features could be used to parameterize more detailed models allowing the simulation of control strategies and intervention logistics.

  19. DNA Vaccines

    Indian Academy of Sciences (India)

    diseases. Keywords. DNA vaccine, immune response, antibodies, infectious diseases. GENERAL .... tein vaccines require expensive virus/protein purification tech- niques as ... sphere continue to remain major health hazards in developing nations. ... significance since it can be produced at a very low cost and can be stored ...

  20. Vaccination Policies

    NARCIS (Netherlands)

    Verweij, M.F.

    2013-01-01

    Vaccination involves priming the immune system with an antigenic agent that mimics a virus or bacterium, which results in immunity against the “real” microorganism. Collective vaccination policies have played an important role in the control of infectious disease worldwide. They can serve the

  1. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  2. Rotavirus Vaccine

    Science.gov (United States)

    Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...

  3. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor

    Energy Technology Data Exchange (ETDEWEB)

    Maize, Kimberly M.; Kurbanov, Elbek K.; Johnson, Rodney L.; Amin, Elizabeth Ambrose; Finzel, Barry C. (UMM)

    2016-07-05

    The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1'* which might afford new opportunities to design selective inhibitors that target this subsite.

  4. Anthrax toxin: the long and winding road that leads to the kill.

    Science.gov (United States)

    Abrami, Laurence; Reig, Nuria; van der Goot, F Gisou

    2005-02-01

    The past five years have led to a tremendous increase in our molecular understanding of the mode of action of the anthrax toxin, one of the two main virulence factors produced by Bacillus anthracis. The structures of each of the three components of the toxin--lethal factor (LF), edema factor (EF) and protective antigen (PA)--have been solved not only in their monomeric forms but, depending on the subunit, in a heptameric form, bound to their substrate, co-factor or receptor. The endocytic route followed by the toxin has also been unraveled and the enzymatic mechanisms of EF and LF elucidated.

  5. [Genodiagnosis and molecular typing of the pathogens for plague, cholera, and anthrax].

    Science.gov (United States)

    Kutyrev, V V; Smirnova, N I

    2003-01-01

    The paper contains a survey of published data about the use of DNA-diagnostics in indicating and identifying the causative agents of highly dangerous infections like plague, cholera and anthrax. A discussion of data about the genetic relationship between strains of the mentioned causative agents isolated from different sources by using the molecular-typing methods as well as about the evolution ties between strains of different origins is in the focus of attention. Results of comparative studies of nucleotide sequences of genomes or of individual genomes in different Yersinia pestis, Vibrio cholerae and Bacillus anthracis strains, which are indicative of the evolution of their pathogenicity, are also under discussion.

  6. [Tobacco--a highly efficient producer of vaccines].

    Science.gov (United States)

    Budzianowski, Jaromir

    2010-01-01

    Along with the depreciation of tobacco as a source of nicotine-containing commercial products, the increase of its appreciation as a potential producer of recombinant therapeutical proteins can be observed. Two species of tobacco--Nicotiana tabacum L. and N. benthamiana are easily grown by well established methods of field or green-house cultivation or cell culture, yield high biomass and soluble protein content, can be easily transformed by several methods and are not food for humans or feed for animals. Expression of foreign proteins, including vaccines, can be achieved in those plants either through stable transformation of nuclear or plastid (chloroplast) genomes or by transient transformation using infection with plant virus or bacteria--Agrobacterium tumefaciens (agroinfiltration). The most advanced mode of agrofiltration termed magnifection, which combines benefits of virus and Agrobacterium and depends on using Agrobacterium with viral pro-vectors, enables high-yield and rapid expression of therapeutical proteins, even in a few days, and can be employed on an industrial scale. Expression of many antigenic proteins, which may serve as antiviral, antibacterial, antiprotozoan and anticancer vaccines, and additionally a few autoantigens designed for the treatment of autoimunogenic diseases, like diabetes, have been achieved in tobacco. To date, a vaccine against Newcastle virus disease in poultry produced by tobacco cell culture has been approved for commercial application and several other vaccines are in advanced stage of development. The possibility of a high-level production of vaccines in tobacco against pandemic influenza or anthrax and plague due to a bioterroristic attack, as well as of individualised anticancer vaccines against non-Hodgkin's lymphoma (NHL) in a much shorter period of time than by traditional methods became realistic and hence caused increased interest in tobacco as a high-efficient producer of vaccines not only of specialistic

  7. Whither vaccines?

    Science.gov (United States)

    Rodrigues, Charlene M C; Pinto, Marta V; Sadarangani, Manish; Plotkin, Stanley A

    2017-06-01

    Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  8. Role of visible light-activated photocatalyst on the reduction of anthrax spore-induced mortality in mice.

    Directory of Open Access Journals (Sweden)

    Jyh-Hwa Kau

    Full Text Available BACKGROUND: Photocatalysis of titanium dioxide (TiO(2 substrates is primarily induced by ultraviolet light irradiation. Anion-doped TiO(2 substrates were shown to exhibit photocatalytic activities under visible-light illumination, relative environmentally-friendly materials. Their anti-spore activity against Bacillus anthracis, however, remains to be investigated. We evaluated these visible-light activated photocatalysts on the reduction of anthrax spore-induced pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Standard plating method was used to determine the inactivation of anthrax spore by visible light-induced photocatalysis. Mouse models were further employed to investigate the suppressive effects of the photocatalysis on anthrax toxin- and spore-mediated mortality. We found that anti-spore activities of visible light illuminated nitrogen- or carbon-doped titania thin films significantly reduced viability of anthrax spores. Even though the spore-killing efficiency is only approximately 25%, our data indicate that spores from photocatalyzed groups but not untreated groups have a less survival rate after macrophage clearance. In addition, the photocatalysis could directly inactivate lethal toxin, the major virulence factor of B. anthracis. In agreement with these results, we found that the photocatalyzed spores have tenfold less potency to induce mortality in mice. These data suggest that the photocatalysis might injury the spores through inactivating spore components. CONCLUSION/SIGNIFICANCE: Photocatalysis induced injuries of the spores might be more important than direct killing of spores to reduce pathogenicity in the host.

  9. Patients' request for and emergency physicians' prescription of antimicrobial prophylaxis for anthrax during the 2001 bioterrorism-related outbreak

    Directory of Open Access Journals (Sweden)

    Aber Robert C

    2005-01-01

    Full Text Available Abstract Background Inappropriate use of antibiotics by individuals worried about biological agent exposures during bioterrorism events is an important public health concern. However, little is documented about the extent to which individuals with self-identified risk of anthrax exposure approached physicians for antimicrobial prophylaxis during the 2001 bioterrorism attacks in the United States. Methods We conducted a telephone survey of randomly selected members of the Pennsylvania Chapter of the American College of Emergency Physicians to assess patients' request for and emergency physicians' prescription of antimicrobial agents during the 2001 anthrax attacks. Results Ninety-seven physicians completed the survey. Sixty-four (66% respondents had received requests from patients for anthrax prophylaxis; 16 (25% of these physicians prescribed antibiotics to a total of 23 patients. Ten physicians prescribed ciprofloxacin while 8 physicians prescribed doxycycline. Conclusion During the 2001 bioterrorist attacks, the majority of the emergency physicians we surveyed encountered patients who requested anthrax prophylaxis. Public fears may lead to a high demand for antibiotic prophylaxis during bioterrorism events. Elucidation of the relationship between public health response to outbreaks and outcomes would yield insights to ease burden on frontline clinicians and guide strategies to control inappropriate antibiotic allocation during bioterrorist events.

  10. 9 CFR 310.9 - Anthrax; carcasses not to be eviscerated; disposition of affected carcasses; hides, hoofs, horns...

    Science.gov (United States)

    2010-01-01

    ... have handled anthrax material is thorough cleansing of the hands and arms with liquid soap and running... Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND... request to the Scientific Services, Meat and Poultry Inspection, Food Safety and Inspection Service, U.S...

  11. 9 CFR 309.7 - Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways.

    Science.gov (United States)

    2010-01-01

    ...; cleaning and disinfection of infected livestock pens and driveways. 309.7 Section 309.7 Animals and Animal... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and... followed immediately by a thorough disinfection of the exposed premises by soaking the ground, fences...

  12. Anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria.

    Directory of Open Access Journals (Sweden)

    Chen Sun

    Full Text Available A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs. Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis.

  13. Detection of anthrax lef with DNA-based photonic crystal sensors

    Science.gov (United States)

    Zhang, Bailin; Dallo, Shatha; Peterson, Ralph; Hussain, Syed; Weitao, Tao; Ye, Jing Yong

    2011-12-01

    Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

  14. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Jurriaan Huskens

    2011-10-01

    Full Text Available A supramolecular platform based on self-assembled monolayers (SAMs has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. A Eu(III-EDTA complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. The self-assembly of the Eu(III-EDTA conjugate and naphthalene β-diketone as an antenna resulted in the formation of a highly luminescent lanthanide complex on the microchannel surface. Detection of different phosphate anions and aromatic carboxylic acids was demonstrated by monitoring the decrease in red emission following displacement of the antenna by the analyte. Among these analytes, adenosine triphosphate (ATP and pyrophosphate, as well as dipicolinic acid (DPA which is a biomarker for anthrax, showed a strong response. Parallel fabrication of five sensing SAMs in a single multichannel chip was performed, as a first demonstration of phosphate and carboxylic acid screening in a multiplexed format that allows a general detection platform for both analyte systems in a single test run with µM and nM detection sensitivity for ATP and DPA, respectively.

  15. Functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin pore.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    2009-07-01

    Full Text Available A key step of anthrax toxin action involves the formation of a protein-translocating pore within the endosomal membrane by the Protective Antigen (PA moiety. Formation of this transmembrane pore by PA involves interaction of the seven 2beta2-2beta3 loops of the heptameric precursor to generate a 14-strand transmembrane beta barrel.We examined the effects on pore formation, protein translocation, and cytotoxicity, of mutating two phenylalanines, F313 and F314, that lie at the tip the beta barrel, and a third one, F324, that lies part way up the barrel.Our results show that the function of these phenylalanine residues is to mediate membrane insertion and formation of stable transmembrane channels. Unlike F427, a key luminal residue in the cap of the pore, F313, F314, and F324 do not directly affect protein translocation through the pore. Our findings add to our knowledge of structure-function relationships of a key virulence factor of the anthrax bacillus.

  16. Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent F. tularensis subsp. tularensis

    Science.gov (United States)

    Jia, Qingmei; Horwitz, Marcus A.

    2018-01-01

    Francisella tularensis is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed “Foshay” vaccine, subunit vaccines comprising F. tularensis protein(s) or lipoproteins(s) in an adjuvant formulation, and the F. tularensis Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals—especially mice—but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies. The U.S.A. 2001 anthrax bioterrorism attack spawned renewed interest in vaccines against potential biowarfare agents including F. tularensis. Since live attenuated—but not killed or subunit—vaccines have shown promising efficacy and since vaccine efficacy against respiratory challenge with less virulent subspecies holarctica or F. novicida, or against non-respiratory challenge with virulent subsp. tularensis (Type A) does not reliably predict vaccine efficacy against respiratory challenge with virulent subsp. tularensis, the route of transmission and species of greatest concern in a bioterrorist attack, in this review, we focus on live attenuated tularemia vaccine candidates tested against respiratory challenge with virulent Type A strains, including homologous vaccines derived from mutants of subsp. holarctica, F. novicida, and subsp. tularensis, and heterologous vaccines developed using viral or bacterial vectors to express F. tularensis immunoprotective antigens. We compare the virulence and efficacy of these vaccine candidates with that of LVS and discuss factors that can significantly impact the development and evaluation of live attenuated tularemia vaccines. Several vaccines meet what we would consider the minimum criteria for vaccines to go forward into clinical development—safety greater than LVS and efficacy at least as great as LVS, and of these, several meet the

  17. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    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....

  18. Flu Vaccine Safety Information

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) ... safety of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. ...

  19. Thimerosal in Flu Vaccine

    Science.gov (United States)

    ... Seasonal Avian Swine Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend ... and/or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose ...

  20. Ear Infection and Vaccines

    Science.gov (United States)

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

  1. Antipneumococcal vaccination

    Directory of Open Access Journals (Sweden)

    Gian Vincenzo Zuccotti

    2013-06-01

    Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  2. Role of Food Insecurity in Outbreak of Anthrax Infections among Humans and Hippopotamuses Living in a Game Reserve Area, Rural Zambia.

    Science.gov (United States)

    Lehman, Mark W; Craig, Allen S; Malama, Constantine; Kapina-Kany'anga, Muzala; Malenga, Philip; Munsaka, Fanny; Muwowo, Sergio; Shadomy, Sean; Marx, Melissa A

    2017-09-01

    In September 2011, a total of 511 human cases of anthrax (Bacillus anthracis) infection and 5 deaths were reported in a game management area in the district of Chama, Zambia, near where 85 hippopotamuses (Hippopotamus amphibious) had recently died of suspected anthrax. The human infections generally responded to antibiotics. To clarify transmission, we conducted a cross-sectional, interviewer-administered household survey in villages where human anthrax cases and hippopotamuses deaths were reported. Among 284 respondents, 84% ate hippopotamus meat before the outbreak. Eating, carrying, and preparing meat were associated with anthrax infection. Despite the risk, 23% of respondents reported they would eat meat from hippopotamuses found dead again because of food shortage (73%), lack of meat (12%), hunger (7%), and protein shortage (5%). Chronic food insecurity can lead to consumption of unsafe foods, leaving communities susceptible to zoonotic infection. Interagency cooperation is necessary to prevent outbreaks by addressing the root cause of exposure, such as food insecurity.

  3. Passive vaccination with a human monoclonal antibody: generation of antibodies and studies for efficacy in Bacillus anthracis infections.

    Science.gov (United States)

    vor dem Esche, Ulrich; Huber, Maria; Zgaga-Griesz, Andrea; Grunow, Roland; Beyer, Wolfgang; Hahn, Ulrike; Bessler, Wolfgang G

    2011-07-01

    A major difficulty in creating human monoclonal antibodies is the lack of a suitable myeloma cell line to be used for fusion experiments. In order to create fully human monoclonal antibodies for passive immunization, the human mouse heteromyeloma cell line CB-F7 was evaluated. Using this cell line, we generated human monoclonal antibodies against Bacillus anthracis toxin components. Antibodies against protective antigen (PA) and against lethal factor (LF) were obtained using peripheral blood lymphocytes (PBLs) from persons vaccinated with the UK anthrax vaccine. PBL were fused with the cell line CB-F7. We obtained several clones producing PA specific Ig and one clone (hLF1-SAN) producing a monoclonal antibody (hLF1) directed against LF. The LF binding antibody was able to neutralize Anthrax toxin activity in an in vitro neutralization assay, and preliminary in vivo studies in mice also indicated a trend towards protection. We mapped the epitope of the antibody binding to LF by dot blot analysis and ELIFA using 80 synthetic LF peptides of 20 amino acid lengths with an overlapping range of 10 amino acids. Our results suggest the binding of the monoclonal antibody to the peptide regions 121-150 or 451-470 of LF. The Fab-fragment of the antibody hLF1 was cloned in Escherichia coli and could be useful as part of a fully human monoclonal antibody for the treatment of Anthrax infections. In general, our studies show the applicability of the CB-F7 line to create fully human monoclonal antibodies for vaccination. Copyright © 2010 Elsevier GmbH. All rights reserved.

  4. PREDICTION OF AEROSOL HAZARDS ARISING FROM THE OPENING OF AN ANTHRAX-TAINTED LETTER IN AN OPEN OFFICE ENVIRONMENT USING COMPUTATIONAL FLUID DYNAMICS

    OpenAIRE

    FUE-SANG LIEN; HUA JI; EUGENE YEE; BILL KOURNIKAKIS

    2010-01-01

    Early experimental work, conducted at Defence R&D Canada–Suffield, measured and characterized the personal and environmental contamination associated with simulated anthrax-tainted letters under a number of different scenarios in order to obtain a better understanding of the physical and biological processes for detecting, assessing, and formulating potential mitigation strategies for managing the risks associated with opening an anthrax-tainted letter. These experimental investigations have ...

  5. Production of vaccines for treatment of infectious diseases by transgenic plants

    Directory of Open Access Journals (Sweden)

    Kristina LEDL

    2016-04-01

    Full Text Available Since the first pathogen antigen was expressed in transgenic plants with the aim of producing edible vaccine in early 1990s, transgenic plants have become a well-established expression system for production of alternative vaccines against various human and animal infectious diseases. The main focus of plant expression systems in the last five years has been on improving expression of well-studied antigens such as porcine reproductive and respiratory syndrome (PRRSV, bovine viral diarrhea disease virus (BVDV, footh and mouth disease virus (FMDV, hepatitis B surface antigen (HBsAg, rabies G protein, rotavirus, Newcastle disease virus (NDV, Norwalk virus capsid protein (NVCP, avian influenza virus H5N1, Escherichia coli heat-labile enterotoxin subunit B (LT-B, cholera toxin B (CT-B, human immunodeficiency virus (HIV, artherosclerosis, ebola and anthrax. Significant increases in expression have been obtained using improved expression vectors, different plant species and transformation methods.

  6. Design of monodisperse and well-defined polypeptide-based polyvalent inhibitors of anthrax toxin.

    Science.gov (United States)

    Patke, Sanket; Boggara, Mohan; Maheshwari, Ronak; Srivastava, Sunit K; Arha, Manish; Douaisi, Marc; Martin, Jacob T; Harvey, Ian B; Brier, Matthew; Rosen, Tania; Mogridge, Jeremy; Kane, Ravi S

    2014-07-28

    The design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. The ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure-activity relationships and for designing potent polyvalent molecules. To that end, we designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin-binding peptide were separated by flexible peptide linkers. By tuning the valency and linker length, we designed polyvalent inhibitors that were over four orders of magnitude more potent than the corresponding monovalent ligands. This strategy for the rational design of monodisperse polyvalent molecules may not only be broadly applicable for the inhibition of toxins and pathogens, but also for controlling the nanoscale organization of cellular receptors to regulate signaling and the fate of stem cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Facilitation of risk communication during the anthrax attacks of 2001: the organizational backstory.

    Science.gov (United States)

    Chess, Caron; Clarke, Lee

    2007-09-01

    The anthrax attacks of 2001 created risk communication problems that cannot be fully understood without appreciating the dynamics among organizations. Case studies of communication in New Jersey, consisting of interviews with a range of participants, found that existing organizational and professional networks facilitated trust among decisionmakers. This interpersonal trust improved communication among agencies and thereby risk communication with the public. For example, "white powder scares" were a problem even in places without contamination. Professionals' trust in each other was vital for responding productively. Conversely, organizational challenges, including conflict among agencies, hindered communication with key audiences. Although centralization and increased control are often seen as the remedy for communicative confusion, they also can quash the improvisational responses needed during crises.

  8. Initiating informatics and GIS support for a field investigation of Bioterrorism: The New Jersey anthrax experience

    Directory of Open Access Journals (Sweden)

    Skinner Ric

    2003-11-01

    Full Text Available Abstract Background The investigation of potential exposure to anthrax spores in a Trenton, New Jersey, mail-processing facility required rapid assessment of informatics needs and adaptation of existing informatics tools to new physical and information-processing environments. Because the affected building and its computers were closed down, data to list potentially exposed persons and map building floor plans were unavailable from the primary source. Results Controlling the effects of anthrax contamination required identification and follow-up of potentially exposed persons. Risk of exposure had to be estimated from the geographic relationship between work history and environmental sample sites within the contaminated facility. To assist in establishing geographic relationships, floor plan maps of the postal facility were constructed in ArcView Geographic Information System (GIS software and linked to a database of personnel and visitors using Epi Info and Epi Map 2000. A repository for maintaining the latest versions of various documents was set up using Web page hyperlinks. Conclusions During public health emergencies, such as bioterrorist attacks and disease epidemics, computerized information systems for data management, analysis, and communication may be needed within hours of beginning the investigation. Available sources of data and output requirements of the system may be changed frequently during the course of the investigation. Integrating data from a variety of sources may require entering or importing data from a variety of digital and paper formats. Spatial representation of data is particularly valuable for assessing environmental exposure. Written documents, guidelines, and memos important to the epidemic were frequently revised. In this investigation, a database was operational on the second day and the GIS component during the second week of the investigation.

  9. Green revolution vaccines, edible vaccines | Tripurani | African ...

    African Journals Online (AJOL)

    Edible vaccines are sub-unit vaccines where the selected genes are introduced into the plants and the transgenic plant is then induced to manufacture the encoded protein. Edible vaccines are mucosal-targeted vaccines where stimulation of both systematic and mucosal immune network takes place. Foods under study ...

  10. Overcoming Resistance to Change: An Analysis to the Department of Defense’s Anthrax Vaccine Immunization Program

    Science.gov (United States)

    2004-06-01

    Prahalad , C. K. (1981). Headquarters influence and strategic control in MNCs. Sloan Management Review, 23(1), 15-29. Gagne, M., Koestner, R...p. 124). Rousseau, et al. (1998) defined trust as “a psychological state comprising the intention to accept vulnerability based on the positive...expectations of the intentions or behavior of another” (p. 395). McAllister (1995) defined trust as “the extent to which a person is confident in and

  11. Valuing vaccination.

    Science.gov (United States)

    Bärnighausen, Till; Bloom, David E; Cafiero-Fonseca, Elizabeth T; O'Brien, Jennifer Carroll

    2014-08-26

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.

  12. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

    Science.gov (United States)

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-11-07

    Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

  13. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  14. Role of the Antigen Capture Pathway in the Induction of a Neutralizing Antibody Response to Anthrax Protective Antigen

    Directory of Open Access Journals (Sweden)

    Anita Verma

    2018-02-01

    Full Text Available Toxin neutralizing antibodies represent the major mode of protective immunity against a number of toxin-mediated bacterial diseases, including anthrax; however, the cellular mechanisms that lead to optimal neutralizing antibody responses remain ill defined. Here we show that the cellular binding pathway of anthrax protective antigen (PA, the binding component of anthrax toxin, determines the toxin neutralizing antibody response to this antigen. PA, which binds cellular receptors and efficiently enters antigen-presenting cells by receptor-mediated endocytosis, was found to elicit robust anti-PA IgG and toxin neutralizing antibody responses. In contrast, a receptor binding-deficient mutant of PA, which does not bind receptors and only inefficiently enters antigen-presenting cells by macropinocytosis, elicited very poor antibody responses. A chimeric protein consisting of the receptor binding-deficient PA mutant tethered to the binding subunit of cholera toxin, which efficiently enters cells using the cholera toxin receptor rather than the PA receptor, elicited an anti-PA IgG antibody response similar to that elicited by wild-type PA; however, the chimeric protein elicited a poor toxin neutralizing antibody response. Taken together, our results demonstrate that the antigen capture pathway can dictate the magnitudes of the total IgG and toxin neutralizing antibody responses to PA as well as the ratio of the two responses.

  15. Immunoassay for Capsular Antigen of Bacillus anthracis Enables Rapid Diagnosis in a Rabbit Model of Inhalational Anthrax.

    Directory of Open Access Journals (Sweden)

    Marcellene A Gates-Hollingsworth

    Full Text Available Inhalational anthrax is a serious biothreat. Effective antibiotic treatment of inhalational anthrax requires early diagnosis; the further the disease has progressed, the less the likelihood for cure. Current means for diagnosis such as blood culture require several days to a result and require advanced laboratory infrastructure. An alternative approach to diagnosis is detection of a Bacillus anthracis antigen that is shed into blood and can be detected by rapid immunoassay. The goal of the study was to evaluate detection of poly-γ-D-glutamic acid (PGA, the capsular antigen of B. anthracis, as a biomarker surrogate for blood culture in a rabbit model of inhalational anthrax. The mean time to a positive blood culture was 26 ± 5.7 h (mean ± standard deviation, whereas the mean time to a positive ELISA was 22 ± 4.2 h; P = 0.005 in comparison with blood culture. A lateral flow immunoassay was constructed for detection of PGA in plasma at concentrations of less than 1 ng PGA/ml. Use of the lateral flow immunoassay for detection of PGA in the rabbit model found that antigen was detected somewhat earlier than the earliest time point at which the blood culture became positive. The low cost, ease of use, and rapid time to result of the lateral flow immunoassay format make an immunoassay for PGA a viable surrogate for blood culture for detection of infection in individuals who have a likelihood of exposure to B. anthracis.

  16. Vaccines and Thimerosal

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  17. Vaccine Adverse Events

    Science.gov (United States)

    ... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...

  18. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

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

  19. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  20. Forecasting of interaction between bee propolis and protective antigenic domain in anthrax using the software and bioinformatics web servers

    Directory of Open Access Journals (Sweden)

    Elmira Mohammadi

    2017-01-01

    Full Text Available Background: Protective antigen of anthrax toxin, after touching the cell receptors, plays an important role in the pathogenesis of toxin. The purpose of this study was to investigate the interaction of anthrax toxin protective antigen and four great combination propolis included caffeic acid, benzyl caffeate, cinnamic acid and kaempferol using the softwares and bioinformatics web servers. Methods: Three-dimensional structure of protective antigen (receptor obtains from Protein Data Bank (PDB. Four of the main components from propolis were selected          as ligand and their 3D-structures were obtained from ChemSpider and ZINC     compound database. The interaction of each ligand and receptor was assessed                   by SwissDock server (http://www.swissdock.ch/ and BSP-SLIM server (http://zhanglab.ccmb.med.umich.edu/BSP-SLIM. Docking results appears with Fullfitness numbers (in kcal/mol. Identification of amino acids involved in ligand and receptor interaction, was performed using the Chimera software; UCSF Chimera program (http://www.cgl.ucsf.edu/. Results: The results of interaction between propolis components and protective antigen by BSP-SLIM server showed that the most interaction was related with benzyl caffeate, caffeic acid, kaempferol and cinnamic acid, respectively. Results for the desired ligand Interaction with protective antigen genes using SwissDock server showed that the caffeic acid had ΔG equals -9.10 kcal/mol and FullFitness equal to -993.16 kcal/mol respectively. The analysis of interaction between ligands with amino-acids of protective antigen indicated that the interaction of Caffeic acid whit Glutamic acid 117 had energy -15.5429 kcal/mol. Conclusion: Finding strong and safe inhibitors for anthrax toxin is very useful method for inhibiting its toxicity to cell. In this study the binding ability of four flavonoids to protective antigen was studied. Glutamic acid 117 is very effective

  1. [Poliovirus vaccine].

    Science.gov (United States)

    Shimizu, Hiroyuki

    2012-06-01

    To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world.

  2. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  3. Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.

    Science.gov (United States)

    Dumetz, Fabien; Jouvion, Grégory; Khun, Huot; Glomski, Ian Justin; Corre, Jean-Philippe; Rougeaux, Clémence; Tang, Wei-Jen; Mock, Michèle; Huerre, Michel; Goossens, Pierre Louis

    2011-06-01

    Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Development of a Zealand white rabbit deposition model to study inhalation anthrax

    Energy Technology Data Exchange (ETDEWEB)

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

    2016-01-28

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  5. Differential dependence on N-glycosylation of anthrax toxin receptors CMG2 and TEM8.

    Directory of Open Access Journals (Sweden)

    Sarah Friebe

    Full Text Available ANTXR 1 and 2, also known as TEM8 and CMG2, are two type I membrane proteins, which have been extensively studied for their role as anthrax toxin receptors, but with a still elusive physiological function. Here we have analyzed the importance of N-glycosylation on folding, trafficking and ligand binding of these closely related proteins. We find that TEM8 has a stringent dependence on N-glycosylation. The presence of at least one glycan on each of its two extracellular domains, the vWA and Ig-like domains, is indeed necessary for efficient trafficking to the cell surface. In the absence of any N-linked glycans, TEM8 fails to fold correctly and is recognized by the ER quality control machinery. Expression of N-glycosylation mutants reveals that CMG2 is less vulnerable to sugar loss. The absence of N-linked glycans in one of the extracellular domains indeed has little impact on folding, trafficking or receptor function of the wild type protein expressed in tissue culture cells. N-glycans do, however, seem required in primary fibroblasts from human patients. Here, the presence of N-linked sugars increases the tolerance to mutations in cmg2 causing the rare genetic disease Hyaline Fibromatosis Syndrome. It thus appears that CMG2 glycosylation provides a buffer towards genetic variation by promoting folding of the protein in the ER lumen.

  6. The secret life of the anthrax agent Bacillus anthracis: bacteriophage-mediated ecological adaptations.

    Directory of Open Access Journals (Sweden)

    Raymond Schuch

    2009-08-01

    Full Text Available Ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. A central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of Bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. Here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alterations in B. anthracis and the emergence of infected derivatives, or lysogens, with dramatically altered survival capabilities. Using both laboratory and environmental B. anthracis strains, we show that lysogeny can block or promote sporulation depending on the phage, induce exopolysaccharide expression and biofilm formation, and enable the long-term colonization of both an artificial soil environment and the intestinal tract of the invertebrate redworm, Eisenia fetida. All of the B. anthracis lysogens existed in a pseudolysogenic-like state in both the soil and worm gut, shedding phages that could in turn infect non-lysogenic B. anthracis recipients and confer survival phenotypes in those environments. Finally, the mechanism behind several phenotypic changes was found to require phage-encoded bacterial sigma factors and the expression of at least one host-encoded protein predicted to be involved in the colonization of invertebrate intestines. The results here demonstrate that during its environmental phase, bacteriophages provide B. anthracis with alternatives to sporulation that involve the activation of soil-survival and endosymbiotic capabilities.

  7. Development of a Zealand White Rabbit Deposition Model to Study Inhalation Anthrax

    Science.gov (United States)

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, A.P.; Corley, Richard A.

    2016-01-01

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID:26895308

  8. Fatal attraction: vegetation responses to nutrient inputs attract herbivores to infectious anthrax carcass sites.

    Science.gov (United States)

    Turner, Wendy C; Kausrud, Kyrre L; Krishnappa, Yathin S; Cromsigt, Joris P G M; Ganz, Holly H; Mapaure, Isaac; Cloete, Claudine C; Havarua, Zepee; Küsters, Martina; Getz, Wayne M; Stenseth, Nils Chr

    2014-11-22

    Parasites can shape the foraging behaviour of their hosts through cues indicating risk of infection. When cues for risk co-occur with desired traits such as forage quality, individuals face a trade-off between nutrient acquisition and parasite exposure. We evaluated how this trade-off may influence disease transmission in a 3-year experimental study of anthrax in a guild of mammalian herbivores in Etosha National Park, Namibia. At plains zebra (Equus quagga) carcass sites we assessed (i) carcass nutrient effects on soils and grasses, (ii) concentrations of Bacillus anthracis (BA) on grasses and in soils, and (iii) herbivore grazing behaviour, compared with control sites, using motion-sensing camera traps. We found that carcass-mediated nutrient pulses improved soil and vegetation, and that BA is found on grasses up to 2 years after death. Host foraging responses to carcass sites shifted from avoidance to attraction, and ultimately to no preference, with the strength and duration of these behavioural responses varying among herbivore species. Our results demonstrate that animal carcasses alter the environment and attract grazing hosts to parasite aggregations. This attraction may enhance transmission rates, suggesting that hosts are limited in their ability to trade off nutrient intake with parasite avoidance when relying on indirect cues. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  9. Peptide Probes Reveal a Hydrophobic Steric Ratchet in the Anthrax Toxin Protective Antigen Translocase.

    Science.gov (United States)

    Colby, Jennifer M; Krantz, Bryan A

    2015-11-06

    Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. Protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between the lethal factor amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide-clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides, and while these steric interactions may make a peptide translocate poorly, in the context of folded domains, they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Pharmacophore Selection and Redesign of Non-nucleotide Inhibitors of Anthrax Edema Factor

    Directory of Open Access Journals (Sweden)

    Maria Estrella Jimenez

    2012-11-01

    Full Text Available Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF, an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin’s basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera.

  11. Pharmacophore selection and redesign of non-nucleotide inhibitors of anthrax edema factor.

    Science.gov (United States)

    Schein, Catherine H; Chen, Deliang; Ma, Lili; Kanalas, John J; Gao, Jian; Jimenez, Maria Estrella; Sower, Laurie E; Walter, Mary A; Gilbertson, Scott R; Peterson, Johnny W

    2012-11-08

    Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin's basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC) in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera.

  12. Dried influenza vaccines : Over the counter vaccines

    NARCIS (Netherlands)

    Saluja, Vinay; Hinrichs, Wouter L. J.; Frijlink, Henderik W.

    2010-01-01

    Since last year influenza pandemic has struck again after 40 years, this is the right moment to discuss the different available formulation options for influenza vaccine. Looking back to the last 4 decades, most vaccines are still formulated as liquid solution. These vaccines have shown a poor

  13. Vaccines and Pregnancy

    Science.gov (United States)

    ... high or when infection would pose a high risk to the mother or baby, vaccination with a live vaccine is discussed. If there ... and benefits. For some diseases the benefit of vaccination outweighs any risks that may be associated with the vaccine. What ...

  14. History of vaccination.

    Science.gov (United States)

    Plotkin, Stanley

    2014-08-26

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  15. History of vaccination

    OpenAIRE

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  16. Mexico introduces pentavalent vaccine.

    Science.gov (United States)

    1999-08-01

    Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.

  17. Vaccines today, vaccines tomorrow: a perspective.

    Science.gov (United States)

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

  18. Isolation, Specification, Molecular Biology Assessment and Vaccine Development of Clostridium in Iran: A Review

    Directory of Open Access Journals (Sweden)

    Reza Pilehchian Langroudi

    2015-11-01

    Full Text Available Context: The genus Clostridium, which consists of spore-forming anaerobes, can cause different diseases in domestic animals and human and some of them are serious and fatal. According to the increasing economic value of the meat and milk-producing animals, the importance of a certain number of such diseases in Iran is unquestionable. Evidence Acquisition: In Iran, and probably in other Near East countries, much attention was formerly paid to control more serious contagious diseases, such as rinderpest, anthrax, etc. resulting in the negligence of diseases such as enterotoxaemia. The epizootiological position has now changed whereby some of the contagious diseases are eradicated or are being methodically controlled.Now it is time to care about the other problems such as clostridial diseases, which threaten the health of the sheep and cattle. It is impossible to eradicate these infectious microorganisms, since they are normally found in the soil and the intestinal contents of apparently healthy animals. Therefore, it is necessary to resort to vaccination which in some cases has given encouraging results. To avoid the losses from such infections it is necessary to have the best possible vaccination information, methodically and regularity of the susceptible animals. Conclusions: This review refers to the veterinary aspects of the anaerobic clostridial diseases and vaccine development concerning the works carried out in Iran and especially at the Razi Serum and Vaccine Research Institute in the last eight decades.

  19. Oral vaccination of fish

    OpenAIRE

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...

  20. Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

    OpenAIRE

    Wein, Alexander N.; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T.; Leppla, Stephen H.

    2012-01-01

    PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wild-type lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6,...

  1. Typhoid fever vaccination strategies.

    Science.gov (United States)

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by

  2. Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis.

    Science.gov (United States)

    Besschetnova, Tatiana Y; Ichimura, Takaharu; Katebi, Negin; St Croix, Brad; Bonventre, Joseph V; Olsen, Bjorn R

    2015-03-01

    It is well known that angiogenesis is linked to fibrotic processes in fibroproliferative diseases, but insights into pathophysiological processes are limited, due to lack of understanding of molecular mechanisms controlling endothelial and fibroblastic homeostasis. We demonstrate here that the matrix receptor anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial marker 8 (TEM8), is an essential component of these mechanisms. Loss of TEM8 function in mice causes reduced synthesis of endothelial basement membrane components and hyperproliferative and leaky blood vessels in skin. In addition, endothelial cell alterations in mutants are almost identical to those of endothelial cells in infantile hemangioma lesions, including activated VEGF receptor signaling in endothelial cells, increased expression of the downstream targets VEGF and CXCL12, and increased numbers of macrophages and mast cells. In contrast, loss of TEM8 in fibroblasts leads to increased rates of synthesis of fiber-forming collagens, resulting in progressive fibrosis in skin and other organs. Compromised interactions between TEM8-deficient endothelial and fibroblastic cells cause dramatic reduction in the activity of the matrix-degrading enzyme MMP2. In addition to insights into mechanisms of connective tissue homeostasis, our data provide molecular explanations for vascular and connective tissue abnormalities in GAPO syndrome, caused by loss-of-function mutations in ANTXR1. Furthermore, the loss of MMP2 activity suggests that fibrotic skin abnormalities in GAPO syndrome are, in part, the consequence of pathophysiological mechanisms underlying syndromes (NAO, Torg and Winchester) with multicentric skin nodulosis and osteolysis caused by homozygous loss-of-function mutations in MMP2. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  3. Vaccines: an ongoing promise?

    Science.gov (United States)

    Alsahli, M; Farrell, R J; Michetti, P

    2001-01-01

    Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

  4. Neurologic complications of vaccinations.

    Science.gov (United States)

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.

  5. Current Vaccine Shortages and Delays

    Science.gov (United States)

    ... Hepatitis A vaccine supply in the US. Updated Mar 2018 Note 2 : Pediatric hepatitis B vaccine: Merck ... Submitted, Licensed, and Recommended Vaccines & Biologics Red Book® Online Influenza Vaccination Recommendations Childhood & Adolescent Immunization Schedules Adult ...

  6. Vaccine-Preventable Disease Photos

    Science.gov (United States)

    ... Work Importance of Vaccines Paying for Vaccines State Immunization Programs Tips for Finding Vaccine Records Trusted Sources of ... efficacy, and use of vaccines within the broad immunization community of patients, parents, healthcare organizations, and government health agencies.

  7. Vaccines against poverty

    Science.gov (United States)

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

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

  8. Vaccine Associated Myocarditis

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2017-04-01

    Full Text Available Most of the cases of vaccine associated myocarditis have been following small pox vaccination. Reports have also been there after streptococcal pneumonia vaccine and influenza vaccine. In some cases, autoimmune/inflammatory syndrome induced by adjuvants (ASIA used in the vaccine have been implicated. Exclusion of other causes is very important in the diagnostic process, especially that of acute coronary syndrome. Management is similar to that of other etiologies of myocarditis. These rare instances of myocarditis should not preclude one from taking necessary immunization for vaccine preventable diseases.

  9. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax

    Science.gov (United States)

    Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S.

    2016-01-01

    The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. PMID:27431219

  11. Bacillus cereus Biovar Anthracis Causing Anthrax in Sub-Saharan Africa-Chromosomal Monophyly and Broad Geographic Distribution.

    Directory of Open Access Journals (Sweden)

    Kym S Antonation

    2016-09-01

    Full Text Available Through full genome analyses of four atypical Bacillus cereus isolates, designated B. cereus biovar anthracis, we describe a distinct clade within the B. cereus group that presents with anthrax-like disease, carrying virulence plasmids similar to those of classic Bacillus anthracis. We have isolated members of this clade from different mammals (wild chimpanzees, gorillas, an elephant and goats in West and Central Africa (Côte d'Ivoire, Cameroon, Central African Republic and Democratic Republic of Congo. The isolates shared several phenotypic features of both B. anthracis and B. cereus, but differed amongst each other in motility and their resistance or sensitivity to penicillin. They all possessed the same mutation in the regulator gene plcR, different from the one found in B. anthracis, and in addition, carry genes which enable them to produce a second capsule composed of hyaluronic acid. Our findings show the existence of a discrete clade of the B. cereus group capable of causing anthrax-like disease, found in areas of high biodiversity, which are possibly also the origin of the worldwide distributed B. anthracis. Establishing the impact of these pathogenic bacteria on threatened wildlife species will require systematic investigation. Furthermore, the consumption of wildlife found dead by the local population and presence in a domestic animal reveal potential sources of exposure to humans.

  12. Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel.

    Science.gov (United States)

    Wein, Alexander N; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T; Leppla, Stephen H

    2013-02-01

    PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an antimitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an antiangiogenesis therapy such as sunitinib or sorafinib.

  13. Vaccines today, vaccines tomorrow: a perspective

    OpenAIRE

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles M?rieux are known among experts only despite their contribution to global hea...

  14. Recent outbreak of cutaneous anthrax in Bangladesh: clinico-demographic profile and treatment outcome of cases attended at Rajshahi Medical College Hospital

    Directory of Open Access Journals (Sweden)

    Siddiqui Muhammad

    2012-08-01

    Full Text Available Abstract Background Human cutaneous anthrax results from skin exposure to B. anthracis, primarily due to occupational exposure. Bangladesh has experienced a number of outbreaks of cutaneous anthrax in recent years. The last episode occurred from April to August, 2011 and created mass havoc due to its dreadful clinical outcome and socio-cultural consequences. We report here the clinico-demographic profile and treatment outcome of 15 cutaneous anthrax cases attended at the Dermatology Outpatient Department of Rajshahi Medical College Hospital, Bangladesh between April and August, 2011 with an aim to create awareness for early case detection and management. Findings Anthrax was suspected primarily based on cutaneous manifestations of typical non-tender ulcer with black eschar, with or without oedema, and a history of butchering, or dressing/washing of cattle/goat or their meat. Diagnosis was established by demonstration of large gram-positive rods, typically resembling B. anthracis under light microscope where possible and also by ascertaining therapeutic success. The mean age of cases was 21.4 years (ranging from 3 to 46 years, 7 (46.7% being males and 8 (53.3% females. The majority of cases were from lower middle socioeconomic status. Types of exposures included butchering (20%, contact with raw meat (46.7%, and live animals (33.3%. Malignant pustule was present in upper extremity, both extremities, face, and trunk at frequencies of 11 (73.3%, 2 (13.3%, 1 (6.7% and 1 (6.7% respectively. Eight (53.3% patients presented with fever, 7 (46.7% had localized oedema and 5 (33.3% had regional lymphadenopathy. Anthrax was confirmed in 13 (86.7% cases by demonstration of gram-positive rods. All cases were cured with 2 months oral ciprofloxacin combined with flucoxacillin for 2 weeks. Conclusions We present the findings from this series of cases to reinforce the criteria for clinical diagnosis and to urge prompt therapeutic measures to treat

  15. Prevention, detection, and response to anthrax outbreak in Northern Tanzania using one health approach: A case study of Selela ward in Monduli district

    Directory of Open Access Journals (Sweden)

    Elibariki R. Mwakapeje

    2017-11-01

    Full Text Available Background: Anthrax is an infectious fatal zoonotic disease caused by Bacillus anthracis. Anthrax outbreak was confirmed in samples of wild animals following rumors of the outbreak in wild animals, livestock, and humans in Selela ward, Monduli district of Northern Tanzania. Therefore, a multi-sectorial team was deployed for outbreak response in the affected areas. Objectives: The aim of the response was to manage the outbreak in a One Health approach and specifically: (i To determine the magnitude of anthrax outbreak in humans, livestock, and wild animals in Selela ward, (ii to assess the outbreak local response capacity, (iii to establish mechanisms for safe disposal of animal carcasses in the affected areas, and (iv to mount effective control and preventive strategies using One Health approach in the affected areas. Materials and Methods: This was a cross-sectional field survey using: (i Active searching of suspected human cases at health facilities and community level, (ii physical counting and disposal of wild animal carcasses in the affected area, (iii collection of specimens from suspected human cases and animal carcasses for laboratory analysis, and (iv meetings with local animal and human health staff, political, and traditional leaders at local levels. We analyzed data by STATA software, and a map was created using Quantum GIS software. Results: A total of 21 humans were suspected, and most of them (62% being from Selela ward. The outbreak caused deaths of 10 cattle, 26 goats, and three sheep, and 131 wild animal carcasses were discarded the majority of them being wildebeest (83%. Based on laboratory results, three blood smears tested positive for anthrax using Giemsa staining while two wildebeest samples tested positive and five human blood samples tested negative for anthrax using quantitative polymerase chain reaction techniques. Clinical forms of anthrax were also observed in humans and livestock which suggest that wild animals may

  16. MMR Vaccine (Measles, Mumps, and Rubella)

    Science.gov (United States)

    Mumpsvax® Mumps Vaccine ... Biavax® II (as a combination product containing Mumps Vaccine, Rubella Vaccine) ... II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  17. What is a Preventive HIV Vaccine?

    Science.gov (United States)

    ... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ...

  18. Ethical and legal challenges of vaccines and vaccination: Reflections.

    Science.gov (United States)

    Jesani, Amar; Johari, Veena

    2017-01-01

    Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.

  19. The genome of a Bacillus isolate causing anthrax in chimpanzees combines chromosomal properties of B. cereus with B. anthracis virulence plasmids.

    Directory of Open Access Journals (Sweden)

    Silke R Klee

    Full Text Available Anthrax is a fatal disease caused by strains of Bacillus anthracis. Members of this monophyletic species are non motile and are all characterized by the presence of four prophages and a nonsense mutation in the plcR regulator gene. Here we report the complete genome sequence of a Bacillus strain isolated from a chimpanzee that had died with clinical symptoms of anthrax. Unlike classic B. anthracis, this strain was motile and lacked the four prohages and the nonsense mutation. Four replicons were identified, a chromosome and three plasmids. Comparative genome analysis revealed that the chromosome resembles those of non-B. anthracis members of the Bacillus cereus group, whereas two plasmids were identical to the anthrax virulence plasmids pXO1 and pXO2. The function of the newly discovered third plasmid with a length of 14 kbp is unknown. A detailed comparison of genomic loci encoding key features confirmed a higher similarity to B. thuringiensis serovar konkukian strain 97-27 and B. cereus E33L than to B. anthracis strains. For the first time we describe the sequence of an anthrax causing bacterium possessing both anthrax plasmids that apparently does not belong to the monophyletic group of all so far known B. anthracis strains and that differs in important diagnostic features. The data suggest that this bacterium has evolved from a B. cereus strain independently from the classic B. anthracis strains and established a B. anthracis lifestyle. Therefore we suggest to designate this isolate as "B. cereus variety (var. anthracis".

  20. Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to function.

    Directory of Open Access Journals (Sweden)

    Jianjun Sun

    Full Text Available BACKGROUND: Cell-surface receptors play essential roles in anthrax toxin action by providing the toxin with a high-affinity anchor and self-assembly site on the plasma membrane, mediating the toxin entry into cells through endocytosis, and shifting the pH threshold for prepore-to-pore conversion of anthrax toxin protective antigen (PA to a more acidic pH, thereby inhibiting premature pore formation. Each of the two known anthrax toxin receptors, ANTXR1 and ANTXR2, has an ectodomain comprised of an N-terminal von Willebrand factor A domain (VWA, which binds PA, and an uncharacterized immunoglobulin-like domain (Ig that connects VWA to the membrane-spanning domain. Potential roles of the receptor Ig domain in anthrax toxin action have not been investigated heretofore. METHODOLOGY/PRINCIPAL FINDINGS: We expressed and purified the ANTXR2 ectodomain (R2-VWA-Ig in E. coli and showed that it contains three disulfide bonds: one in R2-VWA and two in R2-Ig. Reduction of the ectodomain inhibited functioning of the pore, as measured by K(+ release from liposomes or Chinese hamster ovary cells or by PA-mediated translocation of a model substrate across the plasma membrane. However, reduction did not affect binding of the ectodomain to PA or the transition of ectodomain-bound PA prepore to the pore conformation. The inhibitory effect depended specifically on reduction of the disulfides within R2-Ig. CONCLUSIONS/SIGNIFICANCE: We conclude that disulfide integrity within R2-Ig is essential for proper functioning of receptor-bound PA pore. This finding provides a novel venue to investigate the mechanism of anthrax toxin action and suggests new strategies for inhibiting toxin action.

  1. A FRET-based high throughput screening assay to identify inhibitors of anthrax protective antigen binding to capillary morphogenesis gene 2 protein.

    Directory of Open Access Journals (Sweden)

    Michael S Rogers

    Full Text Available Anti-angiogenic therapies are effective for the treatment of cancer, a variety of ocular diseases, and have potential benefits in cardiovascular disease, arthritis, and psoriasis. We have previously shown that anthrax protective antigen (PA, a non-pathogenic component of anthrax toxin, is an inhibitor of angiogenesis, apparently as a result of interaction with the cell surface receptors capillary morphogenesis gene 2 (CMG2 protein and tumor endothelial marker 8 (TEM8. Hence, molecules that bind the anthrax toxin receptors may be effective to slow or halt pathological vascular growth. Here we describe development and testing of an effective homogeneous steady-state fluorescence resonance energy transfer (FRET high throughput screening assay designed to identify molecules that inhibit binding of PA to CMG2. Molecules identified in the screen can serve as potential lead compounds for the development of anti-angiogenic and anti-anthrax therapies. The assay to screen for inhibitors of this protein-protein interaction is sensitive and robust, with observed Z' values as high as 0.92. Preliminary screens conducted with a library of known bioactive compounds identified tannic acid and cisplatin as inhibitors of the PA-CMG2 interaction. We have confirmed that tannic acid both binds CMG2 and has anti-endothelial properties. In contrast, cisplatin appears to inhibit PA-CMG2 interaction by binding both PA and CMG2, and observed cisplatin anti-angiogenic effects are not mediated by interaction with CMG2. This work represents the first reported high throughput screening assay targeting CMG2 to identify possible inhibitors of both angiogenesis and anthrax intoxication.

  2. Laser facilitates vaccination

    Directory of Open Access Journals (Sweden)

    Ji Wang

    2016-01-01

    Full Text Available Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

  3. Vaccine Safety Datalink

    Science.gov (United States)

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  4. The HPV Vaccination Crisis

    Science.gov (United States)

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  5. Your child's first vaccines

    Science.gov (United States)

    ... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: drowsiness or temporary loss of appetite ( ...

  6. Your Baby's First Vaccines

    Science.gov (United States)

    ... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: Drowsiness or temporary loss of appetite ( ...

  7. Vaccines in Multiple Sclerosis.

    Science.gov (United States)

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    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.

  8. Vaccines and immunization

    African Journals Online (AJOL)

    Prof Ezechukwu

    vaccines for malaria and HIV infection. Despite the ... decades, effective vaccines against the major causes of ... challenge antibodies, specific helper and effector T lymphocytes ... materials to produced immunity to a disease. It was originally ...

  9. Pneumococcal Vaccines (PCV, PPSV)

    Science.gov (United States)

    ... Educators Search English Español Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth / For Parents / Your Child's Immunizations: ... cochlear implants. Why Are the PCV and PPSV Vaccines Recommended? Children younger than 2 years old, adults ...

  10. [Mumps vaccine virus transmission].

    Science.gov (United States)

    Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M

    2013-01-01

    In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.

  11. Rotavirus vaccines: an overview.

    OpenAIRE

    Midthun, K; Kapikian, A Z

    1996-01-01

    Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both...

  12. Vaccination: problems and perspectives.

    Directory of Open Access Journals (Sweden)

    S. M. Kharit

    2009-01-01

    Full Text Available Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.

  13. Oral vaccination of fish

    NARCIS (Netherlands)

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen

  14. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... previous dose of meningococcal vaccine, to the DTaP vaccine , or to latex If your child has a history of Guillain-Barré syndrome (a disease of the nervous system that causes progressive weakness), talk to your doctor about whether the vaccines are a good idea. Caring for Your Child ...

  15. Hepatitis A Vaccine

    Science.gov (United States)

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Why get vaccinated against hepatitis A?Hepatitis A is a serious liver disease. It is caused by the hepatitis A virus (HAV). HAV is spread from ...

  16. Evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses.

    Science.gov (United States)

    Grinshpun, Sergey A; Weber, Angela M; Yermakov, Michael; Indugula, Reshmi; Elmashae, Yousef; Reponen, Tiina; Rose, Laura

    2017-08-01

    Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B. anthracis spores. The study was designed to (1) evaluate the performance of four filter types (one mixed cellulose ester, MCE (pore size = 3 µm), two polytetrafluoroethylene, PTFE (1 and 3 µm), and one polycarbonate, PC (3 µm)); and (2) evaluate the best performing filters in two commercially available inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The filters were assessed based on criteria such as ability to maintain low pressure drop over an extended sampling period, filter integrity under various environmental conditions, spore collection and extraction efficiencies, ease of loading and unloading the filters into the samplers, cost, and availability. Three of the four tested collection filters-except MCE-were found suitable for efficient collection and recovery of Bt(k) spores sampled from dry and humid as well as dusty and clean air environments for up to 8 hr. The PC (3 µm) filter was identified as the best performing filter in this study. The PTFE (3 µm) demonstrated a comparable performance, but it is more expensive. Slightly higher concentrations were measured with the IOM inhalable sampler which is the preferred sampler's performance criterion when detecting a highly pathogenic agent with no established "safe" inhalation exposure level. Additional studies are needed to address the effects of

  17. Sustainable vaccine development: a vaccine manufacturer's perspective.

    Science.gov (United States)

    Rappuoli, Rino; Hanon, Emmanuel

    2018-05-08

    Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health. Copyright © 2018 GlaxoSmithKine Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  18. Impact of Dendrimer Terminal Group Chemistry on Blockage of the Anthrax Toxin Channel: A Single Molecule Study.

    Science.gov (United States)

    Yamini, Goli; Kalu, Nnanya; Nestorovich, Ekaterina M

    2016-11-15

    Nearly all the cationic molecules tested so far have been shown to reversibly block K⁺ current through the cation-selective PA 63 channels of anthrax toxin in a wide nM-mM range of effective concentrations. A significant increase in channel-blocking activity of the cationic compounds was achieved when multiple copies of positively charged ligands were covalently linked to multivalent scaffolds, such as cyclodextrins and dendrimers. Even though multivalent binding can be strong when the individual bonds are relatively weak, for drug discovery purposes we often strive to design multivalent compounds with high individual functional group affinity toward the respective binding site on a multivalent target. Keeping this requirement in mind, here we perform a single-channel/single-molecule study to investigate kinetic parameters of anthrax toxin PA 63 channel blockage by second-generation (G2) poly(amido amine) (PAMAM) dendrimers functionalized with different surface ligands, including G2-NH₂, G2-OH, G2-succinamate, and G2-COONa. We found that the previously reported difference in IC 50 values of the G2-OH/PA 63 and G2-NH₂/PA 63 binding was determined by both on- and off-rates of the reversible dendrimer/channel binding reaction. In 1 M KCl, we observed a decrease of about three folds in k o n and a decrease of only about ten times in t r e s with G2-OH compared to G2-NH₂. At the same time for both blockers, k o n and t r e s increased dramatically with transmembrane voltage increase. PAMAM dendrimers functionalized with negatively charged succinamate, but not carboxyl surface groups, still had some residual activity in inhibiting the anthrax toxin channels. At 100 mV, the on-rate of the G2-succinamate binding was comparable with that of G2-OH but showed weaker voltage dependence when compared to G2-OH and G2-NH₂. The residence time of G2-succinamate in the channel exhibited opposite voltage dependence compared to G2-OH and G2-NH₂, increasing with the cis

  19. Peptide Vaccines for Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Rory C. F. De Brito

    2018-05-01

    Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  20. Peptide Vaccines for Leishmaniasis.

    Science.gov (United States)

    De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

    2018-01-01

    Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  1. Vaccines as Epidemic Insurance.

    Science.gov (United States)

    Pauly, Mark V

    2017-10-27

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

  2. Vaccines as Epidemic Insurance

    Directory of Open Access Journals (Sweden)

    Mark V. Pauly

    2017-10-01

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

  3. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its...

  4. vaccination with newcastle disease vaccines strain i2 and lasota

    African Journals Online (AJOL)

    UP Employee

    mash feed as vaccine carriers was conducted. Newcastle disease vaccine strain I2 and. NDV La Sota vaccines provided protection to commercial and local chickens vaccinated through i/o, i/m or dw. No significant difference (P≤0.05) was observed in the antibody titre of commercial or local chickens vaccinated with either ...

  5. One-pot synthesis of strongly fluorescent DNA-CuInS2 quantum dots for label-free and ultrasensitive detection of anthrax lethal factor DNA

    International Nuclear Information System (INIS)

    Liu, Ziping; Su, Xingguang

    2016-01-01

    Herein, high quality DNA-CuInS 2 QDs are facilely synthesized through a one-pot hydrothermal method with fluorescence quantum yield as high as 23.4%, and the strongly fluorescent DNA-CuInS 2 QDs have been utilized as a novel fluorescent biosensor for label-free and ultrasensitive detection of anthrax lethal factor DNA. L-Cysteine (L-Cys) and a specific-sequence DNA are used as co-ligands to stabilize the CuInS 2 QDs. The specific-sequence DNA consists of two domains: phosphorothiolates domain (sulfur-containing variants of the usual phosphodiester backbone) controls the nanocrystal passivation and serves as a ligand, and the functional domain (non-phosphorothioates) controls the biorecognition. The as-prepared DNA-CuInS 2 QDs have high stability, good water-solubility and low toxicity. Under the optimized conditions, a linear correlation was established between the fluorescence intensity ratio I/I 0 (I 0 is the original fluorescence intensity of DNA-CuInS 2 QDs, and I is the fluorescence intensity of DNA-CuInS 2 QDs/GO with the addition of various concentrations of anthrax lethal factor DNA) and the concentration of anthrax lethal factor DNA in the range of 0.029–0.733 nmol L −1 with a detection limit of 0.013 nmol L −1 . The proposed method has been successfully applied to the determination of anthrax lethal factor DNA sequence in human serum samples with satisfactory results. Because of low toxicity and fine biocompatibility, DNA-CuInS 2 QDs also hold potential applications in bioimaging. - Highlights: • Strongly fluorescent DNA-QDs were successfully prepared by a one-pot hydrothermal method with quantum yield up to 23.4%. • A biosensor for label-free detection of anthrax lethal factor DNA was established based on the as-prepared DNA-QDs. • The DNA sensor took advantage of the feature that ssDNA binds to GO with significantly higher affinity than dsDNA. • Good sensitivity and selectivity were obtained. • This method was utilized to detect

  6. One-pot synthesis of strongly fluorescent DNA-CuInS{sub 2} quantum dots for label-free and ultrasensitive detection of anthrax lethal factor DNA

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ziping; Su, Xingguang, E-mail: suxg@jlu.edu.cn

    2016-10-26

    Herein, high quality DNA-CuInS{sub 2} QDs are facilely synthesized through a one-pot hydrothermal method with fluorescence quantum yield as high as 23.4%, and the strongly fluorescent DNA-CuInS{sub 2} QDs have been utilized as a novel fluorescent biosensor for label-free and ultrasensitive detection of anthrax lethal factor DNA. L-Cysteine (L-Cys) and a specific-sequence DNA are used as co-ligands to stabilize the CuInS{sub 2} QDs. The specific-sequence DNA consists of two domains: phosphorothiolates domain (sulfur-containing variants of the usual phosphodiester backbone) controls the nanocrystal passivation and serves as a ligand, and the functional domain (non-phosphorothioates) controls the biorecognition. The as-prepared DNA-CuInS{sub 2} QDs have high stability, good water-solubility and low toxicity. Under the optimized conditions, a linear correlation was established between the fluorescence intensity ratio I/I{sub 0} (I{sub 0} is the original fluorescence intensity of DNA-CuInS{sub 2} QDs, and I is the fluorescence intensity of DNA-CuInS{sub 2} QDs/GO with the addition of various concentrations of anthrax lethal factor DNA) and the concentration of anthrax lethal factor DNA in the range of 0.029–0.733 nmol L{sup −1} with a detection limit of 0.013 nmol L{sup −1}. The proposed method has been successfully applied to the determination of anthrax lethal factor DNA sequence in human serum samples with satisfactory results. Because of low toxicity and fine biocompatibility, DNA-CuInS{sub 2} QDs also hold potential applications in bioimaging. - Highlights: • Strongly fluorescent DNA-QDs were successfully prepared by a one-pot hydrothermal method with quantum yield up to 23.4%. • A biosensor for label-free detection of anthrax lethal factor DNA was established based on the as-prepared DNA-QDs. • The DNA sensor took advantage of the feature that ssDNA binds to GO with significantly higher affinity than dsDNA. • Good sensitivity and selectivity were

  7. Addressing the Federal-State-Local Interface Issues During a Catastrophic Event Such as an Anthrax Attack

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Steven L.; Lesperance, Ann M.; Upton, Jaki F.

    2010-02-01

    On October 9, 2008, federal, state and local policy makers, emergency managers, and medical and public health officials convened in Seattle, Washington, for a workshop on Addressing the Federal-State-Local Interface Issues During a Catastrophic Event Such as an Anthrax Attack. The day-long symposium was aimed at generating a dialogue about recovery and restoration through a discussion of the associated challenges that impact entire communities, including people, infrastructure, and critical systems. The Principal Federal Official (PFO) provided an overview of the role of the PFO in a catastrophic event. A high-level summary of an anthrax scenario was presented. The remainder of the day was focused on interactive discussions among federal, state and local emergency management experts in the areas of: • Decision-making, prioritization, and command and control • Public health/medical services • Community resiliency and continuity of government. Key topics and issues that resulted from discussions included: • Local representation in the Joint Field Office (JFO) • JFO transition to the Long-Term Recovery Office • Process for prioritization of needs • Process for regional coordination • Prioritization - process and federal/military intervention • Allocation of limited resources • Re-entry decision and consistency • Importance of maintaining a healthy hospital system • Need for a process to establish a consensus on when it is safe to re-enter. This needs to be across all jurisdictions including the military. • Insurance coverage for both private businesses and individuals • Interaction between the government and industry. The symposium was sponsored by the Interagency Biological Restoration Demonstration, a collaborative regional program jointly funded by the U.S. Department of Homeland Security and the U.S. Department of Defense. To aid the program’s efforts and inform the development of blueprint for recovery from a biological incident

  8. Current Ebola vaccines

    Science.gov (United States)

    Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

    2012-01-01

    Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078

  9. Vaccines in a hurry.

    Science.gov (United States)

    Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben

    2009-05-26

    Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

  10. Vaccine strategies: Optimising outcomes.

    Science.gov (United States)

    Hardt, Karin; Bonanni, Paolo; King, Susan; Santos, Jose Ignacio; El-Hodhod, Mostafa; Zimet, Gregory D; Preiss, Scott

    2016-12-20

    Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the

  11. The Meningitis Vaccine Project.

    Science.gov (United States)

    LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

    2007-09-03

    Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.

  12. 75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

    Science.gov (United States)

    2010-08-11

    ... Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention... information materials for rotavirus vaccine. DATES: Written comments are invited and must be received on or... (chickenpox), pneumococcal conjugate, rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and...

  13. Vaccine process technology.

    Science.gov (United States)

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  14. A Retrospective Study on the Epidemiology of Anthrax, Foot and Mouth Disease, Haemorrhagic Septicaemia, Peste des Petits Ruminants and Rabies in Bangladesh, 2010-2012

    Science.gov (United States)

    Mondal, Shankar P.; Yamage, Mat

    2014-01-01

    Anthrax, foot and mouth disease (FMD), haemorrhagic septicaemia (HS), peste des petits ruminants (PPR) and rabies are considered to be endemic in Bangladesh. This retrospective study was conducted to understand the geographic and seasonal distribution of these major infectious diseases in livestock based on data collected through passive surveillance from 1 January 2010 to 31 December 2012. Data analysis for this period revealed 5,937 cases of anthrax, 300,333 of FMD, 13,436 of HS, 247,783 of PPR and 14,085 cases of dog bite/rabies. While diseases were reported in almost every district of the country, the highest frequency of occurrence corresponded to the susceptible livestock population in the respective districts. There was no significant difference in the disease occurrences between districts bordering India/Myanmar and non-border districts (p>0.05). Significantly higher (pBangladesh. PMID:25101836

  15. Perturbing Tandem Energy Transfer in Luminescent Heterobinuclear Lanthanide Coordination Polymer Nanoparticles Enables Real-Time Monitoring of Release of the Anthrax Biomarker from Bacterial Spores.

    Science.gov (United States)

    Gao, Nan; Zhang, Yunfang; Huang, Pengcheng; Xiang, Zhehao; Wu, Fang-Ying; Mao, Lanqun

    2018-06-05

    Lanthanide-based luminescent sensors have been widely used for the detection of the anthrax biomarker dipicolinic acid (DPA). However, mainly based on DPA sensitization to the lanthanide core, most of them failed to realize robust detection of DPA in bacterial spores. We proposed a new strategy for reliable detection of DPA by perturbing a tandem energy transfer in heterobinuclear lanthanide coordination polymer nanoparticles simply constructed by two kinds of lanthanide ions, Tb 3+ and Eu 3+ , and guanosine 5'-monophosphate. This smart luminescent probe was demonstrated to exhibit highly sensitive and selective visual luminescence color change upon exposure to DPA, enabling accurate detection of DPA in complex biosystems such as bacterial spores. DPA release from bacterial spores on physiological germination was also successfully monitored in real time by confocal imaging. This probe is thus expected to be a powerful tool for efficient detection of bacterial spores in responding to anthrax threats.

  16. Vaccination against seasonal flu

    CERN Multimedia

    2015-01-01

    The Medical Service once again recommends you to get your annual flu vaccination for the year.   Vaccination is the most effective way of avoiding the illness and any serious consequences and protecting those around you. The flu can have especially serious consequences for people with chronic conditions (diabetes, cardio-vascular disease, etc.), pregnant women, infants, and people over 65 years of age. Remember, anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor) with their vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement by UNIQA. NB: The Medical Service cannot provide this vaccination service for family members or retired members of the personnel. For more information: • The "Seasonal flu" flyer by the Medical Service • Recommendations of the Swiss Federal Office of Public...

  17. Prophylactic Hepatitis E Vaccine.

    Science.gov (United States)

    Zhang, Jun; Zhao, Qinjian; Xia, Ningshao

    2016-01-01

    Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012.

  18. Vaccination and neurological disorders

    Directory of Open Access Journals (Sweden)

    Anastasia Gkampeta

    2015-12-01

    Full Text Available Active immunization of children has been proven very effective in elimination of life threatening complications of many infectious diseases in developed countries. However, as vaccination-preventable infectious diseases and their complications have become rare, the interest focuses on immunization-related adverse reactions. Unfortunately, fear of vaccination-related adverse effects can led to decreased vaccination coverage and subsequent epidemics of infectious diseases. This review includes reports about possible side effects following vaccinations in children with neurological disorders and also published recommendations about vaccinating children with neurological disorders. From all international published data anyone can conclude that vaccines are safer than ever before, but the challenge remains to convey this message to society.

  19. Vaccines and Kawasaki disease.

    Science.gov (United States)

    Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

    2016-01-01

    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.

  20. Vaccine development for syphilis.

    Science.gov (United States)

    Lithgow, Karen V; Cameron, Caroline E

    2017-01-01

    Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.

  1. The Latest in Vaccine Policies: Selected Issues in School Vaccinations, Healthcare Worker Vaccinations, and Pharmacist Vaccination Authority Laws.

    Science.gov (United States)

    Barraza, Leila; Schmit, Cason; Hoss, Aila

    2017-03-01

    This paper discusses recent changes to state legal frameworks for mandatory vaccination in the context of school and healthcare worker vaccination. It then discusses state laws that allow pharmacists the authority to vaccinate.

  2. Needle-free influenza vaccination

    NARCIS (Netherlands)

    Amorij, Jean-Pierre; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan C.; Huckriede, Anke

    2010-01-01

    Vaccination is the cornerstone of influenza control in epidemic and pandemic situations. Influenza vaccines are typically given by intramuscular injection. However, needle-free vaccinations could offer several distinct advantages over intramuscular injections: they are pain-free, easier to

  3. What Vaccines Do You Need?

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics The Adult Vaccine Quiz Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Vaccines are recommended for adults based on age, health ...

  4. Recommended Vaccines for Healthcare Workers

    Science.gov (United States)

    ... Vaccination Resources for Healthcare Professionals Recommended Vaccines for Healthcare Workers Recommend on Facebook Tweet Share Compartir On ... for More Information Resources for Those Vaccinating HCWs Healthcare workers (HCWs) are at risk for exposure to ...

  5. Vaccination via Chloroplast Genetics: Affordable Protein Drugs for the Prevention and Treatment of Inherited or Infectious Human Diseases.

    Science.gov (United States)

    Daniell, Henry; Chan, Hui-Ting; Pasoreck, Elise K

    2016-11-23

    Plastid-made biopharmaceuticals treat major metabolic or genetic disorders, including Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy. Booster vaccines made in chloroplasts prevent global infectious diseases, such as tuberculosis, malaria, cholera, and polio, and biological threats, such as anthrax and plague. Recent advances in this field include commercial-scale production of human therapeutic proteins in FDA-approved cGMP facilities, development of tags to deliver protein drugs to targeted human cells or tissues, methods to deliver precise doses, and long-term stability of protein drugs at ambient temperature, maintaining their efficacy. Codon optimization utilizing valuable information from sequenced chloroplast genomes enhanced expression of eukaryotic human or viral genes in chloroplasts and offered unique insights into translation in chloroplasts. Support from major biopharmaceutical companies, development of hydroponic production systems, and evaluation by regulatory agencies, including the CDC, FDA, and USDA, augur well for advancing this novel concept to the clinic and revolutionizing affordable healthcare.

  6. Rotavirus vaccines and vaccination in Latin America

    Directory of Open Access Journals (Sweden)

    Linhares Alexandre C.

    2000-01-01

    Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be

  7. Rotavirus vaccines and vaccination in Latin America

    Directory of Open Access Journals (Sweden)

    Alexandre C. Linhares

    2000-11-01

    Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be

  8. Pricing of new vaccines

    OpenAIRE

    Lee, Bruce Y; McGlone, Sarah M

    2010-01-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine targe...

  9. Underutilization of Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Marshall K. Cheney

    2013-04-01

    Full Text Available Yearly influenza vaccination continues to be underutilized by those who would most benefit from it. The Health Belief Model was used to explain differences in beliefs about influenza vaccination among at-risk individuals resistant to influenza vaccination. Survey data were collected from 74 members of at-risk groups who were not vaccinated for influenza during the previous flu season. Accepting individuals were more likely to perceive flu as a threat to health and perceive access barriers, and cues to action were the most important influence on whether they plan to get vaccinated. In comparison, resistant individuals did not feel threatened by the flu, access barriers were not a problem, and they did not respond favorably to cues to action. Perceived threat, perceived access barriers, and cues to action were significantly associated with plans to be vaccinated for influenza in the next flu season. Participants who saw influenza as a threat to their health had 5.4 times the odds of planning to be vaccinated than those who did not. Participants reporting barriers to accessing influenza vaccination had 7.5 times the odds of reporting plans to be vaccinated. Those responding positively to cues to action had 12.2 times the odds of planning to be vaccinated in the next flu season than those who did not. Accepting and resistant individuals have significant differences in their beliefs, which require different intervention strategies to increase vaccination rates. These findings provide important information to researchers and practitioners working to increase influenza vaccination rates.

  10. Respiratory Syncytial Virus Vaccines

    OpenAIRE

    Dudas, Robert A.; Karron, Ruth A.

    1998-01-01

    Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically d...

  11. PREDICTION OF AEROSOL HAZARDS ARISING FROM THE OPENING OF AN ANTHRAX-TAINTED LETTER IN AN OPEN OFFICE ENVIRONMENT USING COMPUTATIONAL FLUID DYNAMICS

    Directory of Open Access Journals (Sweden)

    FUE-SANG LIEN

    2010-09-01

    Full Text Available Early experimental work, conducted at Defence R&D Canada–Suffield, measured and characterized the personal and environmental contamination associated with simulated anthrax-tainted letters under a number of different scenarios in order to obtain a better understanding of the physical and biological processes for detecting, assessing, and formulating potential mitigation strategies for managing the risks associated with opening an anthrax-tainted letter. These experimental investigations have been extended in the present study to simulate numerically the contamination from the opening of anthrax-tainted letters in an open office environment using computational fluid dynamics (CFD. A quantity of 0.1 g of Bacillus atropheus (formerly referred to as Bacillus subtilis var globigii (BG spores in dry powder form, which was used here as a surrogate species for Bacillus anthracis (anthrax, was released from an opened letter in the experiment. The accuracy of the model for prediction of the spatial distribution of BG spores in the office from the opened letter is assessed qualitatively (and to the extent possible, quantitatively by detailed comparison with measured BG concentrations obtained under a number of different scenarios, some involving people moving within the office. The observed discrepancy between the numerical predictions and experimental measurements of concentration was probably the result of a number of physical processes which were not accounted for in the numerical simulation. These include air flow leakage from cracks and crevices of the building shell; the dispersion of BG spores in the Heating, Ventilation, and Air Conditioning (HVAC system; and, the effect of deposition and re-suspension of BG spores from various surfaces in the office environment.

  12. Analysing the spatial patterns of livestock anthrax in Kazakhstan in relation to environmental factors: a comparison of local (Gi* and morphology cluster statistics

    Directory of Open Access Journals (Sweden)

    Ian T. Kracalik

    2012-11-01

    Full Text Available We compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle and small (sheep and goats domestic ruminants across Kazakhstan. The Getis-Ord (Gi* statistic and a multidirectional optimal ecotope algorithm (AMOEBA were compared using 1st, 2nd and 3rd order Rook contiguity matrices. Multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the AMOEBA and Gi* tests. A logistic regression was used to define a risk surface for anthrax outbreaks and to compare agreement between clustering methodologies. Tests revealed differences in the spatial distribution of clusters as well as the total number of clusters in large ruminants for AMOEBA (n = 149 and for small ruminants (n = 9. In contrast, Gi* revealed fewer large ruminant clusters (n = 122 and more small ruminant clusters (n = 61. Significant environmental differences were found between groups using the Kruskall-Wallis and Mann- Whitney U tests. Logistic regression was used to model the presence/absence of anthrax outbreaks and define a risk surface for large ruminants to compare with cluster analyses. The model predicted 32.2% of the landscape as high risk. Approximately 75% of AMOEBA clusters corresponded to predicted high risk, compared with ~64% of Gi* clusters. In general, AMOEBA predicted more irregularly shaped clusters of outbreaks in both livestock groups, while Gi* tended to predict larger, circular clusters. Here we provide an evaluation of both tests and a discussion of the use of each to detect environmental conditions associated with anthrax outbreak clusters in domestic livestock. These findings illustrate important differences in spatial statistical methods for defining local clusters and highlight the importance of selecting appropriate levels of data aggregation.

  13. Vaccines, our shared responsibility.

    Science.gov (United States)

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Vaccines: Shaping global health.

    Science.gov (United States)

    Pagliusi, Sonia; Ting, Ching-Chia; Lobos, Fernando

    2017-03-14

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines' access, and of the importance of new public-private partnerships. Copyright © 2017.

  15. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    Science.gov (United States)

    Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  16. Clinical development of Ebola vaccines

    Science.gov (United States)

    Sridhar, Saranya

    2015-01-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  17. The Human Hookworm Vaccine.

    Science.gov (United States)

    Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K

    2013-04-18

    Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Pricing of new vaccines.

    Science.gov (United States)

    Lee, Bruce Y; McGlone, Sarah M

    2010-08-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.

  19. Pricing of new vaccines

    Science.gov (United States)

    McGlone, Sarah M

    2010-01-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; (4) Quantify the incremental value of the new vaccine's characteristics; (5) Determine vaccine positioning in the marketplace; (6) Estimate the vaccine price-demand curve; (7) Calculate vaccine costs (including those of manufacturing, distribution, and research and development); (8) Account for various legal, regulatory, third party payer and competitor factors; (9) Consider the overall product portfolio; (10) Set pricing objectives; (11) Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area. PMID:20861678

  20. Acceptance of vaccination

    NARCIS (Netherlands)

    Lehmann, B.; Eilers, R.; Donken, R.; Barug, D.; Swillens, J.; Vriend, C. de; Weerdenburg, S.; Pot, M.; Keulen, H. van; Paulussen, T.; Vermey, K.; Alberts, N.; Marra, E.; Melker, H.E. de; Mollema, L.

    2016-01-01

    Both in 2013 and 2015 the mean intention of parents to vaccinate their child was high. Only 21% of parents reported making an informed decision about childhood vaccinations included in the NIP. Mass media attention on the use of allegedly inferior needles, which was later refuted, appeared to have a

  1. Vaccines Stop Illness

    Science.gov (United States)

    ... the disease no longer exists. If we keep vaccinating now, parents in the future may be able to trust that diseases like polio and meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about ...

  2. Chimeric Pestivirus Experimental Vaccines.

    Science.gov (United States)

    Reimann, Ilona; Blome, Sandra; Beer, Martin

    2016-01-01

    Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics.

  3. Vaccination Perceptions of College Students: With and without Vaccination Waiver.

    Science.gov (United States)

    Jadhav, Emmanuel D; Winkler, Danielle L; Anderson, Billie S

    2018-01-01

    The 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. Young 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. A 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. Young 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.

  4. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup

    2010-01-01

    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...

  5. Financing children's vaccines.

    Science.gov (United States)

    Nelson, E Anthony S; Sack, David; Wolfson, Lara; Walker, Damian G; Seng, Lim Fong; Steele, Duncan

    2009-11-20

    A 2006 Commonwealth Association of Paediatric Gastroenterology and Nutrition workshop on financing children's vaccines highlighted the potential for vaccines to control diarrhoea and other diseases as well as spur economic development through better health. Clear communication of vaccination value to decision-makers is required, together with sustainable funding mechanisms. GAVI and partners have made great progress providing funding for vaccines for children in the poorest countries but other solutions may be required to achieve the same gains in middle- and high-income countries. World Health Organization has a wealth of freely available country-level data on immunisation that academics and advocates can use to communicate the economic and health benefits of vaccines to decision-makers.

  6. Next generation vaccines.

    Science.gov (United States)

    Riedmann, Eva M

    2011-07-01

    In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.

  7. HIV vaccines: new frontiers in vaccine development.

    Science.gov (United States)

    Duerr, Ann; Wasserheit, Judith N; Corey, Lawrence

    2006-08-15

    A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.

  8. Laser vaccine adjuvants

    Science.gov (United States)

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    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

  9. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  10. Chloroplast-Derived Vaccine Antigens and Biopharmaceuticals: Expression, Folding, Assembly and Functionality

    Science.gov (United States)

    Chebolu, S.; Daniell, H.

    2009-01-01

    Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance, and multi-gene expression in a single transformation event. Oral delivery is facilitated by hyperexpression of vaccine antigens against cholera, tetanus, anthrax, plague, or canine parvovirus (4%–31% of total soluble protein, TSP) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato) as well as the availability of antibiotic free selectable markers or the ability to excise selectable marker genes. Hyperexpression of several therapeutic proteins, including human serum albumin (11.1% TSP), somatotropin (7% TSP), interferon-alpha (19% TSP), interferon-gamma (6% TSP), and antimicrobial peptide (21.5% TSP), facilitates efficient and economic purification. Also, the presence of chaperones and enzymes in chloroplasts facilitates assembly of complex multisubunit proteins and correct folding of human blood proteins with proper disulfide bonds. Functionality of chloroplast-derived vaccine antigens and therapeutic proteins has been demonstrated by several assays, including the macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLA cells or human lung carcinoma cells against encephalomyocarditis virus, systemic immune response, protection against pathogen challenge, and growth or inhibition of cell cultures. Purification of human proinsulin has been achieved using novel purification strategies (inverse temperature transition property) that do not require expensive column chromatography techniques. Thus, transgenic chloroplasts are ideal bioreactors for production of functional human and animal therapeutic proteins in an environmentally friendly manner. PMID:19401820

  11. Vaccination in food allergic patients

    African Journals Online (AJOL)

    Most people do not react to vaccination and the incidence of vaccine anaphylaxis is estimated to be <1/million for all vaccines.[1] Most anaphylactic reactions occur in non-food allergic children. It is strongly recommended that anyone admin- istering vaccines has resuscitation equipment available to manage potential ...

  12. Parental knowledge of paediatric vaccination

    Directory of Open Access Journals (Sweden)

    Borràs Eva

    2009-05-01

    Full Text Available Abstract Background Although routine vaccination is a major tool in the primary prevention of some infectious diseases, there is some reluctance in a proportion of the population. Negative parental perceptions of vaccination are an important barrier to paediatric vaccination. The aim of this study was to investigate parental knowledge of paediatric vaccines and vaccination in Catalonia. Methods A retrospective, cross-sectional study was carried out in children aged Results An association was observed between greater vaccination coverage of the 4:4:4:3:1 schedule (defined as: 4 DTPa/w doses, 4 Hib doses, 4 OPV doses, 3 MenC doses and 1 MMR dose and maternal age >30 years (OR: 2.30; 95% CI: 1.20–4.43 and with a knowledge of vaccination score greater than the mean (OR: 0.45; 95% CI: 0.28–0.72. The score increased with maternal educational level and in parents of vaccinated children. A total of 20.47% of parents stated that vaccines could have undesirable consequences for their children. Of these, 23.26% had no specific information and 17.83% stated that vaccines can cause adverse reactions and the same percentage stated that vaccines cause allergies and asthma. Conclusion Higher vaccination coverage is associated with older maternal age and greater knowledge of vaccination. Vaccination coverage could be raised by improving information on vaccines and vaccination.

  13. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN.

    Science.gov (United States)

    He, Yongqun; Xiang, Zuoshuang

    2010-09-27

    Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines

  14. [Current events in vaccination].

    Science.gov (United States)

    Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C

    2011-11-01

    The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

  15. Technical Transformation of Biodefense Vaccines

    Science.gov (United States)

    Lu, Shan; Wang, Shixia

    2013-01-01

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

  16. Progress towards a Leishmania vaccine.

    Science.gov (United States)

    Tabbara, Khaled S

    2006-07-01

    Leishmaniasis is a vector-born protozoan disease. Approximately 12 million individuals are affected worldwide with an estimated annual incidence of 1.5-2 million. Two clinical manifestations are recognized, cutaneous, and visceral, both of which are common in the Middle East. In both forms, infection is chronic, with potential deformities, persistence following cure, and lifelong risk of reactivation. Attempts to develop an effective human Leishmania vaccine have not yet succeeded. Leishmanization, a crude form of live vaccination historically originated in this part of the world. Experimental vaccination has been extensively studied in model animals in the past 2 decades. In this review, major human killed vaccine trials are surveyed, and modern trends in Leishmania vaccine development, including subunit vaccines, naked DNA vaccines, and transmission blocking vaccines are explored. Recent findings of a link between persistence of live parasites, and maintenance of long-term immunity suggest live vaccination with attenuated strains, as a future vaccination strategy.

  17. [Development of current smallpox vaccines].

    Science.gov (United States)

    Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N

    2011-01-01

    The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.

  18. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  19. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, M; Met, Ö; Svane, I M

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  20. ADE and dengue vaccination.

    Science.gov (United States)

    Martínez-Vega, Ruth Aralí; Carrasquila, Gabriel; Luna, Expedito; Ramos-Castañeda, José

    2017-07-13

    The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-08-12

    Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valuepost delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd

  2. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...

  3. [Development of new vaccines].

    Science.gov (United States)

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

    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.

  4. Ingredients of Vaccines

    Science.gov (United States)

    ... containing preservative that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria. For children with a prior history of allergic reactions to any of these substances ...

  5. Current status of rotavirus vaccines.

    Science.gov (United States)

    Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong

    2015-11-01

    Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.

  6. Vaccines for Older Adults.

    Science.gov (United States)

    Worz, Chad; Martin, Caren McHenry; Travis, Catherine

    2017-09-01

    Several vaccine-preventable diseases-influenza, pneumonia, herpes zoster, and pertussis-threaten the health of older adults in the United States. Both the costs associated with treating these diseases and the potential to increase morbidity and mortality are high for this patient population. Pharmacists and other health care professionals play a significant role in ensuring the elderly patient receives the recommended vaccines at the recommended intervals.

  7. Beninese vaccination clinic

    OpenAIRE

    Linda Sun

    2017-01-01

    This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

  8. Beninese vaccination clinic

    Directory of Open Access Journals (Sweden)

    Linda Sun

    2017-04-01

    Full Text Available This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

  9. HPV vaccines: a controversial issue?

    Science.gov (United States)

    Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W

    2016-01-01

    Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  10. Epilepsy and vaccinations: Italian guidelines.

    Science.gov (United States)

    Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto

    2013-10-01

    Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  11. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  12. Key Facts about Seasonal Flu Vaccine

    Science.gov (United States)

    ... Swine Variant Pandemic Other Key Facts About Seasonal Flu Vaccine Language: English (US) Español Recommend on Facebook ... the flu is to get vaccinated each year. Flu Vaccination Why should people get vaccinated against the ...

  13. Meningococcal group B vaccines.

    Science.gov (United States)

    Findlow, Jamie

    2013-06-01

    Meningococcal disease remains a devastating and feared infection with a significant morbidity and mortality profile. The successful impact of meningococcal capsular group C glyconconjugate vaccines introduced into the UK infant immunization schedule in 1999, has resulted in >80% of disease now being attributable to meningococcal capsular group B (MenB). MenB glyconconjugate vaccines are not immunogenic and hence, vaccine design has focused on sub-capsular antigens. Recently, a four component vaccine to combat MenB disease (4CMenB) has progressed through clinical development and was approved by the European Medicines Agency at the end of 2012. This vaccine has proven safe and immunogenic and has been predicted to provide protection against ~73% of the MenB disease from England and Wales. Recommendation/implementation of the vaccine into the UK infant schedule is currently being evaluated. 4CMenB has the potential to provide protection against a significant proportion of MenB disease in the UK which is currently unpreventable.

  14. Genome-derived vaccines.

    Science.gov (United States)

    De Groot, Anne S; Rappuoli, Rino

    2004-02-01

    Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

  15. Monitoring the kinetics of the pH-driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance.

    Science.gov (United States)

    Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; McGinn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E P; Pentelute, B L; Collier, R John; Fisher, Mark T

    2013-09-17

    Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å β barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH-dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor, from the endosome to the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance and biolayer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from 7.5 to 5.0, mirroring acidification of the endosome. Once it had undergone the transition, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto electron microscopy grids, where PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early (pH 5.5) or late (pH 5.0) endosomal pH conditions. Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and the soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions.

  16. Monitoring the kinetics of the pH driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance

    Science.gov (United States)

    Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; Mcginn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E. P.; Pentelute, B. L.; Collier, R. John; Fisher, Mark T.

    2013-01-01

    Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å beta barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor (EF), from the endosome into the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance (SPR) and bio-layer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from pH 7.5 to pH 5.0, mirroring acidification of the endosome. Once transitioned, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto EM grids, where the PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early or late endosomal pH conditions (5.5 to 5.0 respectively). Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions. PMID:23964683

  17. Rapid assessment of agents of biological terrorism: defining the differential diagnosis of inhalational anthrax using electronic communication in a practice-based research network.

    Science.gov (United States)

    Temte, Jonathan L; Anderson, Anna Lisa

    2004-01-01

    Early detection of bioterrorism requires assessment of diagnoses assigned to cases of rare diseases with which clinicians have little experience. In this study, we evaluated the process of defining the differential diagnosis for inhalational anthrax using electronic communication within a practice-based research network (PBRN) and compared the results with those obtained from a nationwide random sample of family physicians with a mailed instrument. We distributed survey instruments by e-mail to 55 physician members of the Wisconsin Research Network (WReN), a regional PBRN. The instruments consisted of 3 case vignettes randomly drawn from a set describing 11 patients with inhalational anthrax, 2 with influenza A, and 1 with Legionella pneumonia. Physicians provided their most likely nonanthrax diagnosis, along with their responses to 4 yes-or-no management questions for each case. Physicians who had not responded at 1 week received a second e-mail with the survey instrument. The comparison group consisted of the nationwide sample of physicians who completed mailed survey instruments. Primary outcome measures were response rate, median response time, and frequencies of diagnostic categories assigned to cases of inhalational anthrax. The PBRN response rate compared favorably with that of the national sample (47.3% vs 37.0%; P = not significant). The median response time for the PBRN was significantly shorter than that for the national sample (2 vs 28 days; P < .001). No significant differences were found between the PBRN and the Midwest subset of the national sample in the frequencies of major diagnostic categories or in case management. Electronic means of creating differential diagnoses for rare infectious diseases of national significance is feasible within PBRNs. Information is much more rapidly acquired and is consistent with that obtained by conventional methods.

  18. Transient Co-Expression of Post-Transcriptional Gene Silencing Suppressors for Increased in Planta Expression of a Recombinant Anthrax Receptor Fusion Protein

    Directory of Open Access Journals (Sweden)

    Kittipong Rattanaporn

    2011-08-01

    Full Text Available Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin, CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA domain of human capillary morphogenesis 2 (CMG2, an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG. We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS: p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI, with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI.

  19. Transient co-expression of post-transcriptional gene silencing suppressors for increased in planta expression of a recombinant anthrax receptor fusion protein.

    Science.gov (United States)

    Arzola, Lucas; Chen, Junxing; Rattanaporn, Kittipong; Maclean, James M; McDonald, Karen A

    2011-01-01

    Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA) domain of human capillary morphogenesis 2 (CMG2), an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG). We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS): p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI), with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI.

  20. Microevolution of Anthrax from a Young Ancestor (M.A.Y.A. Suggests a Soil-Borne Life Cycle of Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Peter Braun

    Full Text Available During an anthrax outbreak at the Pollino National Park (Basilicata, Italy in 2004, diseased cattle were buried and from these anthrax-foci Bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. Recent data suggest that B. anthracis multiplies in soil outside the animal-host body. This notion is supported by the frequent isolation of B. anthracis from soil lacking one or both virulence plasmids. Such strains represent an evolutionary dead end, as they are likely no longer able to successfully infect new hosts. This loss of virulence plasmids is explained most simply by postulating a soil-borne life cycle of the pathogen. To test this hypothesis we investigated possible microevolution at two natural anthrax foci from the 2004 outbreak. If valid, then genotypes of strains isolated from near the surface at these foci should be on a different evolutionary trajectory from those below residing in deeper-laying horizons close to the carcass. Thus, the genetic diversity of B. anthracis isolates was compared conducting Progressive Hierarchical Resolving Assays using Nucleic Acids (PHRANA and next generation Whole Genome Sequencing (WGS. PHRANA was not discriminatory enough to resolve the fine genetic relationships between the isolates. Conversely, WGS of nine isolates from near-surface and nine from near-carcass revealed five isolate specific SNPs, four of which were found only in different near-surface isolates. In support of our hypothesis, one surface-isolate lacked plasmid pXO1 and also harbored one of the unique SNPs. Taken together, our results suggest a limited soil-borne life cycle of B. anthracis.

  1. Dual lanthanide-doped complexes: the development of a time-resolved ratiometric fluorescent probe for anthrax biomarker and a paper-based visual sensor.

    Science.gov (United States)

    Wang, Qi-Xian; Xue, Shi-Fan; Chen, Zi-Han; Ma, Shi-Hui; Zhang, Shengqiang; Shi, Guoyue; Zhang, Min

    2017-08-15

    In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO 2 -Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO 2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement. More significantly, a paper-based visual sensor for DPA has been devised by using filter paper embedded with Tb/DPA@SiO 2 -Eu/GMP, and we have proved its utility for fluorescent detection of DPA, in which only a handheld UV lamp is used. In the presence of DPA, the paper-based visual sensor, illuminated by a handheld UV lamp, would result in an obvious fluorescence color change from green to red, which can be easily observed with naked eyes. The paper-based visual sensor is stable, portable, disposable, cost-effective and easy-to-use. The feasibility of using a smartphone with easy-to-access color-scanning APP as the detection platform for quantitative scanometric assays has been also demonstrated by coupled with our proposed paper-based visual sensor. This work unveils an effective method for accurate, sensitive and selective monitoring anthrax biomarker with backgroud-free and self-calibrating properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. How influenza vaccination policy may affect vaccine logistics.

    Science.gov (United States)

    Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T; Welling, Joel S; Norman, Bryan A; Connor, Diana L; Chen, Sheng-I; Slayton, Rachel B; Laosiritaworn, Yongjua; Wateska, Angela R; Wisniewski, Stephen R; Lee, Bruce Y

    2012-06-22

    When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. We Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand. A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time-frame from 1 to 6 months decreases these bottlenecks. Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Glycoconjugate Vaccines: The Regulatory Framework.

    Science.gov (United States)

    Jones, Christopher

    2015-01-01

    Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

  4. Vaccination Perceptions of College Students: With and without Vaccination Waiver

    Directory of Open Access Journals (Sweden)

    Emmanuel D. Jadhav

    2018-02-01

    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.

  5. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. A Dual Role for the Bacillus anthracis Master Virulence Regulator AtxA: Control of Sporulation and Anthrax Toxin Production.

    Science.gov (United States)

    Dale, Jennifer L; Raynor, Malik J; Ty, Maureen C; Hadjifrangiskou, Maria; Koehler, Theresa M

    2018-01-01

    Bacillus anthracis is an endemic soil bacterium that exhibits two different lifestyles. In the soil environment, B. anthracis undergoes a cycle of saprophytic growth, sporulation, and germination. In mammalian hosts, the pathogenic lifestyle of B. anthracis is spore germination followed by vegetative cell replication, but cells do not sporulate. During infection, and in specific culture conditions, transcription of the structural genes for the anthrax toxin proteins and the biosynthetic operon for capsule synthesis is positively controlled by the regulatory protein AtxA. A critical role for the atxA gene in B. anthracis virulence has been established. Here we report an inverse relationship between toxin production and sporulation that is linked to AtxA levels. During culture in conditions favoring sporulation, B. anthracis produces little to no AtxA. When B. anthracis is cultured in conditions favoring toxin gene expression, AtxA is expressed at relatively high levels and sporulation rate and efficiency are reduced. We found that a mutation within the atxA promoter region resulting in AtxA over-expression leads to a marked sporulation defect. The sporulation phenotype of the mutant is dependent upon pXO2-0075 , an atxA -regulated open reading frame located on virulence plasmid pXO2. The predicted amino acid sequence of the pXO2-0075 protein has similarity to the sensor domain of sporulation sensor histidine kinases. It was shown previously that pXO2-0075 overexpression suppresses sporulation. We have designated pXO2-0075 " skiA " for "sporulation kinase inhibitor." Our results indicate that in addition to serving as a positive regulator of virulence gene expression, AtxA modulates B. anthracis development.

  7. Anthrax lethal toxin inhibits translation of hypoxia-inducible factor 1α and causes decreased tolerance to hypoxic stress.

    Science.gov (United States)

    Ouyang, Weiming; Torigoe, Chikako; Fang, Hui; Xie, Tao; Frucht, David M

    2014-02-14

    Hypoxia is considered to be a contributor to the pathology associated with administration of anthrax lethal toxin (LT). However, we report here that serum lactate levels in LT-treated mice are reduced, a finding inconsistent with the anaerobic metabolism expected to occur during hypoxia. Reduced lactate levels are also observed in the culture supernatants of LT-treated cells. LT inhibits the accumulation of hypoxia-inducible factor (HIF)-1α, a subunit of HIF-1, the master regulator directing cellular responses to hypoxia. The toxin has no effect on the transcription or protein turnover of HIF-1α, but instead it acts to inhibit HIF-1α translation. LT treatment diminishes phosphorylation of eIF4B, eIF4E, and rpS6, critical components of the intracellular machinery required for HIF-1α translation. Moreover, blockade of MKK1/2-ERK1/2, but not p38 or JNK signaling, lowers HIF-1α protein levels in both normoxic and hypoxic conditions, consistent with a role for MKK1 and MKK2 as the major targets of LT responsible for the inhibition of HIF-1α translation. The physiological importance of the LT-induced translation blockade is demonstrated by the finding that LT treatment decreases the survival of hepatocyte cell lines grown in hypoxic conditions, an effect that is overcome by preinduction of HIF-1α. Taken together, these data support a role for LT in dysregulating HIF-1α and thereby disrupting homeostatic responses to hypoxia, an environmental characteristic of certain tissues at baseline and/or during disseminated infection with Bacillus anthracis.

  8. Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor.

    Directory of Open Access Journals (Sweden)

    Joseph Chavarría-Smith

    Full Text Available Inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the Caspase-1 (CASP1 protease. Activated CASP1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. Inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (NLR or AIM2-like receptor (ALR protein families. Certain NLRs and ALRs have been shown to function as direct receptors for specific microbial ligands, such as flagellin or DNA, but the molecular mechanism responsible for activation of most NLRs is still poorly understood. Here we determine the mechanism of activation of the NLRP1B inflammasome in mice. NLRP1B, and its ortholog in rats, is activated by the lethal factor (LF protease that is a key virulence factor secreted by Bacillus anthracis, the causative agent of anthrax. LF was recently shown to cleave mouse and rat NLRP1 directly. However, it is unclear if cleavage is sufficient for NLRP1 activation. Indeed, other LF-induced cellular events have been suggested to play a role in NLRP1B activation. Surprisingly, we show that direct cleavage of NLRP1B is sufficient to induce inflammasome activation in the absence of LF. Our results therefore rule out the need for other LF-dependent cellular effects in activation of NLRP1B. We therefore propose that NLRP1 functions primarily as a sensor of protease activity and thus could conceivably detect a broader spectrum of pathogens than just B. anthracis. By adding proteolytic cleavage to the previously established ligand-receptor mechanism of NLR activation, our results illustrate the remarkable flexibility with which the NLR architecture can be deployed for the purpose of pathogen-detection and host defense.

  9. Molecular epidemiology of anthrax cases associated with recreational use of animal hides and yarn in the United States.

    Directory of Open Access Journals (Sweden)

    Chung K Marston

    Full Text Available To determine potential links between the clinical isolate to animal products and their geographic origin, we genotyped (MLVA-8, MVLA-15, and canSNP analysis 80 environmental and 12 clinical isolates and 2 clinical specimens from five cases of anthrax (California in 1976 [n = 1], New York in 2006 [n = 1], Connecticut in 2007 [n = 2], and New Hampshire in 2009[n = 1] resulting from recreational handling of animal products. For the California case, four clinical isolates were identified as MLVA-8 genotype (GT 76 and in the canSNP A.Br.Vollum lineage, which is consistent with the Pakistani origin of the yarn. Twenty eight of the California isolates were in the A.Br.Vollum canSNP lineage and one isolate was in the A.Br. 003/004 canSNP sub-group. All 52 isolates and both clinical specimens related to the New York and Connecticut cases were MLVA-8 GT 1. The animal products associated with the NY and CT cases were believed to originate from West Africa, but no isolates from this region are available to be genotyped for comparison. All isolates associated with the New Hampshire case were identical and had a new genotype (GT 149. Isolates from the NY, CT and NH cases diverge from the established canSNP phylogeny near the base of the A.Br.011/009. This report illustrates the power of the current genotyping methods and the dramatically different epidemiological conditions that can lead to infections (i.e., contamination by a single genotype versus widespread contamination of numerous genotypes. These cases illustrate the need to acquire and genotype global isolates so that accurate assignments can be made about isolate origins.

  10. Community vaccine perceptions and its role on vaccination uptake ...

    African Journals Online (AJOL)

    Introduction: Underutilization of vaccines still remains a challenge in many regions across the world. Ileje district is one of the districts in Tanzania with consistently low pentavalent vaccine uptake (69%) and with drop out of 15%. We determined the vaccination completion with regard to Oral Polio virus, Measles, Bacillus ...

  11. Evaluation of vaccine competition using HVT vector vaccines

    Science.gov (United States)

    Turkey herpesvirus (HVT) has been widely used as a vaccine for Marek’s disease (MD) since the 1970s. Because HVT is a safe vaccine that is poorly sensitive to interference from maternally derived antibodies, it has seen rising use as a vector for vaccines developed for protection against other comm...

  12. Flu Vaccine Safety and Pregnancy

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety and Pregnancy Questions & Answers Language: English ( ... flu vaccine? Why should pregnant women get a flu shot? Flu is more likely to cause severe ...

  13. New Vaccines Help Protect You

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues New Vaccines Help Protect You Past Issues / Fall 2006 Table of ... with a few deaths. Therefore, this vaccine will help reduce one of our most common and potentially ...

  14. Macromolecular systems for vaccine delivery.

    Science.gov (United States)

    MuŽíková, G; Laga, R

    2016-10-20

    Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

  15. Liver Disease and Adult Vaccination

    Science.gov (United States)

    ... The Basics Adult Vaccination Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet ... critical for people with health conditions such as liver disease. If you have chronic liver disease, talk ...

  16. HPV Vaccine - Questions and Answers

    Science.gov (United States)

    ... United States currently has the safest, most effective vaccine supply in history. Years of testing are required by law to ensure the safety of vaccines before they are made available for use in ...

  17. HIV-1 vaccines

    Science.gov (United States)

    Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

    2014-01-01

    The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

  18. [Vaccination against rubella].

    Science.gov (United States)

    Rossolini, A; Barberi, A

    1984-01-01

    The infection caused by the rubella virus is a mild disease usually with no or rare complications in children and adults. On the contrary, intrauterine fetal infection may result in defects of the child, which may either be present at birth or become apparent later in life. Such a risk led to the preparation and use of active immunoprophylaxis against rubella in females of child-bearing age, in order to prevent congenital rubella. Three rubella viruses are employed to prepare the vaccine, all derived from the same viral strain. Doubts however, exist about vaccination, in particular about (1) its teratogenic potential in pregnancy; (2) the duration of protection. As a matter of fact, congenital malformations in the fetus exposed to vaccine virus through the mother have been reported in 3% of cases. As to the second point, the data on the protective immunity in time of the vaccine are very controversial. It is clear, anyhow, that protection against infection is associated not only with persistence of adequate serum levels of antibody, but also with other immunological parameters which are still unknown. These considerations, together with the observation that a relative high percentage of vaccine recipients do not respond, lead us to suggest modifications in the present scheduling of immunization against rubella.

  19. Economics of vaccines revisited.

    Science.gov (United States)

    Postma, Maarten J; Standaert, Baudouin A

    2013-05-01

    Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct and indirect) to be measured in a population when using a cohort model; (1) appropriate rules about discounting the long-term impact of vaccines are absent jeopardizing therefore their value at the initial investment; (2) the presence of opposite contexts when introducing the vaccine in developed vs. the developing world with high benefits, low initial health care investment for the latter vs. marginal benefit and high cost for the former; with a corresponding paradox for the vaccine becoming very cost-effective in low income countries but rather medium in middle low to high middle income countries; (3) and the type of trial assessment for the newer vaccines is now often performed with immunogenicity reaction instead of clinical endpoints which still leaves questions on their real impact and their head-to-head comparison. (4.)

  20. Vaccines for the elderly.

    Science.gov (United States)

    Del Giudice, Giuseppe; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

    2015-01-01

    The aging of the human population is posing serious challenges to research and to public health authorities in order to prevent diseases that more frequently affect the elderly, a portion of the population that will increase more and more in the coming years. While some vaccines exist and are used in the elderly to effectively fight against some infections (e.g. influenza, pneumococci, varicella-zoster virus, diphtheria, and tetanus), still a lot of work remains to be done to better adapt these vaccines and to develop new ones for this age group. The prevention of infectious diseases affecting the elderly can be successful only through a holistic approach. This approach will aim at the following: (1) a deeper understanding of the mechanisms leading to the senescence of the immune system, (2) a better and broader use of vaccines recommended for the elderly, (3) the use of vaccines currently considered only for other age groups and (4) actively priming the population when they are immunological competent, before the physiological waning of immune responsiveness may affect the beneficial effects of vaccination. © 2014 S. Karger AG, Basel

  1. Vaccination against tuberculosis.

    Science.gov (United States)

    Martin, Carlos; Aguilo, Nacho; Gonzalo-Asensio, Jesús

    2018-04-04

    BCG (Bacille Calmette-Guérin) vaccination is included in the immunization schedule for tuberculosis endemic countries with a global coverage at birth close to 90% worldwide. BCG was attenuated from Mycobacterium bovis almost a century ago, and provides a strong protection against disseminated forms of the disease, though very limited against pulmonary forms of tuberculosis, responsible for transmission. Novel prophylactic tuberculosis vaccines are in clinical development either to replace BCG or to improve its protection against respiratory forms of the disease. There are limitations understanding the immunological responses involved and the precise type of long-lived immunity that new vaccines need to induce. MTBVAC is the first and only tuberculosis vaccine candidate based on live-attenuated Mycobacterium tuberculosis in clinical evaluation. MTBVAC clinical development plans to target tuberculosis prevention in newborns, as a BCG replacement strategy, and as secondary objective to be tested in adolescents and adults previous vaccinated with BCG. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. Vaccination against seasonal influenza

    CERN Multimedia

    GS Department

    2010-01-01

    This year, as usual, the Medical Service is helping to promote vaccination against seasonal influenza. Vaccination against seasonal flu is especially recommended for anyone who suffers from chronic pulmonary, cardio-vascular or kidney disease or diabetes, is recovering from a serious illness or major surgery, or is over 65 years of age. The flu virus is transmitted through the air and through contact with contaminated surfaces, so frequent hand-washing with soap and/or an antiseptic hand wash is of great importance. As soon as the first symptoms appear (fever above 38°, shivering, coughing, muscle and/or joint pains, generalised weakness), you are strongly recommended to stay at home to avoid spreading the virus. Anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor), with their dose of vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement through UNIQA...

  3. A brief history of vaccines & vaccination in India

    Directory of Open Access Journals (Sweden)

    Chandrakant Lahariya

    2014-01-01

    Full Text Available The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI (1978 and then Universal Immunization Programme (UIP (1985 were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

  4. A brief history of vaccines & vaccination in India.

    Science.gov (United States)

    Lahariya, Chandrakant

    2014-04-01

    The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

  5. Bursitis efter vaccination i skulderregionen

    DEFF Research Database (Denmark)

    Bliddal, Henning; Torp-Pedersen, Søren; Falk-Riecke, Birgit

    2017-01-01

    Shoulder pain may develop after vaccination in the deltoid area due to inadvertent injection of the vaccine into the subdeltoid bursa, which may be located close to the skin. As far as we know, such vaccination reactions occur more frequently than officially registered, and doctors may not be awa...

  6. Protein carriers of conjugate vaccines

    Science.gov (United States)

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  7. Vaccination recommended for pregnant women

    Directory of Open Access Journals (Sweden)

    Justyna Magdalena Skolarczyk

    2017-04-01

    Full Text Available A vaccine is a formulation of biological origin that contains substances capable of inducing immune processes without the ability to cause a disease. Vaccination is considered the best mean to prevent infectious diseases and their serious complications. Vaccination of a pregnant women can provide protection against severe infectious diseases of both pregnant women and their children. The aim of the study is to present currently available types of vaccines recommended for pregnant women and indications for their use by analyzing the data available in the PubMed, and Medline electronic databases. In the United States, vaccination recommendations for pregnant women include inactivated influenza vaccine and tetanus and diphtheria toxoid vaccine (Tdap. In some countries, pregnant women also receive a vaccine against hepatitis B as well as anti hepatitis A and E. There are also studies on vaccines against the RSV virus and pneumococci. Vaccination is the most effective form of prevention of infectious diseases and their use during pregnancy does not entail any additional risk to the mother or her baby. The benefits of vaccination are huge, so pregnant women should take  recommended vaccination and shouldn’t  be afraid of using them.

  8. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

    Science.gov (United States)

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

    2015-05-01

    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species. © 2014 Society for Risk Analysis.

  9. Early life vaccination

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

    2016-01-01

    Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

  10. Vaccination against seasonal influenza

    CERN Multimedia

    DG Unit

    2009-01-01

    As every year, the Medical Service is taking part in the campaign to promote vaccination against seasonal influenza. Vaccination against seasonal influenza is especially recommended for people suffering from chronic lung, cardio-vascular or kidney conditions or diabetes, for those recovering from a serious illness or surgical operation and for everyone over the age of 65. The influenza virus is transmitted by air and contact with contaminated surfaces, hence the importance of washing hands regularly with soap and / or disinfection using a hydro-alcoholic solution. From the onset of symptoms (fever> 38°, chills, cough, muscle aches and / or joint pain, fatigue) you are strongly recommended to stay at home to avoid spreading the virus. In the present context of the influenza A (H1N1) pandemic, it is important to dissociate these two illnesses and emphasise that the two viruses and the vaccines used to combat them are quite different and that protection against one will not pr...

  11. Meningococcal B vaccine. An immunogenic vaccine possibly useful during outbreaks.

    Science.gov (United States)

    2014-09-01

    Invasive meningococcal infections can be life-threatening and cause severe sequelae. Antibiotic therapy is only partially effective. Bexsero is the first meningococcal B vaccine to be approved in the European Union. It contains four capsular antigens from various strains of group B meningococci. Clinical trials of this meningococcal B vaccine did not assess clinical protection. Two immunogenicity studies in adults, one in adolescents and six in infants, are available. They established the immunogenicity of the meningococcal B vaccine, determined age-appropriate vaccination schedules, and verified that concomitant administration of other vaccines did not undermine its immunogenicity. In the absence of relevant clinical trials, an in vitro study showed that sera from vaccinated individuals were likely to have bactericidal activity against 85% of 200 invasive meningococcal B strains isolated in France in 2007-2008. The meningococcal B vaccine provoked local adverse effects in most vaccinees, including local erythema, induration and pain. Fever occurred in about half of vaccinated children. Six cases of Kawasaki syndrome have been reported in children who received the vaccine, compared to only one case in control groups. In practice, the harm-benefit balance of this meningococcal B vaccine justify using it during outbreaks, provided the outbreak strain is covered by the vaccine antigens. Vaccinees should be enrolled in studies designed to evaluate clinical efficacy and to better determine the risk of Kawasaki syndrome.

  12. Vaccines for Canine Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Faeze Foroughi-Parvar

    2014-01-01

    Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.

  13. [From new vaccine to new target: revisiting influenza vaccination].

    Science.gov (United States)

    Gérard, M

    2011-09-01

    Annual vaccination is since many years the corner stone of Influenza control strategy. Because conventional vaccine are needle-based, are less immunogenic in old people and induce only systemic IgG production, intranasal and intradermal vaccines that are recently or will be soon available in Belgium will offer distinct advantages. Intradermal vaccination is on the Belgian market since 2010. A stronger immune response that allows an antigen sparing strategy is elicited because antigens are delivered near the dermal dendritic cells. Local side effects are more pronounced than after intramuscular injection. The needle-free intranasal vaccine that has been approved for use in people less than 18 years old by the EMEA in October 2010 induces also a mucosal IgA response. Improved clinical results than with intramuscular vaccine has been documented in several studies in children. Several conditions are contraindication to nasal vaccination because of patterns of side effects and because the vaccine is an live-attenuated vaccine. Pregnant women has become a top priority for Influenza vaccination in the recommendations of the High Council of Health in Belgium since the 2009 H1N1 pandemic. Several studies has since then documented the increased risk for Influenza-related morbidity in pregnant women especially during the third trimester and independently of the presence of other comorbidities. Reduced incidence of documented Influenza and of Influenza-related hospitalizations are observed in the new born of vaccinated women until 6 months of age. Availability of new vaccines for Influenza and better knowledge of the benefit of vaccination in target populations are important tools to optimize vaccine coverage of the population.

  14. Noninvasive vaccination against infectious diseases.

    Science.gov (United States)

    Zheng, Zhichao; Diaz-Arévalo, Diana; Guan, Hongbing; Zeng, Mingtao

    2018-04-06

    The development of a successful vaccine, which should elicit a combination of humoral and cellular responses to control or prevent infections, is the first step in protecting against infectious diseases. A vaccine may protect against bacterial, fungal, parasitic, or viral infections in animal models, but to be effective in humans there are some issues that should be considered, such as the adjuvant, the route of vaccination, and the antigen-carrier system. While almost all licensed vaccines are injected such that inoculation is by far the most commonly used method, injection has several potential disadvantages, including pain, cross contamination, needlestick injury, under- or overdosing, and increased cost. It is also problematic for patients from rural areas of developing countries, who must travel to a hospital for vaccine administration. Noninvasive immunizations, including oral, intranasal, and transcutaneous administration of vaccines, can reduce or eliminate pain, reduce the cost of vaccinations, and increase their safety. Several preclinical and clinical studies as well as experience with licensed vaccines have demonstrated that noninvasive vaccine immunization activates cellular and humoral immunity, which protect against pathogen infections. Here we review the development of noninvasive immunization with vaccines based on live attenuated virus, recombinant adenovirus, inactivated virus, viral subunits, virus-like particles, DNA, RNA, and antigen expression in rice in preclinical and clinical studies. We predict that noninvasive vaccine administration will be more widely applied in the clinic in the near future.

  15. A defense of compulsory vaccination.

    Science.gov (United States)

    Flanigan, Jessica

    2014-03-01

    Vaccine refusal harms and risks harming innocent bystanders. People are not entitled to harm innocents or to impose deadly risks on others, so in these cases there is nothing to be said for the right to refuse vaccination. Compulsory vaccination is therefore justified because non-vaccination can rightly be prohibited, just as other kinds of harmful and risky conduct are rightly prohibited. I develop an analogy to random gunfire to illustrate this point. Vaccine refusal, I argue, is morally similar to firing a weapon into the air and endangering innocent bystanders. By re-framing vaccine refusal as harmful and reckless conduct my aim is to shift the focus of the vaccine debate from non-vaccinators' religious and refusal rights to everyone else's rights against being infected with contagious illnesses. Religious freedom and rights of informed consent do not entitle non-vaccinators to harm innocent bystanders, and so coercive vaccination requirements are permissible for the sake of the potential victims of the anti-vaccine movement.

  16. Veterinary and human vaccine evaluation methods

    Science.gov (United States)

    Knight-Jones, T. J. D.; Edmond, K.; Gubbins, S.; Paton, D. J.

    2014-01-01

    Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines. PMID:24741009

  17. Vaccines for preventing Japanese encephalitis

    DEFF Research Database (Denmark)

    Schiøler, Karin Linda; Samuel, Miny; Wai, Kim Lay

    2007-01-01

    BACKGROUND: Vaccination is recognized as the only practical measure for preventing Japanese encephalitis. Production shortage, costs, and issues of licensure impair vaccination programmes in many affected countries. Concerns over vaccine effectiveness and safety also have a negative impact...... on acceptance and uptake. OBJECTIVES: To evaluate vaccines for preventing Japanese encephalitis in terms of effectiveness, adverse events, and immunogenicity. SEARCH STRATEGY: In March 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 1......), MEDLINE, EMBASE, LILACS, BIOSIS, and reference lists. We also attempted to contact corresponding authors and vaccine companies. SELECTION CRITERIA: Randomized controlled trials (RCTs), including cluster-RCTs, comparing Japanese encephalitis vaccines with placebo (inert agent or unrelated vaccine...

  18. The varicella zoster vaccine

    African Journals Online (AJOL)

    Repro

    days. In patients who have received vari- cella zoster immunoglobulin (VZIG), the incubation period is ... his time working on. HIV-related .... The VZV vaccine results in long- lasting immunity ... Studies from Japan show protec- tion for 20 years ...

  19. Economics of vaccines revisited

    NARCIS (Netherlands)

    Postma, Maarten J.; Standaert, Baudouin A.

    2013-01-01

    Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct

  20. Vaccines Help Protect Us

    Centers for Disease Control (CDC) Podcasts

    2013-04-23

    In this podcast for kids, the Kidtastics talk about the importance of vaccines and how they work.  Created: 4/23/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/23/2013.

  1. Advances in influenza vaccination

    NARCIS (Netherlands)

    L.A. Reperant (Leslie); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2014-01-01

    textabstractInfluenza virus infections yearly cause high morbidity and mortality burdens in humans, and the development of a new influenza pandemic continues to threaten mankind as a Damoclean sword. Influenza vaccines have been produced by using egg-based virus growth and passaging techniques that

  2. Immunology of BVDV vaccines

    Science.gov (United States)

    The use of vaccination to control bovine viral diarrhea virus (BVDV) infections presents exceptional challenges due to the nature of the virus, the unique interaction of the virus with the immune system, and its ability to establish persistent infections. The lack of proof reading function during th...

  3. Recombinant Breast Cancer Vaccines

    National Research Council Canada - National Science Library

    Pilon, Shari

    1999-01-01

    .... To generate cytosolic proteins, (cytE2, cytE2A), the ER signal sequence was deleted. Vaccination of BALB/c mice with DNA encoding transmembrane E2 or E2A induced anti-ErbB-2 antibodies and anti-tumor immunity, with E2 being more potent than E2A...

  4. Vaccines and multiple sclerosis

    DEFF Research Database (Denmark)

    Frederiksen, J. L.; Topsøe Mailand, M.

    2017-01-01

    An association between certain vaccinations and onset or relapse of multiple sclerosis (MS) has been debated. Based on PubMed, we made a thorough literature review and included all relevant studies, 51 on MS and 15 on optic neuritis (ON). Case studies were excluded. With the exception of a live...

  5. Vaccines and multiple sclerosis

    DEFF Research Database (Denmark)

    Mailand, Mia Topsøe; Frederiksen, Jette Lautrup

    2017-01-01

    on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...

  6. Tetanus, Diphtheria (Td) Vaccine

    Science.gov (United States)

    Decavac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They ... United States today, but people who do become infected often have severe ...

  7. Genetically modified tumour vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2005-01-01

    Roč. 3, Suppl. 1 (2005), S7 ISSN 1214-021X. [Cells VI - Biological Days /18./. 24.10.2005-26.10.2005, České Budějovice] Institutional research plan: CEZ:AV0Z50520514 Keywords : tumour vaccines * HPV16 Subject RIV: EC - Immunology

  8. HPV Vaccine PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.)

  9. Nanotechnology and vaccine development

    Directory of Open Access Journals (Sweden)

    Mi-Gyeong Kim

    2014-10-01

    Full Text Available Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrier-based vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needle-free nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

  10. ADULT INFLUENZA VACCINATION GUIDELINE

    African Journals Online (AJOL)

    Infections with the influenza virus and Streptococcus pneumoniae are associated with ... .well as the potential benefit and the safety of the vaccine ..... 4.6 Antiviral agents for influenza A2 ... persons who are to travel to other areas, e.g. northern.

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

    Directory of Open Access Journals (Sweden)

    Saranya Sridhar

    2015-04-01

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

  12. Brucellosis Vaccines: An Overview

    Directory of Open Access Journals (Sweden)

    Hasanjani-Roushan Mohammad Reza

    2014-10-01

    Full Text Available Objective: Brucellosis is considered as an important zoonotic and worldwide infection with more than half of million human cases, which it occurs more and more in animals like as wild and live stocks. Sheep, cattle, and goats are animal samples that listed. Symptoms of this disease in human are consisted of: undulant fever, back pains, faint, spondylitis, arthritis and orchitis. This infection causes abortion in livestock, and this point is one of the important economic losses. Reduction in milk production is another problem in this disease too. Materials and Methods: This study is conducted by reviewing of the literatures, which are related to this concern, and also visiting PubMed, ISI and other websites. Results: We must pay heed that most zoonoses are maintained in the animal reservoir. These diseases, such as leptospirosis, Q-fever, brucellosis etc. which among them brucellosis can transfer to human via close contact with infected animals or consumption of unpasteurized dairy. Therefore, eradication of this infection in human population is depended on omission of that in possible methods among animals reservoir. Such methods are like test-slaughter and vaccination of livestock. Hence, vaccination is not alone method for controlling, but it is probably economic one. Conclusion: Nowadays a vaccine which is effective for this disease control in human is not available. Of course presented some different vaccines for this infection in livestock that cleave live attenuated, killed bacteria and sub unit. Therefore, for eradication of this disease some vaccines with more effectiveness protection mid fewer side effects are necessary.

  13. Misconceptions about Seasonal Flu and Flu Vaccines

    Science.gov (United States)

    ... Vaccine (LAIV) Misconceptions about Flu Vaccines Vaccine Supply & Distribution Vaccine Supply for 2017-2018 Season Frequently Asked ... conditions. Flu vaccination has been associated with lower rates of some cardiac ... a baby after birth from flu. (Mom passes antibodies onto the developing ...

  14. Current status of flavivirus vaccines.

    Science.gov (United States)

    Barrett, A D

    2001-12-01

    Although there are approximately 68 flaviviruses recognized, vaccines have been developed to control very few human flavivirus diseases. Licensed live attenuated vaccines have been developed for yellow fever (strain 17D) and Japanese encephalitis (strain SA14-14-2) viruses, and inactivated vaccines have been developed for Japanese encephalitis and tick-borne encephalitis viruses. The yellow fever live attenuated 17D vaccine is one of the most efficacious and safe vaccines developed to date and has been used to immunize more than 300 million people. A number of experimental vaccines are being developed, most notably for dengue. Candidate tetravalent live attenuated dengue vaccines are undergoing clinical trials. Other vaccines are being developed using reverse genetics, DNA vaccines, and recombinant immunogens. In addition, the yellow fever 17D vaccine has been used as a backbone to generate chimeric viruses containing the premembrane and envelope protein genes from other flaviviruses. The "Chimerivax" platform has been used to construct chimeric Japanese encephalitis and dengue viruses that are in different phases of development. Similar strategies are being used by other laboratories.

  15. Buccal and sublingual vaccine delivery.

    Science.gov (United States)

    Kraan, Heleen; Vrieling, Hilde; Czerkinsky, Cecil; Jiskoot, Wim; Kersten, Gideon; Amorij, Jean-Pierre

    2014-09-28

    Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms to prevent the immune system from overreacting to the many environmental antigens. Hence, mucosal vaccination may suppress the immune system instead of induce a protective immune response. Therefore, mucosal adjuvants and/or special antigen delivery systems as well as appropriate dosage forms are required in order to develop potent mucosal vaccines. Whereas oral, nasal and pulmonary vaccine delivery strategies have been described extensively, the sublingual and buccal routes have received considerably less attention. In this review, the characteristics of and approaches for sublingual and buccal vaccine delivery are described and compared with other mucosal vaccine delivery sites. We discuss recent progress and highlight promising developments in the search for vaccine formulations, including adjuvants and suitable dosage forms, which are likely critical for designing a successful sublingual or buccal vaccine. Finally, we outline the challenges, hurdles to overcome and formulation issues relevant for sublingual or buccal vaccine delivery. Copyright © 2014. Published by Elsevier B.V.

  16. Vaccines, inspiring innovation in health.

    Science.gov (United States)

    Pagliusi, Sonia; Dennehy, Maureen; Kim, Hun

    2018-05-19

    This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers' Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of

  17. Vaccine-preventable diseases and vaccination rates in South Dakota.

    Science.gov (United States)

    Kightlinger, Lon

    2013-01-01

    Vaccine-preventable diseases have historically caused much illness and death in South Dakota. Sixty-seven diphtheria deaths were reported in 1892 and 1,017 polio cases were reported at the peak of the polio epidemic in 1952. As vaccines have been developed, licensed and put into wide use, the rates of diphtheria, polio, measles, smallpox and other diseases have successfully decreased leading to control, statewide elimination or eradication. Other diseases, such as pertussis, have been more difficult to control by vaccination alone. Although current vaccination coverage rates for South Dakota's kindergarten children surpass the Healthy People 2020 targets of 95 percent, the coverage rates for 2-year-old children and teenagers are below the target rates. Until vaccine-preventable diseases are eradicated globally, we must vigilantly maintain high vaccination coverage rates and aggressively apply control measures to limit transmission when diseases do occur in South Dakota.

  18. DNA vaccines for aquacultured fish

    DEFF Research Database (Denmark)

    Lorenzen, Niels; LaPatra, S.E.

    2005-01-01

    of licensing and public acceptance of the technology. The potential benefits of DNA vaccines for farmed fish include improved animal welfare, reduced environmental impacts of aquaculture activities, increased food quality and quantity, and more sustainable production. Testing under commercial production......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...

  19. Vaccine prophylaxis: achievements, problems, perspectives of development

    Directory of Open Access Journals (Sweden)

    Mavrutenkov V.V.

    2016-09-01

    Full Text Available The article presents medical and social aspects of immune prophylaxis of infectious diseases; the history of vaccines and vaccination is presented, as well as perspectives of development of vaccine prophylaxis.

  20. What Vaccinations Does My Child Need?

    Science.gov (United States)

    ... needed before your child can enter school or childcare. How do vaccines work? Vaccines help your child’s ... routine vaccines is covered by your health insurance company. How do I know when my child should ...

  1. HPV Vaccine Information for Young Women

    Science.gov (United States)

    ... Transmitted Diseases (STDs) HPV Vaccine Information For Young Women Language: English Español (Spanish) Recommend on Facebook Tweet ... warts at any point in time. Which girls/women should receive HPV vaccination? HPV vaccination is recommended ...

  2. Sudden Infant Death Syndrome (SIDS) and Vaccines

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  3. Tdap (tetanus, diphtheria, pertussis) Vaccine and Pregnancy

    Science.gov (United States)

    ... Can I receive the Tdap vaccine while breastfeeding? Yes. Noninfectious vaccines like Tdap are compatible with breastfeeding. If you get the vaccine while breastfeeding, it can help prevent you from getting sick and passing the illness to your baby. ...

  4. For Parents: Vaccines for Your Children

    Science.gov (United States)

    ... content Start of Search Controls Search Form Controls Vaccines site Cancel Submit CDC A-Z Index MENU ... Z # Start of Search Controls Search Form Controls Vaccines site Cancel Submit For Parents: Vaccines for Your ...

  5. Meningococcal Vaccines: What You Need to Know

    Science.gov (United States)

    ... Español Text Size Email Print Share Meningococcal ACWY Vaccines: What You Need to Know (VIS) Page Content ... to help protect against serogroup B . Meningococcal ACWY Vaccines There are two kinds of meningococcal vaccines licensed ...

  6. Preventing Cervical Cancer with HPV Vaccines

    Science.gov (United States)

    Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.

  7. Production of biopharmaceuticals and vaccines in plants via the chloroplast genome.

    Science.gov (United States)

    Daniell, Henry

    2006-10-01

    Transgenic plants offer many advantages, including low cost of production (by elimination of fermenters), storage and transportation; heat stability; and absence of human pathogens. When therapeutic proteins are orally delivered, plant cells protect antigens in the stomach through bioencapsulation and eliminate the need for expensive purification and sterile injections, in addition to development of both systemic and mucosal immunity. Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance and multi-gene expression in a single transformation event. Hyper-expression of vaccine antigens against cholera, tetanus, anthrax, plague or canine parvovirus (4-31% of total soluble protein, tsp) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato), as well as the availability of antibiotic-free selectable markers or the ability to excise selectable marker genes, facilitate oral delivery. Hyper-expression of several therapeutic proteins, including human serum albumin (11.1% tsp), somatotropin (7% tsp), interferon-gamma (6% tsp), anti-microbial peptide (21.5% tsp), facilitates efficient and economic purification. Also, the presence of chaperones and enzymes in chloroplasts facilitate assembly of complex multi-subunit proteins and correct folding of human blood proteins with proper disulfide bonds. Functionality of chloroplast-derived vaccine antigens and therapeutic proteins has been demonstrated by several assays, including the macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLa cells or human lung carcinoma cells against encephalomyocarditis virus, systemic immune response, protection against pathogen challenge, and growth or inhibition of cell cultures. Thus, transgenic chloroplasts are ideal bioreactors for production of functional human and animal therapeutic proteins in an environmentally friendly manner.

  8. Yellow Fever Vaccine: What You Need to Know

    Science.gov (United States)

    ... How can I prevent yellow fever? Yellow fever vaccine Yellow fever vaccine can prevent yellow fever. Yellow fever vaccine ... such as those containing DEET. 3 Yellow fever vaccine Yellow fever vaccine is a live, weakened virus. It is ...

  9. Rotavirus and the Vaccine (Drops) to Prevent It

    Science.gov (United States)

    ... Resources Maternal Immunization Resources Related Links Vaccines & Immunizations Rotavirus and the Vaccine (Drops) to Prevent It Language: ... the vaccine. Why should my child get the rotavirus vaccine? The rotavirus vaccine: Protects your child from ...

  10. Vaccines for preventing typhoid fever.

    Science.gov (United States)

    Milligan, Rachael; Paul, Mical; Richardson, Marty; Neuberger, Ami

    2018-05-31

    Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages. To assess the effects of vaccines for preventing typhoid fever. In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible. Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses

  11. Dendritic cell vaccines.

    Science.gov (United States)

    Mosca, Paul J; Lyerly, H Kim; Clay, Timothy M; Morse, Michael A; Lyerly, H Kim

    2007-05-01

    Dendritic cells are antigen-presenting cells that have been shown to stimulate tumor antigen-specific T cell responses in preclinical studies. Consequently, there has been intense interest in developing dendritic cell based cancer vaccines. A variety of methods for generating dendritic cells, loading them with tumor antigens, and administering them to patients have been described. In recent years, a number of early phase clinical trials have been performed and have demonstrated the safety and feasibility of dendritic cell immunotherapies. A number of these trials have generated valuable preliminary data regarding the clinical and immunologic response to DC-based immunotherapy. The emphasis of dendritic cell immunotherapy research is increasingly shifting toward the development of strategies to increase the potency of dendritic cell vaccine preparations.

  12. Experiements with an inactivated hepatitis leptospirosis vaccine in vaccination programmes for dogs.

    Science.gov (United States)

    Wilson, J H; Hermann-Dekkers, W M; Leemans-Dessy, S; Meijer, J W

    1977-06-25

    A fluid adjuvanted vaccine consisting of inactivated hepatitis virus (iH) and leptospirae antigens (L) was developed. The vaccine (Kavak iHL; Duphar) was tested in several vaccination programmes both alone and in combination with freeze dried measles (M) or distemper (D) vaccines. The results demonstrate that this new vaccine is also effective in pups with maternally derived antibodies, although a second vaccination at 14 weeks of age is recommended to boost the first vaccination. For the booster vaccination either the iHL-vaccine or the liver attenuated hepatitis vaccine (H) can be used.

  13. Vaccines provided by family physicians.

    Science.gov (United States)

    Campos-Outcalt, Doug; Jeffcott-Pera, Michelle; Carter-Smith, Pamela; Schoof, Bellinda K; Young, Herbert F

    2010-01-01

    This study was conducted to document current immunization practices by family physicians. In 2008 the American Academy of Family Physicians (AAFP) conducted a survey among a random sample of 2,000 of its members who reported spending 80% or more of their time in direct patient care. The survey consisted of questions regarding the demographics of the practice, vaccines that are provided at the physicians' clinical site, whether the practice refers patients elsewhere for vaccines, and participation in the Vaccines for Children (VFC) program. The response rate was 38.5%, 31.8% after non-office-based respondents were deleted. A high proportion of respondents (80% or more) reported providing most routinely recommended child, adolescent, and adult vaccines at their practice sites. The exceptions were rotavirus vaccine for children and herpes zoster vaccine for adults., A significant proportion, however, reported referring elsewhere for some vaccines (44.1% for children and adolescent vaccines and 53.5% for adult vaccines), with the most frequent referral location being a public health department. A higher proportion of solo and 2-physician practices than larger practices reported referring patients. A lack of adequate payment was listed as the reason for referring patients elsewhere for vaccines by one-half of those who refer patients. One-half of responders do not participate in the VFC program. Provision of recommended vaccines by most family physicians remains an important service. Smaller practices have more difficulty offering a full array of vaccine products, and lack of adequate payment contributes to referring patients outside the medical home. The reasons behind the lack of participation in the VFC program deserve further study.

  14. Reproductive toxicity testing of vaccines

    International Nuclear Information System (INIS)

    Verdier, Francois; Barrow, Paul C.; Burge, Joeelle

    2003-01-01

    Vaccines play a major role in the prevention of human birth defects by protecting the pregnant woman from teratogenic or otherwise harmful infections. Until now, it has not been common practice to perform preclinical developmental toxicity tests for new vaccines. Despite the excellent safety record of vaccines, increased attention is now being given to the feasibility of screening new vaccines for developmental hazards in animals before their use in humans. Contrary to previous assumptions, many vaccines are now given to potentially pregnant women. Any new components of the vaccine formulation (adjuvants, excipients, stabilisers, preservatives, etc...) could also be tested for influences on development, although based on past experience the risks are limited by the very low dosages used. The conferred immunity following vaccination lasts for several years. Therefore, the developing conceptus may theoretically be exposed to the induced antibodies and/or sensitised T-cells, even if the pregnant woman was last vaccinated during childhood (particularly if she encounters the antigen during pregnancy through exposure to infection). However, it should be kept in mind that viral or bacterial infections represent a higher risk for a pregnant woman than the potential adverse effects related to vaccination or the associated immune response. Non-clinical safety studies may be employed as an aid for hazard identification. In these studies interactions of the vaccine with the maternal immune system or with the developmental systems of the offspring are considered. Post-natal examinations are necessary to detect all possible manifestations of developmental toxicity, such as effects on the immune system. Species selection for the preclinical studies is based on immunogenicity to the vaccine and the relative timing and rate of transfer of maternal antibodies to the offspring. A single study design is proposed for the pre- and post-natal developmental assessments of vaccines in

  15. Molecular Vaccines for Malaria

    Science.gov (United States)

    2010-01-01

    Removing inhibitory plasm ids from the cock- with the radiation-attenuated sporozoite (RAS) vaccine36•37 (see tail restored the immunogenicity of the...relative increased in vitro growth inhibitory activity against homologous to the P. folciparum antigen expressing plasm ids alone, and none parasites...25nm and have a molecular weight of 14.8 kDa. (C) Transmission electron microscopy image of P4c-Mal nanoparticles at 242 OOOx. The sample was

  16. Ebola vaccine and treatment.

    Science.gov (United States)

    Takada, Ayato

    2015-01-01

    Filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever in humans and nonhuman primates. No effective prophylaxis or treatment for filovirus diseases is yet commercially available. The recent outbreak of Ebola virus disease in West Africa has accelerated efforts to develop anti-Ebola virus prophylaxis and treatment, and unapproved drugs were indeed used for the treatment of patients during the outbreak. This article reviews previous researches and the latest topics on vaccine and therapy for Ebola virus disease.

  17. Vaccination against seasonal influenza

    CERN Multimedia

    SC Unit

    2009-01-01

    As every year, the Medical Service is taking part in the campaign to promote vaccination against seasonal influenza. Vaccination against seasonal influenza is especially recommended for people suffering from chronic lung, cardio-vascular or kidney conditions or diabetes, for those recovering from a serious illness or surgical operation and for everyone over the age of 65. The influenza virus is transmitted by air and contact with contaminated surfaces, hence the importance of washing hands regularly with soap and / or disinfection using a hydro-alcoholic solution. From the onset of symptoms (fever> 38°, chills, cough, muscle aches and / or joint pain, fatigue) you are strongly recommended to stay at home to avoid spreading the virus. In the present context of the influenza A (H1N1) pandemic, it is important to dissociate these two illnesses and emphasise that the two viruses and the vaccines used to combat them are quite different and that protection against one will not provide protection against the...

  18. Understanding vaccines: a public imperative.

    Science.gov (United States)

    Federman, Ross S

    2014-12-01

    Though once a discovery greatly celebrated by the nation, the vaccine has come under fire in recent decades from skeptics, critics, and a movement set into motion by fraudulent scientists and fueled by frustrated parents looking for answers to the autism conundrum. There is enough denialist resistance to vaccination to bring upon renewed fear of young children and infants becoming infected with diseases, the threats of which had been functionally eradicated from the United States. In more recent years, the surge in independent online journalism and blogging has invited many to rapidly share their opinions with millions of readers and, importantly, has appeared to open the door for opinion to be portrayed as fact. As a result, many parents are inundated with horror stories of vaccine dangers, all designed to eat away at them emotionally while the medical and scientific communities have mounted their characteristic response by sharing the facts, the data, and all of the reliable peer-reviewed and well-cited research to show that vaccines are safe and effective. It has become clear to me that facts are no match for emotion, but perhaps an understanding behind vaccine methodology will help parents overcome these fears of vaccinating. By helping those who doubt vaccines better understand what vaccines really are and how they work in such an incredibly engineered fashion, we may have a stronger weapon than we realize in battling the emotional arsenal that comes from the fear and skepticism of vaccinating.

  19. Vaccination against group B streptococcus.

    Science.gov (United States)

    Heath, Paul T; Feldman, Robert G

    2005-04-01

    Streptococcus agalactiae (Group B streptococcus) is an important cause of disease in infants, pregnant women, the elderly and in immunosuppressed adults. An effective vaccine is likely to prevent the majority of infant disease (both early and late onset), as well as Group B streptococcus-related stillbirths and prematurity, to avoid the current real and theoretical limitations of intrapartum antibiotic prophylaxis, and to be cost effective. The optimal time to administer such a vaccine would be in the third trimester of pregnancy. The main limitations on the production of a Group B streptococcus vaccine are not technical or scientific, but regulatory and legal. A number of candidates including capsular conjugate vaccines using traditional carrier proteins such as tetanus toxoid and mutant diphtheria toxin CRM197, as well as Group B streptococcus-specific proteins such as C5a peptidase, protein vaccines using one or more Group B streptococcus surface proteins and mucosal vaccines, have the potential to be successful vaccines. The capsular conjugate vaccines using tetanus and CRM197 carrier proteins are the most advanced candidates, having already completed Phase II human studies including use in the target population of pregnant women (tetanus toxoid conjugate), however, no definitive protein conjugates have yet been trialed. However, unless the regulatory environment is changed specifically to allow the development of a Group B streptococcus vaccine, it is unlikely that one will ever reach the market.

  20. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  1. Influenza Vaccinations, Fall 2009: Model School-Located Vaccination Clinics

    Science.gov (United States)

    Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna

    2010-01-01

    The 2009 H1N1 influenza virus presented a major challenge to health departments, schools, and other community partners to effectively vaccinate large numbers of Americans, primarily children. The use of school-located vaccination (SLV) programs to address this challenge led health departments and schools to become creative in developing models for…

  2. Vaccine platform recombinant measles virus.

    Science.gov (United States)

    Mühlebach, Michael D

    2017-10-01

    The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

  3. [History of vaccination: from empiricism towards recombinant vaccines].

    Science.gov (United States)

    Guérin, N

    2007-01-01

    Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.

  4. Private-sector vaccine purchase costs and insurer payments: a disincentive for using combination vaccines?

    Science.gov (United States)

    Clark, Sarah J; Cowan, Anne E; Freed, Gary L

    2011-04-01

    Combination vaccines have been endorsed as a means to decrease the number of injections needed to complete the childhood immunization schedule, yet anecdotal reports suggest that private providers lose money on combination vaccines. The objective of this study was to determine whether practices purchasing combination vaccines had significantly different vaccine costs and reimbursement compared to practices that were not purchasing combination vaccines. Using cross-sectional purchase and insurer payment data collected from a targeted sample of private practices in five US states, we calculated the average total vaccine cost and reimbursement across the childhood immunization schedule. The average vaccine purchase cost across the childhood schedule was significantly higher for practices using a combined vaccine with diphtheria, tetanus, acellular pertussis vaccine, inactivated polio vaccine, and Hepatitis B vaccine (DTaP-IPV-HepB) than for practices using either separate vaccine products or a combined vaccine with Haemophilus influenzae, type b vaccine and Hepatitis B vaccine (Hib-HepB). The average insurer payment for vaccine administration across the childhood schedule was significantly lower for practices using DTaP-IPV-HepB combination vaccine than for practices using separate vaccine products. This study appears to validate anecdotal reports that vaccine purchase costs and insurer payment for combination vaccines can have a negative financial impact for practices that purchase childhood vaccines.

  5. The recent progress in RSV vaccine technology.

    Science.gov (United States)

    Fretzayas, Andrew; Papadopoulou, Anna; Kotzia, Doxa; Moustaki, Maria

    2012-12-01

    The most effective way to control RSV infection would be the development of an expedient and safe vaccine. Subunit vaccines, live attenuated RSV vaccines, plasmid DNA vaccines have been tested either in human or in mouse models without reaching the ultimate goal of efficacy and safety, at least in humans. Viruses such as adenovirus, sendai virus, measles virus were also used as vectors for the generation of RSV vaccines with promising results in animal models. Recent patents describe new techniques for the generation of candidate vaccines. These patents include virus like particles as vaccine platforms, recombinant RSVs or modified RSV F protein as component of the vaccine. Despite the number of the candidate vaccines, the new RSV vaccines should overcome many obstacles before being established as effective vaccines for the control of RSV infections especially for the young infants who are more susceptible to the virus.

  6. Life course vaccination and healthy aging.

    Science.gov (United States)

    Gusmano, Michael K; Michel, Jean-Pierre

    2009-06-01

    The authors notice the low vaccine coverage rate among European citizens and inventory the multiple reasons leading to the non-use of preventable infectious diseases vaccines in adults whose mortality consequences represent an important and unexpected burden of diseases. These facts are in close relation with the disruption of vaccine recommendations after the childhood vaccine program, the poor literacy knowledge concerning vaccines among the general population, but also unfortunately among physicians and other health care workers. Popular beliefs, fear of side-effects, fear of needles facilitated the constitution of active non-vaccine groups which conduct to the reappearance in non-vaccinated adults and with dramatic consequences of preventable childhood infectious diseases. This careful analysis of the current preventable infectious disease vaccine coverage in old adults leads to propose a life course vaccine programme including adult vaccinations as part of healthy aging as well as old adults' vaccine guidelines integrated in health prevention programs.

  7. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    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

  8. Now and future influenza vaccines.

    Science.gov (United States)

    Ruben, F L

    1990-03-01

    Influenza is a modern day plague. In the young, the clinical picture is classical, but in the elderly, the disease may go unsuspected until complications such as pneumonia develop. Influenza A and B viruses are responsible, and these viruses mutate with great regularity. Antibodies to the HA and NA surface antigens of influenza viruses, both naturally and vaccine induced, are protective. The earliest influenza vaccines were crude, toxic, and ineffective. With modern purification techniques, the egg-grown viruses have been turned into safe, immunogenic, and effective killed-virus vaccines--whole virus and split virus. Surveillance permits the correct virus strains to be incorporated into each new vaccine. Those who have been experiencing the worst effects of influenza have been identified. These individuals need to be immunized each year. In the future, live influenza virus vaccines may offer the benefits of ease of administration and longer-lasting protection. Synthetic peptides, genetically engineered antigens, and even nonantigen (anti-idiotype) vaccines are possible, but such vaccines will require adjuvant enhancement. For the present, greater efforts must be made to use existing influenza vaccines.

  9. Progress in Brucella vaccine development

    Science.gov (United States)

    YANG, Xinghong; SKYBERG, Jerod A.; CAO, Ling; CLAPP, Beata; THORNBURG, Theresa; PASCUAL, David W.

    2012-01-01

    Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines. PMID:23730309

  10. Mandatory Vaccination: an Unqualified Defence

    NARCIS (Netherlands)

    Pierik, R.

    The 2015 Disneyland outbreak of measles in the US unequivocally brought to light what had been brewing below the surface for a while: a slow but steady decline in vaccination rates resulting in a rising number of outbreaks. This can be traced back to an increasing public questioning of vaccines by

  11. Vaccines against invasive Salmonella disease

    Science.gov (United States)

    MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

    2014-01-01

    Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

  12. Adolescent Attitudes toward Influenza Vaccination and Vaccine Uptake in a School-Based Influenza Vaccination Intervention: A Mediation Analysis

    Science.gov (United States)

    Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; DiClemente, Ralph J.

    2011-01-01

    Background: School-based vaccination programs may provide an effective strategy to immunize adolescents against influenza. This study examined whether adolescent attitudes toward influenza vaccination mediated the relationship between receipt of a school-based influenza vaccination intervention and vaccine uptake. Methods: Participants were…

  13. Development of improved pertussis vaccine.

    Science.gov (United States)

    Rumbo, Martin; Hozbor, Daniela

    2014-01-01

    Rates of infection with Bordetella pertussis, the gram-negative bacterium that causes the respiratory disease called whooping cough or pertussis, have not abated and 16 million cases with almost 200,000 deaths are estimated by the WHO to have occurred worldwide in 2008. Despite relatively high vaccination rates, the disease has come back in recent years to afflict people in numbers not seen since the pre-vaccine days. Indeed, pertussis is now recognized as a frequent infection not only in newborn and infants but also in adults. The disease symptoms also can be induced by the non-vaccine-preventable infection with the close species B. parapertussis for which an increasing number of cases have been reported. The epidemiologic situation and current knowledge of the limitations of pertussis vaccine point out the need to design improved vaccines. Several alternative approaches and their challenges are summarized.

  14. ERM immersion vaccination and adjuvants

    DEFF Research Database (Denmark)

    Skov, J.; Chettri, J. K.; Jaafar, R. M.

    2015-01-01

    Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

  15. Twenty-first century vaccines

    Science.gov (United States)

    Rappuoli, Rino

    2011-01-01

    In the twentieth century, vaccination has been possibly the greatest revolution in health. Together with hygiene and antibiotics, vaccination led to the elimination of many childhood infectious diseases and contributed to the increase in disability-free life expectancy that in Western societies rose from 50 to 78–85 years (Crimmins, E. M. & Finch, C. E. 2006 Proc. Natl Acad. Sci. USA 103, 498–503; Kirkwood, T. B. 2008 Nat. Med 10, 1177–1185). In the twenty-first century, vaccination will be expected to eliminate the remaining childhood infectious diseases, such as meningococcal meningitis, respiratory syncytial virus, group A streptococcus, and will address the health challenges of this century such as those associated with ageing, antibiotic resistance, emerging infectious diseases and poverty. However, for this to happen, we need to increase the public trust in vaccination so that vaccines can be perceived as the best insurance against most diseases across all ages. PMID:21893537

  16. The vaccination programme in Indonesia.

    Science.gov (United States)

    Sawitri Siregar, E; Darminto; Weaver, J; Bouma, A

    2007-01-01

    The Indonesian response to the outbreak of highly pathogenic avian influenza (HPAI) is being strengthened by increased intersectoral commitment and greater availability of staff and resources. Vaccination against avian influenza has been used widely in large commercial sectors but less so in other sectors. Generally, there has been a reduction in outbreaks and in the impact of HPAI on the commercial industry. Afield trial is described that might provide insight into the efficacy of vaccination on farms in sector 3. Preliminary data suggest that vaccination of layers induces high titres, whereas vaccination of native chickens might be difficult owing to a low response in these breeds. A much greater commitment of management, staff and resources is required before vaccination can become part of a successful sustainable campaign to eradicate HPAI. For success, the commercial poultry industry must become an integral part of the control programme, providing information and having the opportunity to identify or modify the priorities of the control programme.

  17. A New Decade of Vaccines

    LENUS (Irish Health Repository)

    Murphy, JFA

    2011-09-01

    The call for a new decade of vaccines was made in December 2010. The aims are to secure the further discovery, development and delivery of vaccination. The first challenge is the acquisition of funds for the research and development of 20 new vaccines1. The Gates Foundation has pledged $10 billion for this venture. The other major players are WHO, UNICEF and the US National Institute of Allergy and Infectious Diseases. The top priorities are TB, AIDS and Malaria. It is hoped that a Malaria vaccine will available in 3 years. The ambitious target of saving the lives of over 7 million children has been set. The programme must also address the need for vaccines in insulin dependent diabetes, cancers and degenerative diseases2.

  18. Points for Consideration for dengue vaccine introduction - recommendations by the Dengue Vaccine Initiative.

    Science.gov (United States)

    Lim, Jacqueline Kyungah; Lee, Yong-Seok; Wilder-Smith, Annelies; Thiry, Georges; Mahoney, Richard; Yoon, In-Kyu

    2016-01-01

    Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction.

  19. Vaccine strategies against schistosomiasis

    Directory of Open Access Journals (Sweden)

    A. Capron

    1992-01-01

    Full Text Available Schistosomiasis, the second major parasitic disease in the world after malaria affects at least 200 million people, 500 million being exposed to the risk of infection. It is widely agreed that a vaccine strategy wich could lead to the induction of effector mechanisms reducing the level of reinfection and ideally parasite fecundity would deeply affect the incidence of pathological manifestations as well as the parasite transmission potentialities. Extensive studies performed in the rat model have allowed the identification of novel effector mechanisms involving IgE antibodies and various inflammatory cell populations (eosinophils, macrophages and platelets whereas regulation of immune response by blocking antibodies has been evidencial. Recent epidemiological studies have now entirely confirmed in human populations the the role of IgE antibodies in the acquisition of resistance and the association of IgG4 blocking antibodies with increased susceptibility. On the basis of these concepts, several schistosome glutathion S-transferase (Sm 28 GST appears as a pronising vaccine candidate. Immunization experiments have shown that two complementary goals can be achieved: (a a partial but significant reduction of the worm population (up to 60//in rats; (b a significant reduction of parasite fecundity (up in the mice and 85//in cattle and egg viability (up to 80//. At least two distinct immunological mechanisms account for these two effects. IgE antibodies appear as a major humoral component of acquired resistance whereas IgA antibodies appear as a major humoral factor affecting parasite fecundity. These studies seem to represent a parasite diseases through the identification of potentially protective antigens and of the components of the immune response which vaccination should aim at inducing.

  20. Statistical physics of vaccination

    Science.gov (United States)

    Wang, Zhen; Bauch, Chris T.; Bhattacharyya, Samit; d'Onofrio, Alberto; Manfredi, Piero; Perc, Matjaž; Perra, Nicola; Salathé, Marcel; Zhao, Dawei

    2016-12-01

    Historically, infectious diseases caused considerable damage to human societies, and they continue to do so today. To help reduce their impact, mathematical models of disease transmission have been studied to help understand disease dynamics and inform prevention strategies. Vaccination-one of the most important preventive measures of modern times-is of great interest both theoretically and empirically. And in contrast to traditional approaches, recent research increasingly explores the pivotal implications of individual behavior and heterogeneous contact patterns in populations. Our report reviews the developmental arc of theoretical epidemiology with emphasis on vaccination, as it led from classical models assuming homogeneously mixing (mean-field) populations and ignoring human behavior, to recent models that account for behavioral feedback and/or population spatial/social structure. Many of the methods used originated in statistical physics, such as lattice and network models, and their associated analytical frameworks. Similarly, the feedback loop between vaccinating behavior and disease propagation forms a coupled nonlinear system with analogs in physics. We also review the new paradigm of digital epidemiology, wherein sources of digital data such as online social media are mined for high-resolution information on epidemiologically relevant individual behavior. Armed with the tools and concepts of statistical physics, and further assisted by new sources of digital data, models that capture nonlinear interactions between behavior and disease dynamics offer a novel way of modeling real-world phenomena, and can help improve health outcomes. We conclude the review by discussing open problems in the field and promising directions for future research.

  1. HPV Vaccine PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  2. Vaccine independence, local competences and globalisation: lessons from the history of pertussis vaccines

    NARCIS (Netherlands)

    Blume, S.; Zanders, M.

    2006-01-01

    In the context of global vaccine politics ‘vaccine independence’ has been defined as the assumption of financial responsibility for vaccine procurement. This paper suggests ‘the possibility of vaccine choice’ as an alternative meaning for the term. How far does local competence in vaccine

  3. Vaccination of School Children With Live Mumps Virus Vaccine

    Science.gov (United States)

    Furesz, J.; Nagler, F. P.

    1970-01-01

    Live, attenuated mumps virus vaccine (Mumpsvax) was administered to 146 school children 6 to 9 years of age. One child developed clinical mumps nine days after vaccination; epidemiological and serological data strongly suggest that this child had become infected before vaccination. Apart from this single instance there were no apparent clinical reactions that could be ascribed to the administration of the vaccine. Sixty-three of the 146 children with no clinical history of mumps had an initial serum neutralizing antibody titre of less than 1:2. Specific antibodies to mumps virus were detected in 93.5% of the sera of the susceptible children 28 days after vaccination, and the geometric mean antibody titre of these sera was low (1:6). Of the 80 initially seropositive children 21 (26.2%) showed a significant antibody response to the vaccine and this was influenced by the pre-existing antibody level. These data have further demonstrated the safety and efficacy of the live mumps vaccine in children. PMID:5420994

  4. Serogroup B Meningococcal Vaccine (MenB)

    Science.gov (United States)

    What are meningococcal group B vaccines?Two serogroup B meningococcal group B vaccines (Bexsero and Trumenba) have been licensed by the Food and Drug ... Who should not get meningococcal group B vaccine or should wait?Tell the person ... you the vaccine:If you have any severe, life-threatening allergies. ...

  5. [Migrant vaccinations in Poland].

    Science.gov (United States)

    Sakowski, Piotr

    2012-01-01

    After the European Union accession in 2004, Poland has been perceived by foreigners as an attractive destination of their migration, and also as a popular transit country for people going further to the Western Europe countries. The Nofer Institute of Occupational Medicine is involved in the implementation of the international project PROMOVAX (Promote Vaccinations among Migrant Populations in Europe). The objective of the project is to promote immunizations among migrant populations in Europe. This article presents the up-to-date legal regulations that are effective in Poland, taking into account their relevance to the issue of vaccinations in migrant population. The analysis of the Polish legislation concerning this problem shows that there are no specific regulations addressed to migrant population staying in our country. This issue seems to be popular in the European Union, where immunization of migrants is given high priority. From the point of view of health care professionals it is important to be aware of the fact that EU open borders favor the increased flow of people between countries. The scale of migration from outside the EU to its member states also contributes to the increase in potential contacts between health care workers and migrants working in Poland.

  6. Development of Streptococcus agalactiae vaccines for tilapia.

    Science.gov (United States)

    Liu, Guangjin; Zhu, Jielian; Chen, Kangming; Gao, Tingting; Yao, Huochun; Liu, Yongjie; Zhang, Wei; Lu, Chengping

    2016-12-21

    Vaccination is a widely accepted and effective method to prevent most pathogenic diseases in aquaculture. Various species of tilapia, especially Nile tilapia Oreochromis niloticus, are farmed worldwide because of their high consumer demand. Recently, the tilapia-breeding industry has been hampered by outbreaks of Streptococcus agalactiae infection, which cause high mortality and huge economic losses. Many researchers have attempted to develop effective S. agalactiae vaccines for tilapia. This review provides a summary of the different kinds of S. agalactiae vaccines for tilapia that have been developed recently. Among the various vaccine types, inactivated S. agalactiae vaccines showed superior protection efficiency when compared with live attenuated, recombinant and DNA vaccines. With respect to vaccination method, injecting the vaccine into tilapia provided the most effective immunoprotection. Freund's incomplete adjuvant appeared to be suitable for tilapia vaccines. Other factors, such as immunization duration and number, fish size and challenge dose, also influenced the vaccine efficacy.

  7. New approaches in oral rotavirus vaccines.

    Science.gov (United States)

    Kuate Defo, Zenas; Lee, Byong

    2016-05-01

    Rotavirus is the leading cause of severe dehydrating diarrhea worldwide, and affects primarily developing nations, in large part because of the inaccessibility of vaccines and high rates of mortality present therein. At present, there exist two oral rotaviral vaccines, Rotarix™ and RotaTeq™. These vaccines are generally effective in their actions: however, associated costs often stymie their effectiveness, and they continue to be associated with a slight risk of intussusception. While different programs are being implemented worldwide to enhance vaccine distribution and monitor vaccine administration for possible intussusception in light of recent WHO recommendation, another major problem persists: that of the reduced efficacy of the existing rotaviral vaccines in developing countries over time. The development of new oral rotavirus vaccine classes - live-attenuated vaccines, virus-like particles, lactic acid bacteria-containing vaccines, combination therapy with immunoglobulins, and biodegradable polymer-encapsulated vaccines - could potentially circumvent these problems.

  8. Timeliness vaccination of measles containing vaccine and barriers to vaccination among migrant children in East China.

    Directory of Open Access Journals (Sweden)

    Yu Hu

    Full Text Available BACKGROUND: The reported coverage rates of first and second doses of measles containing vaccine (MCV are almost 95% in China, while measles cases are constantly being reported. This study evaluated the vaccine coverage, timeliness, and barriers to immunization of MCV1 and MCV2 in children aged from 8-48 months. METHODS: We assessed 718 children aged 8-48 months, of which 499 children aged 18-48 months in September 2011. Face to face interviews were administered with children's mothers to estimate MCV1 and MCV2 coverage rate, its timeliness and barriers to vaccine uptake. RESULTS: The coverage rates were 76.9% for MCV1 and 44.7% for MCV2 in average. Only 47.5% of surveyed children received the MCV1 timely, which postpone vaccination by up to one month beyond the stipulated age of 8 months. Even if coverage thus improves with time, postponed vaccination adds to the pool of unprotected children in the population. Being unaware of the necessity for vaccination and its schedule, misunderstanding of side-effect of vaccine, and child being sick during the recommended vaccination period were significant preventive factors for both MCV1 and MCV2 vaccination. Having multiple children, mother's education level, household income and children with working mothers were significantly associated with delayed or missing MCV1 immunization. CONCLUSIONS: To avoid future outbreaks, it is crucial to attain high coverage levels by timely vaccination, thus, accurate information should be delivered and a systematic approach should be targeted to high-risk groups.

  9. The role of attitudes about vaccine safety, efficacy, and value in explaining parents' reported vaccination behavior.

    Science.gov (United States)

    Lavail, Katherine Hart; Kennedy, Allison Michelle

    2013-10-01

    To explain vaccine confidence as it related to parents' decisions to vaccinate their children with recommended vaccines, and to develop a confidence measure to efficiently and effectively predict parents' self-reported vaccine behaviors. A sample of parents with at least one child younger than 6 years (n = 376) was analyzed using data from the HealthStyles 2010 survey. Questions were grouped into block variables to create three confidence constructs: value, safety, and efficacy. Regression equations controlling for demographic characteristics were used to identify the confidence construct(s) that best predicted parents' self-reported vaccination decisions (accept all, some, or none of the recommended childhood vaccines). Among the three constructs evaluated, confidence in the value of vaccines, that is the belief that vaccines are important and vaccinating one's children is the right thing to do, was the best predictor of parents' vaccine decisions, F(2, 351) = 119.199, p parents' self-reported vaccine decisions. Confidence in the safety or efficacy of vaccines failed to account for additional significant variance in parent-reported vaccination behavior. Confidence in the value of vaccines is a helpful predictor of parent-reported vaccination behavior. Attitudinal constructs of confidence in the safety and efficacy of vaccines failed to account for additional significant variance in parents' vaccination behaviors. Future research should assess the role of vaccine knowledge and tangible barriers, such as access and cost, to further explain parents' vaccination behaviors.

  10. The Evolution of Poxvirus Vaccines

    Science.gov (United States)

    Sánchez-Sampedro, Lucas; Perdiguero, Beatriz; Mejías-Pérez, Ernesto; García-Arriaza, Juan; Di Pilato, Mauro; Esteban, Mariano

    2015-01-01

    After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO) in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases. PMID:25853483

  11. 17DD yellow fever vaccine

    Science.gov (United States)

    Martins, Reinaldo M.; Maia, Maria de Lourdes S.; Farias, Roberto Henrique G.; Camacho, Luiz Antonio B.; Freire, Marcos S.; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C.; Lima, Sheila Maria B.; Nogueira, Rita Maria R.; Sá, Gloria Regina S.; Hokama, Darcy A.; de Carvalho, Ricardo; Freire, Ricardo Aguiar V.; Filho, Edson Pereira; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-01-01

    Objective: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. International Register ISRCTN 38082350. PMID:23364472

  12. Oral vaccination: where we are?

    Science.gov (United States)

    Silin, Dmytro S; Lyubomska, Oksana V; Jirathitikal, Vichai; Bourinbaiar, Aldar S

    2007-07-01

    As early as 900 years ago, the Bedouins of the Negev desert were reported to kill a rabid dog, roast its liver and feed it to a dog-bitten person for three to five days according to the size and number of bites [1] . In sixteenth century China, physicians routinely prescribed pills made from the fleas collected from sick cows, which purportedly prevented smallpox. One may dismiss the wisdom of the Bedouins or Chinese but the Nobel laureate, Charles Richet, demonstrated in 1900 that feeding raw meat can cure tuberculous dogs - an approach he termed zomotherapy. Despite historical clues indicating the feasibility of oral vaccination, this particular field is notoriously infamous for the abundance of dead-end leads. Today, most commercial vaccines are delivered by injection, which has the principal limitation that recipients do not like needles. In the last few years, there has been a sharp increase in interest in needle-free vaccine delivery; new data emerges almost daily in the literature. So far, there are very few licensed oral vaccines, but many more vaccine candidates are in development. Vaccines delivered orally have the potential to take immunization to a fundamentally new level. In this review, the authors summarize the recent progress in the area of oral vaccines.

  13. Decision support in vaccination policies.

    Science.gov (United States)

    Piso, B; Wild, C

    2009-10-09

    Looking across boarders reveals that the national immunization programs of various countries differ in their vaccination schedules and decisions regarding the implementation and funding of new vaccines. The aim of this review is to identify decision aids and crucial criteria for a rational decision-making process on vaccine introduction and to develop a theoretical framework for decision-making based on available literature. Systematic literature search supplemented by hand-search. We identified five published decision aids for vaccine introduction and program planning in industrialized countries. Their comparison revealed an overall similarity with some differences in the approach as well as criteria. Burden of disease and vaccine characteristics play a key role in all decision aids, but authors vary in their views on the significance of cost-effectiveness analyses. Other relevant factors that should be considered before vaccine introduction are discussed to highly differing extents. These factors include the immunization program itself as well as its conformity with other programs, its feasibility, acceptability, and equity, as well as ethical, legal and political considerations. Assuming that the most comprehensive framework possible will not provide a feasible tool for decision-makers, we suggest a stepwise procedure. Though even the best rational approach and most comprehensive evaluation is limited by remaining uncertainties, frameworks provide at least a structured approach to evaluate the various aspects of vaccine implementation decision-making. This process is essential in making consistently sound decisions and will facilitate the public's confidence in the decision and its realization.

  14. The Evolution of Poxvirus Vaccines

    Directory of Open Access Journals (Sweden)

    Lucas Sánchez-Sampedro

    2015-04-01

    Full Text Available After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV, the causative agent of smallpox. Cowpox virus (CPXV and horsepox virus (HSPV were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV, which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases.

  15. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  16. Public awareness regarding children vaccination in Jordan.

    Science.gov (United States)

    Masadeh, Majed M; Alzoubi, Karem H; Al-Azzam, Sayer I; Al-Agedi, Hassan S; Abu Rashid, Baraa E; Mukattash, Tariq L

    2014-01-01

    Immunization can contribute to a dramatic reduction in number of vaccine-preventable diseases among children. The aim of this study is to investigate mothers' awareness about child vaccines and vaccination in Jordan. This study was a community-based, cross-sectional study that was performed at public places in Irbid City. Data was collected from 506 mothers. After verbal approval, mothers were interviewed to assess their knowledge, attitudes, and practice toward vaccination. Results show that majority of mothers had acceptable knowledge and positive attitude toward vaccination. Most of mothers (94.7-86.8%) were able to identify vaccines that are mandatory as per the national vaccination program. Lower knowledge was observed among mothers (71.6%) for HIB vaccination being mandatory. Most mothers (97.2%) had vaccination card for their baby form the national vaccination programs. Vaccination delay was reported by about 36.6% of mothers and was shown to be associated with significantly (P = 0.001) lower vaccination knowledge/attitude score. Additionally, mothers who reported to be regularly offered information about vaccination during visits and those who identified medical staff members as their major information source had significantly higher vaccination knowledge/attitude score (P = 0.002). In conclusion, vaccination coverage rate is high; however, some aspects of knowledge, attitudes, and practice of vaccination need to be improved. Knowledge and attitudes of mothers were directly associated with their practice of vaccination. Medical staff education about vaccination during each visit seems to be the most effective tool that directly reflects on better practice of vaccination such as reducing the possibility for vaccination delay.

  17. Novel vaccines to human rabies.

    Directory of Open Access Journals (Sweden)

    Hildegund C J Ertl

    Full Text Available Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP. In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered.

  18. Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

    NARCIS (Netherlands)

    Kraan, H.; Have, Ten R.; Maas, van der L.; Kersten, G.F.A.; Amorij, J.P.

    2016-01-01

    A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick

  19. Do Vaccines Cause Autism? Is it OK to Skip Certain Vaccines? Get the facts

    Science.gov (United States)

    ... Lifestyle Infant and toddler health Do vaccines cause autism? Is it OK to skip certain vaccines? Get ... their potentially serious complications. Vaccines do not cause autism. Despite much controversy on the topic, researchers haven' ...

  20. Use of adenoviral vectors as veterinary vaccines.

    Science.gov (United States)

    Ferreira, T B; Alves, P M; Aunins, J G; Carrondo, M J T

    2005-10-01

    Vaccines are the most effective and inexpensive prophylactic tool in veterinary medicine. Ideally, vaccines should induce a lifelong protective immunity against the target pathogen while not causing clinical or pathological signs of diseases in the vaccinated animals. However, such ideal vaccines are rare in the veterinary field. Many vaccines are either of limited effectiveness or have harmful side effects. In addition, there are still severe diseases with no effective vaccines. A very important criterion for an ideal vaccine in veterinary medicine is low cost; this is especially important in developing countries and even more so for poultry vaccination, where vaccines must sell for a few cents a dose. Traditional approaches include inactivated vaccines, attenuated live vaccines and subunit vaccines. Recently, genetic engineering has been applied to design new, improved vaccines. Adenovirus vectors are highly efficient for gene transfer in a broad spectrum of cell types and species. Moreover, adenoviruses often induce humoral, mucosal and cellular immune responses to antigens encoded by the inserted foreign genes. Thus, adenoviruses have become a vector of choice for delivery and expression of foreign proteins for vaccination. Consequently, the market requirements for adenovirus vaccines are increasing, creating a need for production methodologies of concentrated vectors with warranted purity and efficacy. This review summarizes recent developments and approaches of adenovirus production and purification as the application of these vectors, including successes and failures in clinical applications to date.

  1. Development and trial of vaccines against Brucella.

    Science.gov (United States)

    Lalsiamthara, Jonathan; Lee, John Hwa

    2017-08-31

    The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most successful vaccine (S19) is only used in calves, as adult vaccination results in orchitis in male, prolonged infection, and possible abortion complications in pregnant female cattle. Another widely deployed vaccine (RB51) has a low protective efficacy. An ideal vaccine should exhibit a safe profile as well as enhance protective efficacy. However, currently available vaccines exhibit one or more major drawbacks. Smooth live attenuated vaccines suffer shortcomings such as residual virulence and serodiagnostic interference. Inactivated vaccines, in general, confer relatively low levels of protection. Recent developments to improve brucellosis vaccines include generation of knockout mutants by targeting genes involved in metabolism, virulence, and the lipopolysaccharide synthesis pathway, as well as generation of DNA vaccines, mucosal vaccines, and live vectored vaccines, have all produced varying degrees of success. Herein, we briefly review the bacteriology, pathogenesis, immunological implications, candidate vaccines, vaccinations, and models related to Brucella .

  2. Introducing dengue vaccine: Implications for diagnosis in dengue vaccinated subjects.

    Science.gov (United States)

    Alagarasu, Kalichamy

    2016-05-27

    Diagnosis of dengue virus infections is complicated by preference for different diagnostic tests in different post onset days of illness and the presence of multiple serotypes leading to secondary and tertiary infections. The sensitivity of the most commonly employed diagnostic assays such as anti dengue IgM capture (MAC) ELISA and non structural protein (NS) 1 capture ELISA are lower in secondary and subsequent infections. Introduction of dengue vaccine in endemic regions will affect the way how dengue is diagnosed in vaccinated subjects. This viewpoint article discusses implications of introduction of dengue vaccine on the diagnosis of dengue infections in vaccinated subjects and the strategies that are needed to tackle the issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The Impact of Making Vaccines Thermostable in Niger’s Vaccine Supply Chain

    Science.gov (United States)

    Lee, Bruce Y.; Cakouros, Brigid E.; Assi, Tina-Marie; Connor, Diana L.; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R.; Pierre, Lionel; Brown, Shawn T.

    2012-01-01

    Objective Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Methods Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Findings Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1–2%. Conclusion Our study shows the potential benefits of making any of Niger’s EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. PMID:22789507

  4. The impact of making vaccines thermostable in Niger's vaccine supply chain.

    Science.gov (United States)

    Lee, Bruce Y; Cakouros, Brigid E; Assi, Tina-Marie; Connor, Diana L; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R; Pierre, Lionel; Brown, Shawn T

    2012-08-17

    Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1-2%. Our study shows the potential benefits of making any of Niger's EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

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    O. A. Shamsutdinova

    2017-01-01

    Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine

  6. Status of vaccine research and development of vaccines for leishmaniasis.

    Science.gov (United States)

    Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

    2016-06-03

    A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  7. Egg-Independent Influenza Vaccines and Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Ilaria Manini

    2017-07-01

    Full Text Available Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.

  8. Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

    Science.gov (United States)

    Premenko-Lanier, Mary; Rota, Paul; Rhodes, Gary; Bellini, William; McChesney, Michael

    2004-01-26

    The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

  9. Reasons for non-vaccination: Parental vaccine hesitancy and the childhood influenza vaccination school pilot programme in England.

    Science.gov (United States)

    Paterson, Pauline; Chantler, Tracey; Larson, Heidi J

    2017-08-14

    In 2013, the annual influenza immunisation programme in England was extended to children to reduce the burden of influenza, but uptake was sub-optimal at 53.2%. To explore the reasons some parents decided not to vaccinate their child against influenza as part of the pilot programme offered in schools. Cross-sectional qualitative study conducted between February and July 2015. 913 parents whose children were not vaccinated against influenza in the school pilots in West Yorkshire and Greater Manchester, England, were asked to comment on their reasons for non-vaccination and invited to take part in a semi-structured interview. 138 parents returned response forms, of which 38 were eligible and interested in participating and 25 were interviewed. Interview transcripts were coded by theme in NVivo. A third of parents who returned response forms had either vaccinated their child elsewhere, intended to have them vaccinated, or had not vaccinated them due to medical reasons (valid or perceived). Most interviewees were not convinced of the need to vaccinate their child against influenza. Parents expressed concerns about influenza vaccine effectiveness and vaccine side effects. Several parents interviewed declined the vaccine for faith reasons due to the presence of porcine gelatine in the vaccine. To significantly decrease the burden of influenza in England, influenza vaccination coverage in children needs to be >60%. Hence, it is important to understand the reasons why parents are not vaccinating their children, and to tailor the communication and immunisation programme accordingly. Our finding that a third of parents, who did not consent to their child being vaccinated as part of the school programme, had actually vaccinated their child elsewhere, intended to have their child vaccinated, or had not vaccinated them due to medical reasons, illustrates the importance of including additional questions or data sources when investigating under-vaccination. Copyright © 2017 The

  10. VACCINES AND IMMUNIZATION: WORLD SITUATION

    Directory of Open Access Journals (Sweden)

    G.H. Brundtland

    2007-01-01

    Full Text Available The last issue of the report «vaccines and immunization: world situation» stresses considerable success in immunization at the global level since the mid 90 s — completely total eradication of poliomyelitis across the world, as well as the drastic reduction of the new measles and tetanus cases among mothers and newborns in some poor countries. The report also briefly describes the progress in the development and implementation of the new life saving vaccines, which may save millions of lives annually. The authors have explained some of the reasons, why the global community should invest in immunization, as well as the perspectives for the use of vaccines and immunization in future.Key words: vaccine, immunization, children.

  11. Neurologic Complications of Smallpox Vaccination

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-06-01

    Full Text Available Smallpox and smallpox vaccination is reviewed from the Departments of Neurology, Yale University School of Medicine, New Haven, CT, and University of New Mexico School of Medicine, Albuquerque.

  12. Flu Vaccine Skin Patch Tested

    Science.gov (United States)

    ... Subscribe September 2017 Print this issue Health Capsule Flu Vaccine Skin Patch Tested En español Send us ... Each year, millions of people nationwide catch the flu. The best way to protect yourself is to ...

  13. What Vaccinations Do You Need?

    Science.gov (United States)

    ... disease that is common to that area. (See chart below for a list of vaccinations commonly recommended ... Talking to Your Friends About Kidney Disease The Dental / Kidney Disease Connection Travel Tips: A Guide for ...

  14. EDITORIAL CONTRIBUTION OF VACCINATIONS TOWARDS ...

    African Journals Online (AJOL)

    hi-tech

    2003-01-01

    Jan 1, 2003 ... procurement and delivery of the vaccines to the target .... A new state-of-the-art facility for frontline health workers, ... CURRENT CRITICAL MEDICAL AND PUBLIC HEALTH ... P.O Box 41632, Code 00100, GPO, NAIROBI.

  15. Diabetes and Hepatitis B Vaccination

    Science.gov (United States)

    Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

  16. Adenovirus-vectored Ebola vaccines.

    Science.gov (United States)

    Gilbert, Sarah C

    2015-01-01

    The 2014 outbreak of Ebola virus disease in West Africa has highlighted the need for the availability of effective vaccines against outbreak pathogens that are suitable for use in frontline workers who risk their own health in the course of caring for those with the disease, and also for members of the community in the affected area. Along with effective contact tracing and quarantine, use of a vaccine as soon as an outbreak is identified could greatly facilitate rapid control and prevent the outbreak from spreading. This review describes the progress that has been made in producing and testing adenovirus-based Ebola vaccines in both pre-clinical and clinical studies, and considers the likely future use of these vaccines.

  17. Viral hepatitis vaccination during pregnancy.

    Science.gov (United States)

    Zhao, Yueyuan; Jin, Hui; Zhang, Xuefeng; Wang, Bei; Liu, Pei

    2016-04-02

    Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy.

  18. Preventable Pediatric Stroke via Vaccination?

    Directory of Open Access Journals (Sweden)

    Craig A. Press

    2015-11-01

    Full Text Available Investigators from the Vascular Effects of Infection in Pediatric Stroke (VIPS group studied the risk of arterial ischemic stroke (AIS associated with minor infection and routine childhood vaccinations.

  19. Flublok Seasonal Influenza (Flu) Vaccination

    Science.gov (United States)

    ... type="submit" value="Submit" /> Archived Flu Emails Influenza Types Seasonal Avian Swine Variant Pandemic Other Flublok Seasonal Influenza (Flu) Vaccine Questions & Answers Language: English (US) Español ...

  20. Veterinary vaccines against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Elisabeth A Innes

    2009-03-01

    Full Text Available Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.

  1. VACCINATION OF CHILDREN WITH MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    D.Yu. Kachanov

    2010-01-01

    Full Text Available Children suffering from oncological diseases fall into the group of immunocompromised patients. They are more at risk of severe children’s banal infections. Development of safe and efficient methods for immunological prevention of preventable infections diseases in this group of children is one of priorities for modern medicine. It is also important to properly organise the process of vaccinating the persons surrounding the patient to eliminate the risk of postvaccinal complications in the sick (non-vaccinated child. The article provides a detailed overview of the global experience in vaccinating children with malignant neoplasms. It describes modern principles of immunological prevention in children both being administered the standard anticancer therapy and those have undergone transplantation of hemopoietic stem cells. Key words: children, malignancy, vaccination.(Pediatric Pharmacology. – 2010; 7(3:28-34

  2. Vaccination Confidence and Parental Refusal/Delay of Early Childhood Vaccines.

    Directory of Open Access Journals (Sweden)

    Melissa B Gilkey

    Full Text Available To support efforts to address parental hesitancy towards early childhood vaccination, we sought to validate the Vaccination Confidence Scale using data from a large, population-based sample of U.S. parents.We used weighted data from 9,354 parents who completed the 2011 National Immunization Survey. Parents reported on the immunization history of a 19- to 35-month-old child in their households. Healthcare providers then verified children's vaccination status for vaccines including measles, mumps, and rubella (MMR, varicella, and seasonal flu. We used separate multivariable logistic regression models to assess associations between parents' mean scores on the 8-item Vaccination Confidence Scale and vaccine refusal, vaccine delay, and vaccination status.A substantial minority of parents reported a history of vaccine refusal (15% or delay (27%. Vaccination confidence was negatively associated with refusal of any vaccine (odds ratio [OR] = 0.58, 95% confidence interval [CI], 0.54-0.63 as well as refusal of MMR, varicella, and flu vaccines specifically. Negative associations between vaccination confidence and measures of vaccine delay were more moderate, including delay of any vaccine (OR = 0.81, 95% CI, 0.76-0.86. Vaccination confidence was positively associated with having received vaccines, including MMR (OR = 1.53, 95% CI, 1.40-1.68, varicella (OR = 1.54, 95% CI, 1.42-1.66, and flu vaccines (OR = 1.32, 95% CI, 1.23-1.42.Vaccination confidence was consistently associated with early childhood vaccination behavior across multiple vaccine types. Our findings support expanding the application of the Vaccination Confidence Scale to measure vaccination beliefs among parents of young children.

  3. Economic value of dengue vaccine in Thailand.

    Science.gov (United States)

    Lee, Bruce Y; Connor, Diana L; Kitchen, Sarah B; Bacon, Kristina M; Shah, Mirat; Brown, Shawn T; Bailey, Rachel R; Laosiritaworn, Yongjua; Burke, Donald S; Cummings, Derek A T

    2011-05-01

    With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

  4. Influenza vaccines: Evaluation of the safety profile

    Science.gov (United States)

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

    2018-01-01

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

  5. Application of radiation technology in vaccines development.

    Science.gov (United States)

    Seo, Ho Seong

    2015-07-01

    One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology.

  6. Zika Vaccine Development: Flavivirus Foils

    Science.gov (United States)

    2016-09-01

    Martins, Bavari, Zika Vaccine Development 1 Zika Vaccine Development: Flavivirus Foils Martins KAO, Bavari S. The current Zika virus...States government. The rapid response to Zika is perhaps the first of its kind, and it undoubtedly has been made possible by the lessons learned from...the response to the 2014 Ebola virus outbreak in West Africa. However, Zika virus is not Ebola virus. As of February 2016 there were only 296

  7. [Towards a new vaccine economy?].

    Science.gov (United States)

    Poirot, P; Martin, J F

    1994-01-01

    When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Is an HIV vaccine possible?

    Directory of Open Access Journals (Sweden)

    Nancy A. Wilson

    Full Text Available The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5 expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.

  9. Is an HIV vaccine possible?

    OpenAIRE

    Wilson,Nancy A.; Watkins,David I.

    2009-01-01

    The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against h...

  10. Value in assessing new vaccines

    Directory of Open Access Journals (Sweden)

    Giuseppe La Torre

    2009-09-01

    Full Text Available Vaccination strategies are recognised as one of the most powerful interventions in the field of Public health worldwide, capable of reducing both morbidity and mortality. There is wide availability of new vaccines, at least in Developed Countries, that have the potential to control infectious diseases, while on the other hand there are new vaccines that will become available in the next few years. This paper aims to describe the different perspectives one could take into account in valuing particularly new vaccines. The epidemiological approach has been one of underlying principles in setting priorities for immunization programs. The introduction in the health market of a new vaccine is based on the assessment of the related burden of infection/disease and the consequent impact on population health. In the economic evaluation approach several types of analysis are available. The budget impact analysis is concerned more with the immediate impact; in this sense cost is considered instead of value as well as giving higher consideration to short-term effects, while cost-effectiveness or cost-utility analysis can be utilised to examine effects in the long term. In the field of vaccinations a public approach through the use of media campaigns or non-profit organisations, might or might not push politicians and physicians to take action to address a perceived health problem via a vaccine. A Health Technology Assessment approach has been developed in some European countries to examine, in a multidisciplinary way, the clinical, economic, organizational, ethical, juridical, social and cultural implications of the introduction or the implementation of a specific technology. The HTA approach in Italy was demonstrated to be a comprehensive tool in assessing the introduction of a new vaccine, giving insight to the issue to several stakeholders, i.e. decision makers, researchers, and patients.

  11. Validation of the vaccine conspiracy beliefs scale.

    Science.gov (United States)

    Shapiro, Gilla K; Holding, Anne; Perez, Samara; Amsel, Rhonda; Rosberger, Zeev

    2016-12-01

    Parents' vaccine attitudes influence their decision regarding child vaccination. To date, no study has evaluated the impact of vaccine conspiracy beliefs on human papillomavirus vaccine acceptance. The authors assessed the validity of a Vaccine Conspiracy Beliefs Scale (VCBS) and determined whether this scale was associated with parents' willingness to vaccinate their son with the HPV vaccine. Canadian parents completed a 24-min online survey in 2014. Measures included socio-demographic variables, HPV knowledge, health care provider recommendation, Conspiracy Mentality Questionnaire (CMQ), the seven-item VCBS, and parents' willingness to vaccinate their son at two price points. A total of 1427 Canadian parents completed the survey in English (61.2%) or French (38.8%). A Factor Analysis revealed the VCBS is one-dimensional and has high internal consistency (α=0.937). The construct validity of the VCBS was supported by a moderate relationship with the CMQ (r=0.44, pparents' willingness to vaccinate their son with the HPV vaccine at both price points ('free' or '$300') after controlling for gender, age, household income, education level, HPV knowledge, and health care provider recommendation. The VCBS is a brief, valid scale that will be useful in further elucidating the correlates of vaccine hesitancy. Future research could use the VCBS to evaluate the impact of vaccine conspiracies beliefs on vaccine uptake and how concerns about vaccination may be challenged and reversed. Copyright © 2016. Published by Elsevier B.V.

  12. Differences in HIV vaccine acceptability between genders

    Science.gov (United States)

    Kakinami, Lisa; Newman, Peter A.; Lee, Sung-Jae; Duan, Naihua

    2010-01-01

    The development of safe and efficacious preventive HIV vaccines offers the best long-term hope of controlling the AIDS pandemic. Nevertheless, suboptimal uptake of safe and efficacious vaccines that already exist suggest that HIV vaccine acceptability cannot be assumed, particularly among communities most vulnerable to HIV. The present study aimed to identify barriers and motivators to future HIV vaccine acceptability among low socioeconomic, ethnically diverse men and women in Los Angeles County. Participants completed a cross-sectional survey assessing their attitudes and beliefs regarding future HIV vaccines. Hypothetical HIV vaccine scenarios were administered to determine HIV vaccine acceptability. Two-sided t-tests were performed, stratified by gender, to examine the association between vaccine acceptability and potential barriers and motivators. Barriers to HIV vaccine acceptability differed between men and women. For women, barriers to HIV vaccine acceptability were related to their intimate relationships (p Motivators for women included the ability to conceive a child without worrying about contracting HIV (p Motivators for men included feeling safer with sex partners (p motivator for both men and women (p <0.10). Gender-specific interventions may increase vaccine acceptability among men and women at elevated risk for HIV infection. Among women, interventions need to focus on addressing barriers due to gendered power dynamics in relationships and discrimination in health care. Among men, education that addresses fears and misconceptions about adverse effects of HIV vaccination on health and the importance of vaccination as one component of integrated HIV prevention may increase vaccine acceptability. PMID:18484322

  13. Polio and the Vaccine (Shot) to Prevent It

    Science.gov (United States)

    ... and Teen Vaccine Resources Related Links Vaccines & Immunizations Polio and the Vaccine (Shot) to Prevent It Language: ... recommend all children get the vaccine. What is polio? Polio (or poliomyelitis) is a disease caused by ...

  14. Adult Vaccinations | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Adult Vaccinations Adults Need Vaccines, Too! Past Issues / Summer 2015 Table ... cough). Are you one of the millions of adults not receiving the vaccines you need? What vaccines ...

  15. Effect of School-based Human Papillomavirus (HPV) Vaccination on ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    assessed girls' knowledge of cervical cancer and HPV vaccine, and their acceptance of future vaccination of ... studies involve parents and young adults. The ... vaccine was delivered during the routine Child ... and attitudes about the vaccine.

  16. Vaccines Stop Illness | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Diseases and Vaccinations Vaccines Stop Illness Past Issues / Spring 2015 Table of ... like polio and meningitis will affect their children. Vaccine Safety In light of recent questions about vaccine ...

  17. [Vaccine against human papilloma virus].

    Science.gov (United States)

    Juárez-Albarrán, Alfredo César; Juárez-Gámez, Carlos Alberto

    2008-01-01

    Genital human papilloma virus infection (HPV) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in America, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. This review examines the most important actual facts about HPV infection, and the new prophylactic vaccines. Two versions of the vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. One of them also targets HPV 6 and HPV 11, which account for approximately 90% of external genital warts. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. The role of men as carriers of HPV as well as vectors for transmission is well documented. Several clinical trials are currently under way to determine the efficacy of vaccinating men. Reducing the cost of vaccination would be a priority for the developing world in order to get a broad target in poor countries.

  18. Strategies for Cancer Vaccine Development

    Directory of Open Access Journals (Sweden)

    Matteo Vergati

    2010-01-01

    Full Text Available Treating cancer with vaccines has been a challenging field of investigation since the 1950s. Over the years, the lack of effective active immunotherapies has led to the development of numerous novel strategies. However, the use of therapeutic cancer vaccines may be on the verge of becoming an effective modality. Recent phase II/III clinical trials have achieved hopeful results in terms of overall survival. Yet despite these encouraging successes, in general, very little is known about the basic immunological mechanisms involved in vaccine immunotherapy. Gaining a better understanding of the mechanisms that govern the specific immune responses (i.e., cytotoxic T lymphocytes, CD4 T helper cells, T regulatory cells, cells of innate immunity, tumor escape mechanisms elicited by each of the various vaccine platforms should be a concern of cancer vaccine clinical trials, along with clinical benefits. This review focuses on current strategies employed by recent clinical trials of therapeutic cancer vaccines and analyzes them both clinically and immunologically.

  19. Tuberculosis: looking beyond BCG vaccines.

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    Mustafa Abu S

    2003-01-01

    Full Text Available Tuberculosis (TB is an infectious disease of international importance and ranks among the top 10 causes of death in the World. About one-third of the world′s population is infected with Mycobacterium tuberculosis. Every year, approximately eight million people develop active disease and two million die of TB. The currently used BCG vaccines have shown variable protective efficacies against TB in different parts of the world. Moreover, being a live vaccine, BCG can be pathogenic in immunocompromised recipients. Therefore, there is an urgent need to develop new vaccines against TB. The comparative genome analysis has revealed the existence of several M. tuberculosis-specific regions that are deleted in BCG. The work carried out to determine the immunological reactivity of proteins encoded by genes located in these regions revealed several major antigens of M. tuberculosis, including the 6 kDa early secreted antigen target (ESAT6. Immunization with ESAT6 and its peptide (aa51-70 protects mice challenged with M. tuberculosis. The protective efficacy of immunization further improves when ESAT6 is recombinantly fused with M. tuberculosis antigen 85B. In addition, ESAT6 delivered as a DNA vaccine is also protective in mice. Whether these vaccines would be safe or not cannot be speculated. The answer regarding the safety and efficacy of these vaccines has to await human trials in different parts of the world.

  20. Adolescent Male Human Papillomavirus Vaccination

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    Vivian C. Nanagas MD, MSc

    2016-04-01

    Full Text Available Objective. To determine male vaccination rates with quadrivalent human papillomavirus vaccine (HPV4 before and after the October 2011 national recommendation to routinely immunize adolescent males. Methods. We reviewed HPV4 dose 1 (HPV4-1 uptake in 292 adolescent males in our urban clinic prior to national recommendations and followed-up for HPV4 series completion rates. After national recommendation, 248 urban clinic and 247 suburban clinic males were reviewed for HPV4-1 uptake. Factors associated with HPV4-1 refusal were determined with multiple logistic regression. Results. Of the initial 292 males, 78% received HPV4-1 and 38% received the 3-dose series. After recommendation, HPV4-1 uptake was 59% and 7% in urban and suburban clinics, respectively. Variables associated with HPV4-1 uptake/refusal included time period, race, type of insurance, and receipt of concurrent vaccines. Conclusions. HPV4-1 vaccination rates in our urban clinic were high before and after routine HPV vaccine recommendations for adolescent males. Our vaccination rates were much higher than in a suburban practice.