WorldWideScience

Sample records for licensed smallpox vaccine

  1. Smallpox and smallpox vaccine: ocular and systemic risks and ethical uncertainties.

    Science.gov (United States)

    Chous, A Paul; Hom, Gregory G

    2003-09-01

    The threat of bioterrorism and use of biological weapons has drawn renewed attention to smallpox, and smallpox vaccinations have been resumed in the United States. Both smallpox and smallpox vaccine carry risk of potentially debilitating or fatal adverse effects. The optometrist must be familiar with the signs and symptoms of smallpox disease and complications of smallpox vaccine for proper management and preservation of vision. The literature on the ocular and systemic effects of smallpox and smallpox vaccination is reviewed to provide the practicing optometrist with an overview of the issues involved in case management. Recent guidelines have placed additional ocular-related contraindications to receiving the smallpox vaccine. Risk factors for complications arising from smallpox vaccination are discussed. A discussion of the ethical implications is also presented. Knowledge of the signs and symptoms of smallpox infection, and of adverse effects caused by smallpox vaccination, can provide the necessary background to help eye care providers make appropriate diagnoses and referrals. Understanding ethical and legal/Constitutional questions surrounding the risk of outbreak and various vaccination containment strategies will help optometrists make informed decisions as health care professionals, patient advocates, and concerned citizens, as well as weigh the risks and benefits of vaccination, if it is offered to them.

  2. [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.

  3. Countermeasures and vaccination against terrorism using smallpox: pre-event and post-event smallpox vaccination and its contraindications.

    Science.gov (United States)

    Sato, Hajime

    2011-09-01

    Smallpox, when used as a biological weapon, presents a serious threat to civilian populations. Core components of the public health management of a terrorism attack using smallpox are: vaccination (ring vaccination and mass vaccination), adverse event monitoring, confirmed and suspected smallpox case management, contact management, identifying, tracing, monitoring contacts, and quarantine. Above all, pre-event and post-event vaccination is an indispensable part of the strategies. Since smallpox patients are most infectious from onset of the rash through the first 7-10 days of the rash, vaccination should be administered promptly within a limited time frame. However, vaccination can accompany complications, such as postvaccinial encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia. Therefore, vaccination is not recommended for certain groups. Public health professionals, as well as physicians and government officials, should also be well equipped with all information necessary for appropriate and effective smallpox management in the face of such a bioterrorism attack.

  4. 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.

  5. Smallpox: clinical highlights and considerations for vaccination.

    Directory of Open Access Journals (Sweden)

    Mahoney M

    2003-01-01

    Full Text Available Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox vaccine is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessary. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population.

  6. ACAM2000™: The new smallpox vaccine for United States Strategic National Stockpile

    Directory of Open Access Journals (Sweden)

    Aysegul Nalca

    2010-05-01

    Full Text Available Aysegul Nalca, Elizabeth E ZumbrunCenter for Aerobiological Sciences, US Army Medical Research Institute of Infectious Diseases (USAMRIID, Fort Detrick, MD, USAAbstract: Smallpox was eradicated more than 30 years ago, but heightened concerns over bioterrorism have brought smallpox and smallpox vaccination back to the forefront. The previously licensed smallpox vaccine in the United States, Dryvax® (Wyeth Laboratories, Inc., was highly effective, but the supply was insufficient to vaccinate the entire current US population. Additionally, Dryvax® had a questionable safety profile since it consisted of a pool of vaccinia virus strains with varying degrees of virulence, and was grown on the skin of calves, an outdated technique that poses an unnecessary risk of contamination. The US government has therefore recently supported development of an improved live vaccinia virus smallpox vaccine. This initiative has resulted in the development of ACAM2000™ (Acambis, Inc.™, a single plaque-purified vaccinia virus derivative of Dryvax®, aseptically propagated in cell culture. Preclinical and clinical trials reported in 2008 demonstrated that ACAM2000™ has comparable immunogenicity to that of Dryvax®, and causes a similar frequency of adverse events. Furthermore, like Dryvax®, ACAM2000™ vaccination has been shown by careful cardiac screening to result in an unexpectedly high rate of myocarditis and pericarditis. ACAM2000™ received US Food and Drug Administration (FDA approval in August 2007, and replaced Dryvax® for all smallpox vaccinations in February 2008. Currently, over 200 million doses of ACAM2000™ have been produced for the US Strategic National Stockpile. This review of ACAM2000™ addresses the production, characterization, clinical trials, and adverse events associated with this new smallpox vaccine.Keywords: smallpox, vaccinia, variola, vaccine, efficacy, safety

  7. The immunology of smallpox vaccines

    Science.gov (United States)

    Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

    2010-01-01

    In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

  8. Smallpox vaccines: targets of protective immunity.

    Science.gov (United States)

    Moss, Bernard

    2011-01-01

    The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new-generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second- and third-generation smallpox vaccines. Published 2010. This article is a US Government work and is in the public domain in the USA.

  9. 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.

  10. Smallpox vaccination and all-cause infectious disease hospitalization

    DEFF Research Database (Denmark)

    Sørup, Signe; Villumsen, Marie; Ravn, Henrik

    2011-01-01

    There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark, ......, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections.......There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark...

  11. Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.

    Science.gov (United States)

    Casey, Christine; Vellozzi, Claudia; Mootrey, Gina T; Chapman, Louisa E; McCauley, Mary; Roper, Martha H; Damon, Inger; Swerdlow, David L

    2006-02-03

    CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case

  12. The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

    Science.gov (United States)

    Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

    2013-10-25

    Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. 76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

    Science.gov (United States)

    2011-08-11

    ...] The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop AGENCY: Food and... Evaluation of Next-Generation Smallpox Vaccines.'' The purpose of the public workshop is to identify and discuss the key issues related to the development and evaluation of next-generation smallpox vaccines. The...

  14. Smallpox vaccination and adverse reactions. Guidance for clinicians.

    Science.gov (United States)

    Cono, Joanne; Casey, Christine G; Bell, David M

    2003-02-21

    The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and

  15. 75 FR 3244 - Prospective Grant of Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses

    Science.gov (United States)

    2010-01-20

    ... Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses AGENCY: National Institutes of.... SUPPLEMENTARY INFORMATION: Concerns that variola (smallpox) virus might be used as a biological weapon have led... safe and effective for prevention of smallpox, it is well documented that various adverse reactions in...

  16. Fertility and early-life mortality: Evidence from smallpox vaccination in Sweden

    DEFF Research Database (Denmark)

    Ager, Philipp; Hansen, Casper Worm; Jensen, Peter Sandholt

    2018-01-01

    The smallpox vaccination method was the paramount medical innovation of the late 18th and early 19th centuries. We exploit the introduction of the smallpox vaccine in Sweden to identify the causal effect of early-life mortality on fertility. Our analysis shows that parishes in counties with highe...... a small insignificant effect on the number of surviving children and natural population growth....

  17. Evaluation of smallpox vaccines using variola neutralization.

    Science.gov (United States)

    Damon, Inger K; Davidson, Whitni B; Hughes, Christine M; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Frey, Sharon E; Newman, Frances; Belshe, Robert B; Yan, Lihan; Karem, Kevin

    2009-08-01

    The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

  18. Smallpox virus destruction and the implications of a new vaccine.

    Science.gov (United States)

    Henderson, D A

    2011-06-01

    The World Health Assembly is scheduled to decide in May 2011 whether the 2 known remaining stockpiles of smallpox virus are to be destroyed or retained. In preparation for this, a WHO-appointed committee undertook a comprehensive review of the status of smallpox virus research from 1999 to 2010. It concluded that, considering the nature of the studies already completed with respect to vaccine, drugs, and diagnostics, there was no reason to retain live smallpox virus except to satisfy restrictive regulatory requirements. The committee advised that researchers and regulators define alternative models for testing the vaccines and drugs. Apart from other considerations, the costs of new products are significant and important. These include prospective expenditures required for the development, manufacture, testing, and storage of new products. This commentary provides approximations of these costs and the incremental contribution that a newly developed vaccine might make in terms of public health security.

  19. Vaccine Basics (Smallpox)

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Smallpox Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Smallpox About Smallpox History of Smallpox Spread and Eradication ...

  20. 42 CFR 102.54 - Documentation the representative of the estate of a deceased smallpox vaccine recipient or...

    Science.gov (United States)

    2010-10-01

    ... deceased smallpox vaccine recipient or vaccinia contact must submit to be deemed eligible by the Secretary... VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.54 Documentation the representative of the estate of a deceased smallpox vaccine recipient or vaccinia contact must...

  1. [The late media emergency of smallpox vaccine, news coverage of Spanish press (1999-2004)].

    Science.gov (United States)

    Martínez-Martínez, Pedro Javier; Tuells, José; Colmenar-Jarillo, Gema

    2015-06-01

    Discussions on the need for smallpox virus preservation in 1999 focused attention on an eradicated disease 20 years ago. Smallpox was replaced as a potential candidate to be used as a bioterrorist weapon because of the international alarm scenario produced after the 11/9 events in USA. The reactivation of a vaccine which remained forgotten was the direct consequence. The initial target groups were the security forces of America. Spain was also among the countries that were interested in acquiring the smallpox vaccine. The aim of this study is to analyze the considerable media coverage of smallpox obtained in our country. Systematic review of published news in the four largest national daily newspapers (ABC, El Mundo, El País and La Vanguardia) for the period 1999-2004 of the Dow Jones Factiva document database. "Smallpox" were used as a key word. From the obtained data, a qualitative and quantitative analysis was done. 416 reviews were analyzed; the newspaper El Mundo was the most interested in these news (158 citations, 37.98%). Most of the news were published in 2003 (152, 36.5%) The year with more news about smallpox (2003) coincides with the purchase of vaccines in Spain. The type of messages in the news was highly changeable over this six-year period. Those related to "politics and diplomacy", "epidemiological risk", "bioterrorism" and "vaccine" were predominant. The alarm raised around the smallpox vaccination was a media phenomenon due to political strategy issues rather than a real public health problem.

  2. 42 CFR 102.51 - Documentation a smallpox vaccine recipient must submit to be deemed eligible by the Secretary.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Documentation a smallpox vaccine recipient must..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.51 Documentation a smallpox vaccine recipient must submit to be deemed eligible by...

  3. Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection.

    Science.gov (United States)

    Duraffour, Sophie; Andrei, Graciela; Snoeck, Robert

    2010-03-01

    Since the eradication of naturally occurring smallpox in 1980, the fear that variola virus could be used as a biological weapon has become real. Over the last 10 years, emergency preparedness programs have been launched to protect populations against a smallpox outbreak or the possible emergence in humans of other orthopoxvirus infections, such as monkeypox. Vaccination against smallpox was responsible for its eradication, but was linked with high rates of adverse events and contraindications. In this context, intensive research in the poxvirus field has led to the development of safer vaccines and to an increase in the number of anti-poxvirus agents in the pipeline. SIGA Technologies Inc, under license from ViroPharma Inc, is developing tecovirimat (ST-246). Tecovirimat is a novel antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. The development of tecovirimat during the last 5 years for the treatment of smallpox and for its potential use as adjunct to smallpox vaccine is reviewed here.

  4. What Is Smallpox?

    Science.gov (United States)

    ... and don't need to — get a smallpox vaccine right now, there is a supply of the vaccine in ... become infected with the smallpox virus, getting the vaccine within a few days of becoming infected can lessen the disease's symptoms. ...

  5. Challenges and Achievements in Prevention and Treatment of Smallpox

    Directory of Open Access Journals (Sweden)

    Sharon Melamed

    2018-01-01

    Full Text Available Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV, and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions.

  6. Introduction: simultaneously global and local: reassessing smallpox vaccination and its spread, 1789-1900.

    Science.gov (United States)

    Bhattacharya, Sanjoy; Brimnes, Niels

    2009-01-01

    The last two decades have seen a reawakening of scholarly interest in the history of smallpox prevention. Accounts of vaccination and others efforts at controlling smallpox have moved away from heroic narratives toward more nuanced and contextualized understandings. It is now accepted that several viruses traveled under the vaccine label from the outset, and it has been demonstrated that a variety of techniques were used to perform vaccination operations. The character of nineteenth century sea voyages that took the vaccine to distant territories has also been re-examined; sometimes the spread of the vaccine was caused by private networks and ad hoc decisions, while at other times it was the result of enterprises with close resemblances to contemporary centralized vaccination campaigns. Looking beyond Europe and North America we encounter a variety of state attitudes toward vaccination, ranging from concentrated efforts to spread the technique to efforts more uncertain and diluted. Although the reluctance to accept vaccination has been amply documented, recent studies emphasize this should not be attributed to simplistic dichotomies of modernity versus tradition or science versus culture; instead, instances of resistance are best studied as specific contextualized interactions. Indeed, factors like favorable geography, strong bureaucratic structures, and the absence of variolation seem to have helped the relatively smooth transfer of vaccination technologies. Perhaps most important, recent research encourages us to continue to study smallpox vaccination as a phenomenon that was simultaneously global and local.

  7. Risks of serious complications and death from smallpox vaccination: A systematic review of the United States experience, 1963–1968

    OpenAIRE

    Aragón, Tomás J; Ulrich, Skylar; Fernyak, Susan; Rutherford, George W

    2003-01-01

    Abstract Background The United States (US) has re-instituted smallpox vaccinations to prepare for an intentional release of the smallpox virus into the civilian population. In an outbreak, people of all ages will be vaccinated. To prepare for the impact of large-scale ring and mass vaccinations, we conducted a systematic review of the complication and mortality risks of smallpox vaccination. We summarized these risks for post-vaccinial encephalitis, vaccinia necrosum (progressive vaccinia), e...

  8. [About smallpox and vaccination practices in Minas Gerais (Brazil) in the 19th century].

    Science.gov (United States)

    Silveira, Anny Jackeline Torres; Marques, Rita de Cássia

    2011-02-01

    This article discusses the impact of smallpox and vaccination practices used against the disease used in the province of Minas Gerais, in Brazil, during the Imperial Period (1822-1889). Despite the existence of services responsible for the organization and dissemination of the vaccine in the country since the early 19th century, some administrative and cultural factors, as identified in documents produced by the province's public health authorities at the time, had a negative impact upon the full implementation of both practice and organization of services aimed at the dissemination of smallpox vaccination. Based upon historiographic sources, it is argued that despite the trend towards centralization observed at different governmental spheres during the structuring of the Imperial State, in particular, in the provision of vaccination services, there was a prevailing disharmony between the different agencies responsible for the implementation and management of such services. A further contributor to the difficulties in the service implementation was the resistance of the population to submit to the vaccination, a phenomenon that can be best understood through examination of the social construction of perceptions about diseases and the vaccination method used against the smallpox.

  9. Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study

    DEFF Research Database (Denmark)

    Villumsen, Marie; Sørup, Signe; Jess, Tine

    2009-01-01

    Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines...... cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.......31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas....

  10. Analysis of variola and vaccinia virus neutralization assays for smallpox vaccines.

    Science.gov (United States)

    Hughes, Christine M; Newman, Frances K; Davidson, Whitni B; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Yan, Lihan; Frey, Sharon E; Belshe, Robert B; Karem, Kevin L; Damon, Inger K

    2012-07-01

    Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

  11. The Spanish royal philanthropic expedition to bring smallpox vaccination to the New World and Asia in the 19th century.

    Science.gov (United States)

    Franco-Paredes, Carlos; Lammoglia, Lorena; Santos-Preciado, José Ignacio

    2005-11-01

    The New World was ravaged by smallpox for several centuries after the Spanish conquest. Jenner's discovery of the smallpox vaccine made possible the prevention and control of smallpox epidemics. In response to a large outbreak of smallpox in the Spanish colonies, King Charles IV appointed Francisco Xavier de Balmis to lead an expedition that would introduce Jenner's vaccine to these colonies. During the journey, the vaccine was kept viable by passing it from arm to arm in orphaned children, who were brought along expressly for that purpose and remained under the care of the orphanage's director. This expedition was the first large scale mass vaccination of its kind. The historic legacy of this pioneering event in international health should be revisited in the current era of persistent inequalities in global health.

  12. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    Directory of Open Access Journals (Sweden)

    Bonnie M Slike

    Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  13. Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    Stuart N. Isaacs

    2010-10-01

    Full Text Available Despite the eradication of smallpox several decades ago, variola and monkeypox viruses still have the potential to become significant threats to public health. The current licensed live vaccinia virus-based smallpox vaccine is extremely effective as a prophylactic vaccine to prevent orthopoxvirus infections, but because of safety issues, it is no longer given as a routine vaccine to the general population. In the event of serious human orthopoxvirus infections, it is important to have treatments available for individual patients as well as their close contacts. The smallpox vaccine and vaccinia immune globulin (VIG were used in the past as therapeutics for patients exposed to smallpox. VIG was also used in patients who were at high risk of developing complications from smallpox vaccination. Thus post-exposure vaccination and VIG treatments may again become important therapeutic modalities. This paper summarizes some of the historic use of the smallpox vaccine and immunoglobulins in the post-exposure setting in humans and reviews in detail the newer animal studies that address the use of therapeutic vaccines and immunoglobulins in orthopoxvirus infections as well as the development of new therapeutic monoclonal antibodies.

  14. In vitro efficacy of ST246 against smallpox and monkeypox.

    Science.gov (United States)

    Smith, Scott K; Olson, Victoria A; Karem, Kevin L; Jordan, Robert; Hruby, Dennis E; Damon, Inger K

    2009-03-01

    Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compound. ST-246 had 50% effective concentrations of

  15. [The real philanthropic expedition of the smallpox vaccine: monarchy and modernity in 1803].

    Science.gov (United States)

    Rigau-Pérez, José G

    2004-09-01

    Smallpox resulted in the death of 30 % of those who acquired it, so the preventive method discovered by Edward Jenner (London, 1798) spread very quickly. At the request in 1803 of Carlos IV, king of Spain, his government evaluated offers to carry smallpox vaccine to the colonies. The selected proposal, by doctor Francisco Xavier de Balmis, sought to take the lymph to America and Asia in a chain of arm to arm vaccination of foundlings. The Expedition set sail from Corunna on November 30, 1803, stopped in the Canary Isles, Puerto Rico, and Venezuela and after Caracas (1804) split in two groups. Balmis led some members of the Expedition to Cuba and Mexico. For the trip to the Philippines, in 1805, parents lent their children in exchange for economic compensation and the promise that the boys would be returned home. The Expedition returned to Mexico in August, 1807, but Balmis separately took vaccine to China and returned to Spain. Another contingent of the Expedition, under vice-director José Salvany, took vaccine to what we know as Colombia, Ecuador, Peru and Bolivia. His assistant Manuel Grajales reached the Chilean Patagonia in 1811. This article also comments on three principal themes - the institutional management of the scientific project, the conflicts that characterized its course, and the children's experience. The Vaccine Expedition was a brave and humanitarian endeavor, but also an extraordinary sanitary and administrative success. It was not until the twentieth century that a global eradication campaign eliminated smallpox in the world.

  16. ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense.

    Science.gov (United States)

    Monath, Thomas P; Caldwell, Joseph R; Mundt, Wolfgang; Fusco, Joan; Johnson, Casey S; Buller, Mark; Liu, Jian; Gardner, Bridget; Downing, Greg; Blum, Paul S; Kemp, Tracy; Nichols, Richard; Weltzin, Richard

    2004-10-01

    The threat of smallpox as a biological weapon has spurred efforts to create stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in animal skin (the original method), we cloned vaccinia virus (New York City Board of Health strain, Dryvax by plaque purification and amplified the clone in cell culture. The overarching goal was to produce a modern vaccine that was equivalent to the currently licensed Dryvax in its preclinical and clinical properties, and could thus reliably protect humans against smallpox. A variety of clones were evaluated, and many were unacceptably virulent in animal models. One clonal virus (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid cells. ACAM1000 was comparable to Dryvax in immunogenicity and protective activity but was less neurovirulent for mice and nonhuman primates. To meet requirements for large quantities of vaccine after the events of September 11th 2001, the ACAM1000 master virus seed was used to prepare vaccine (designated ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three Phase 1 clinical trials. The vaccines produced major cutaneous reactions and evoked neutralizing antibody and cell-mediated immune responses in the vast majority of subjects and had a reactogenicity profile similar to that of Dryvax.

  17. Immune responses to the smallpox vaccine given in combination with ST-246, a small-molecule inhibitor of poxvirus dissemination

    OpenAIRE

    Grosenbach, Douglas W.; Jordan, Robert; King, David S.; Berhanu, Aklile; Warren, Travis K.; Kirkwood-Watts, Dana L.; Tyavanagimatt, Shanthakumar; Tan, Ying; Wilson, Rebecca L.; Jones, Kevin F.; Hruby, Dennis E.

    2007-01-01

    The re-emerging threat of smallpox and the emerging threat of monkeypox highlight the need for effective poxvirus countermeasures. Currently approved smallpox vaccines have unacceptable safety profiles and, consequently, the general populace is no longer vaccinated, leading to an increasingly susceptible population. ST-246, a small-molecule inhibitor of poxvirus dissemination, has been demonstrated in various animal models to be safe and effective in preventing poxviral disease. This suggests...

  18. The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Jensen, Mette Lundsby

    2017-01-01

    : The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search......BACKGROUND: The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out...... globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. METHODS: We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea...

  19. Antiviral immunity following smallpox virus infection: a case-control study.

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W; Hanifin, Jon M; Mori, Motomi; Koudelka, Caroline W; Slifka, Mark K

    2010-12-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4(+) and CD8(+) T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases.

  20. Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study▿

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W.; Hanifin, Jon M.; Mori, Motomi; Koudelka, Caroline W.; Slifka, Mark K.

    2010-01-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4+ and CD8+ T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases. PMID:20926574

  1. Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

    Science.gov (United States)

    Bossi, Philippe; Tegnell, Anders; Baka, Agoritsa; Van Loock, Frank; Hendriks, J; Werner, Albrecht; Maidhof, Heinrich; Gouvras, Georgios

    2004-12-15

    Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

  2. Host range, growth property, and virulence of the smallpox vaccine: Vaccinia virus Tian Tan strain

    International Nuclear Information System (INIS)

    Fang Qing; Yang Lin; Zhu Weijun; Liu Li; Wang Haibo; Yu Wenbo; Xiao Genfu; Tien Po; Zhang Linqi; Chen Zhiwei

    2005-01-01

    Vaccinia Tian Tan (VTT) was used as a vaccine against smallpox in China for millions of people before 1980, yet the biological characteristics of the virus remain unclear. We have characterized VTT with respect to its host cell range, growth properties in vitro, and virulence in vivo. We found that 11 of the 12 mammalian cell lines studied are permissive to VTT infection whereas one, CHO-K1, is non-permissive. Using electron microscopy and sequence analysis, we found that the restriction of VTT replication in CHO-K1 is at a step before viral maturation probably due to the loss of the V025 gene. Moreover, VTT is significantly less virulent than vaccinia WR but remains neurovirulent in mice and causes significant body weight loss after intranasal inoculation. Our data demonstrate the need for further attenuation of VTT to serve either as a safer smallpox vaccine or as a live vaccine vector for other pathogens

  3. [Smallpox virus as biological weapon].

    Science.gov (United States)

    Kondrusik, Maciej; Hermanowska-Szpakowicz, Teresa

    2003-02-01

    Smallpox, because of its high case-fatality rate, easy transmission from human to human, lack of specific treatment represents nowadays one of the main threats in bioterrorist attacks. Over the centuries, naturally occurring smallpox with its case-fatality over 30 percent and its ability to spread in any climate and season has been treated as the most dangerous infectious disease. But it is now, 25 years after the last documented case of smallpox and cessation of routine vaccination in present mobile and susceptible population, smallpox virus spread might be rapid and devastating.

  4. A brief history of vaccines: smallpox to the present.

    Science.gov (United States)

    Hsu, Jennifer L

    2013-01-01

    Modern vaccine history began in the late 18th century with the discovery of smallpox immunization by Edward Jenner. This pivotal step led to substantial progress in prevention of infectious diseases with inactivated vaccines for multiple infectious diseases, including typhoid, plague and cholera. Each advance produced significant decreases in infection-associated morbidity and mortality, thus shaping our modem cultures. As knowledge of microbiology and immunology grew through the 20th century, techniques were developed for cell culture of viruses. This allowed for rapid advances in prevention of polio, varicella, influenza and others. Finally, recent research has led to development of alternative vaccine strategies through use of vectored antigens, pathogen subunits (purified proteins or polysaccharides) or genetically engineered antigens. As the science of vaccinology continues to rapidly evolve, knowledge of the past creates added emphasis on the importance of developing safe and effective strategies for infectious disease prevention in the 21st century.

  5. Risk of Inflammatory Bowel Disease following Bacille Calmette-Guérin and Smallpox Vaccination

    DEFF Research Database (Denmark)

    Villumsen, Anne Marie; Jess, Tine; Sørup, Signe

    2013-01-01

    Childhood immunology has been suggested to play a role in development of inflammatory bowel disease (IBD) based on the studies of childhood vaccinations, infections, and treatment with antibiotics. Bacille Calmette-Guérin (BCG) and smallpox vaccinations were gradually phased-out in Denmark...... for children born between 1965 and 1976, hence allowing the study of subsequent risk of Crohn's disease and ulcerative colitis in a unique prospective design....

  6. Immunomodulator-based enhancement of anti smallpox immune responses.

    Directory of Open Access Journals (Sweden)

    Osmarie Martínez

    Full Text Available The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists, and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

  7. Immunomodulator-based enhancement of anti smallpox immune responses.

    Science.gov (United States)

    Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L; Ríos-Olivares, Eddy; Otero, Miguel

    2015-01-01

    The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

  8. The rediscovery of smallpox.

    Science.gov (United States)

    Thèves, C; Biagini, P; Crubézy, E

    2014-03-01

    Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts--variolation, quarantine, and the isolation of infected subjects--until Jenner's discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  9. Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

    Science.gov (United States)

    Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L.; Ríos-Olivares, Eddy; Otero, Miguel

    2015-01-01

    Background The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. Methods We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. Results The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. Conclusion These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform. PMID:25875833

  10. Risks of serious complications and death from smallpox vaccination: A systematic review of the United States experience, 1963–1968

    Directory of Open Access Journals (Sweden)

    Aragón Tomás J

    2003-08-01

    Full Text Available Abstract Background The United States (US has re-instituted smallpox vaccinations to prepare for an intentional release of the smallpox virus into the civilian population. In an outbreak, people of all ages will be vaccinated. To prepare for the impact of large-scale ring and mass vaccinations, we conducted a systematic review of the complication and mortality risks of smallpox vaccination. We summarized these risks for post-vaccinial encephalitis, vaccinia necrosum (progressive vaccinia, eczema vaccinatum, generalized vaccinia, and accidental infection (inadvertant autoinoculation. Methods Using a MEDLINE search strategy, we identified 348 articles, of which seven studies met our inclusion criteria (the number of primary vaccinations and re-vaccinations were reported, sufficient data were provided to calculate complication or case-fatality risks, and comparable case definitions were used. For each complication, we estimated of the complication, death, and case-fatality risks. Results The life-threatening complications of post-vaccinial encephalitis and vaccinia necrosum were at least 3 and 1 per million primary vaccinations, respectively. Twenty-nine percent of vaccinees with post-vaccinial encephalitis died and 15% with vaccinia necrosum died. There were no deaths among vaccinees that developed eczema vaccinatum; however, 2.3% of non-vaccinated contacts with eczema vaccinatum died. Among re-vaccinees, the risk of post-vaccinial encephalitis was reduced 26-fold, the risk of generalized vaccinia was reduced 29-fold, and the risk of eczema vaccinatum was reduced 12-fold. However, the risk reductions of accidental infection and vaccinia necrosum were modest (3.8 and 1.5 fold respectively.

  11. High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.

    Science.gov (United States)

    Haralambieva, Iana H; Oberg, Ann L; Dhiman, Neelam; Ovsyannikova, Inna G; Kennedy, Richard B; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

    2012-11-15

    The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

  12. US Military Service Members Vaccinated Against Smallpox in 2003 and 2004 Experience a Slightly Higher Risk of Hospitalization Postvaccination

    Science.gov (United States)

    2008-01-01

    vaccination on the health of young adults . Published by Elsevier Ltd. 1. Introduction Through extensive vaccination efforts [1], smallpoxwas globally...Disorders of lipoid metabolism 74 0.1 17 0.0 2.43 1.42, 4.18 250 Diabetes mellitus 23 0.0 2 0.0 244 Acquired hypothyroidism 19 0.0 2 0.0 278 Obesity and...and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults . Vaccine 2006;24:6913–23. REPORT DOCUMENTATION

  13. The eradication of smallpox: organizational learning and innovation in international health administration.

    Science.gov (United States)

    Hopkins, J W

    1988-04-01

    The WHO smallpox eradication campaign represents perhaps the best example of a successful international health administration. In the 1st year of the campaign (1967), the guiding strategy was to vaccinate people en masse over a 2-3 year period in countries where smallpox was epidemic thereby conquering the disease. In Western Nigeria where 90% of the population had been vaccinated, a smallpox outbreak occurred in a religious sect resisting vaccinations and a delay in delivery of supplies forced a change in strategy. Campaign staff learned to rapidly isolate infected persons and swiftly vaccinate the uninfected in an outbreak area in order to break the transmission of smallpox, even where 1/2 the population had been vaccinated. Technological advancements also contributed to the campaign's success. For example, the jet injector vaccinated 1000 people/hour with efficient, reliable, mass produced potent, stable freeze dried vaccines (often produced in target countries) or the less costly and virtually maintenance free bifurcated needle was used. The most significant contribution to the success of the campaign, however, was the flexible mode of management adopted by the campaign staff at WHO which provided an appropriate environment for organizational learning and innovation. Although management was open and flexible, the campaign did depend on careful planning and setting of goals, continual assessment, and rapid response to field requests for assistance or advice. Trends in the incidence of smallpox was chosen as the indicator of success as opposed to the number of vaccinations. The campaign demonstrated the need for cultural adaptations as it operated in each country and region. This evaluation of the success of the smallpox campaign presents conclusions that serve as guidelines to the organization and administration of international programs designed to solve other health problems.

  14. The Smallpox Threat: The School Nurse's Role

    Science.gov (United States)

    Martin, Mary E.; Didion, Judy

    2003-01-01

    Today, with the threat of bioterrorism and war, there is a new dimension to the traditional role of the school nurse. The smallpox threat to public health will invoke the school nurse's role as an educator, liaison, and consultant in the community. This article discusses smallpox, the vaccination process, adverse effects, and postvaccination care.…

  15. Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

    Science.gov (United States)

    Molina, Chai; Earn, David J D

    2015-06-06

    Smallpox was eradicated in the 1970s, but new outbreaks could be seeded by bioterrorism or accidental release. Substantial vaccine-induced morbidity and mortality make pre-emptive mass vaccination controversial, and if vaccination is voluntary, then there is a conflict between self- and group interests. This conflict can be framed as a tragedy of the commons, in which herd immunity plays the role of the commons, and free-riding (i.e. not vaccinating pre-emptively) is analogous to exploiting the commons. This game has been analysed previously for a particular post-outbreak vaccination scenario. We consider several post-outbreak vaccination scenarios and compare the expected increase in mortality that results from voluntary versus imposed vaccination. Below a threshold level of post-outbreak vaccination effort, expected mortality is independent of the level of response effort. A lag between an outbreak starting and a response being initiated increases the post-outbreak vaccination effort necessary to reduce mortality. For some post-outbreak vaccination scenarios, even modest response lags make it impractical to reduce mortality by increasing post-outbreak vaccination effort. In such situations, if decreasing the response lag is impossible, the only practical way to reduce mortality is to make the vaccine safer (greater post-outbreak vaccination effort leads only to fewer people vaccinating pre-emptively). © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  16. Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence?

    Science.gov (United States)

    Olson, Victoria A.; Shchelkunov, Sergei N.

    2017-01-01

    Smallpox was the first human disease to be eradicated, through a concerted vaccination campaign led by the World Health Organization. Since its eradication, routine vaccination against smallpox has ceased, leaving the world population susceptible to disease caused by orthopoxviruses. In recent decades, reports of human disease from zoonotic orthopoxviruses have increased. Furthermore, multiple reports of newly identified poxviruses capable of causing human disease have occurred. These facts raise concerns regarding both the opportunity for these zoonotic orthopoxviruses to evolve and become a more severe public health issue, as well as the risk of Variola virus (the causative agent of smallpox) to be utilized as a bioterrorist weapon. The eradication of smallpox occurred prior to the development of the majority of modern virological and molecular biological techniques. Therefore, there is a considerable amount that is not understood regarding how this solely human pathogen interacts with its host. This paper briefly recounts the history and current status of diagnostic tools, vaccines, and anti-viral therapeutics for treatment of smallpox disease. The authors discuss the importance of further research to prepare the global community should a smallpox-like virus emerge.

  17. RESPONSE OF VOLTA CHILDREN TO JET INOCULATION OF COMBINED LIVE MEASLES, SMALLPOX AND YELLOW FEVER VACCINES.

    Science.gov (United States)

    MEYER, H M; HOSTETLER, D D; BERNHEIN, B C; ROGERS, N G; LAMBIN, P; CHASSARY, A; LABUSQUIERE, R; SMADEL, J E

    1964-01-01

    An earlier study established that Upper Volta children respond to vaccination with the Enders live attenuated measles strain in the same general fashion as do children in the USA. The present report describes a second pilot project carried out in Ouagadougou, Upper Volta. During this investigation various mixtures of live measles, smallpox and 17D yellow fever vaccines were introduced into susceptible infants by jet injection. Combining the attenuated virus vaccines did not alter or accentuate the characteristic clinical reactions elicited by the individual components, nor was there evidence of significant immunological interference. From this experience it is concluded that combined vaccination with these agents may be safely and effectively employed in larger programmes as the need dictates.

  18. Smallpox-Related Knowledge and Beliefs among Recent College Graduates

    Science.gov (United States)

    Bungum, Timothy; Day, Charlene

    2006-01-01

    Recent world events have increased concern and preparations for possible bioterror events. Despite worldwide efforts to limit access to bio-weapons, smallpox is still considered a potential bioterror threat. Americans' understanding of smallpox could prevent panic and enhance the willingness of citizens to receive vaccinations. Objective: The…

  19. Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial

    Science.gov (United States)

    Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A.; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2015-01-01

    Background. First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations. PMID:26380340

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

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    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.

  1. [Lessons learnt from the German smallpox outbreaks after World War II].

    Science.gov (United States)

    Sasse, Julia; Gelderblom, Hans R

    2015-07-01

    Even though smallpox was declared eradicated by WHO in 1980, it cannot be ruled out that the etiological variola virus could be used as a biological weapon. Undestroyed viruses from biowarfare programmes, virus strains left undetected in a freezer or dangerous recombinant poxvirus constructs could cause dangerous outbreaks in a relatively unprotected population. Despite an abundance of studies performed during the eradication of smallpox, epidemiological data for preparedness planning and outbreak control in modern, industrialized countries are scarce. Full-text hand search for the period from 1945 to 1975 in the main German public health journals. After World War II 12 smallpox outbreaks occurred in Germany. They were studied with the focus on the period of contagiousness, the protective effect of vaccination, booster-effect of revaccination and the place of infection. A total of 95 individuals contracted smallpox, including 10 fatalities. Despite having been previously vaccinated, 81 vaccinated persons came down with smallpox, yet 91% of them developed only mild symptoms. These patients presented a high risk for spreading the infection to contact persons due to misinterpretation of symptoms and the continuing social contacts. Basically, the risk of transmission in the first 2 to 3 days after onset of symptoms was low, thus facilitating antiepidemic measures. The importance of hospital preparedness is emphasized by the fact that most infections occurred in hospitals. The data analyzed provide valuable information for today's outbreak response planning and counter bioterrorism preparedness.

  2. A brief history of vaccines & vaccination in India

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    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.

  3. 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.

  4. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

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    Abdul Rivai

    2012-09-01

    Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

  5. Navigation and history of science: The smallpox Royal Expedition (Balmis and Salvany

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    Ignacio Jáuregui-Lobera

    2018-02-01

    Full Text Available By the end of 18th Century, smallpox killed about 400,000 citizens per year in Europe with a highest outbreak peak in 1796. This year, Edward Jenner discovered the smallpox vaccine and after being introduced in Spain, the King of Spain was asked to help American people against the disease. The transport of a fluid such delicate as the vaccine from a continent to another in extremely difficult sea voyages, which lasted several months, without electricity for keeping the cold chain, seemed impossible. Nevertheless Balmis and Salvany succeeded, by means of hundreds of orphans. Their bodies served as means of vaccine transport.

  6. Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

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    Clement A Meseda

    Full Text Available The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification. The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1 elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that

  7. Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

    Science.gov (United States)

    Meseda, Clement A; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P

    2016-01-01

    The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA

  8. Adverse Events Post Smallpox-Vaccination: Insights from Tail Scarification Infection in Mice with Vaccinia virus

    Science.gov (United States)

    Mota, Bruno E. F.; Gallardo-Romero, Nadia; Trindade, Giliane; Keckler, M. Shannon; Karem, Kevin; Carroll, Darin; Campos, Marco A.; Vieira, Leda Q.; da Fonseca, Flávio G.; Ferreira, Paulo C. P.; Bonjardim, Cláudio A.; Damon, Inger K.; Kroon, Erna G.

    2011-01-01

    Adverse events upon smallpox vaccination with fully-replicative strains of Vaccinia virus (VACV) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. The expansion of immune-suppressed populations and the possible release of Variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. Our goal was to evaluate the components of the host immune system that are sufficient to prevent morbidity/mortality in a murine model of tail scarification, which mimics immunological and clinical features of smallpox vaccination in humans. Infection of C57BL/6 wild-type mice led to a strictly localized infection, with complete viral clearance by day 28 p.i. On the other hand, infection of T and B-cell deficient mice (Rag1 −/−) produced a severe disease, with uncontrolled viral replication at the inoculation site and dissemination to internal organs. Infection of B-cell deficient animals (µMT) produced no mortality. However, viral clearance in µMT animals was delayed compared to WT animals, with detectable viral titers in tail and internal organs late in infection. Treatment of Rag1 −/− with rabbit hyperimmune anti-vaccinia serum had a subtle effect on the morbidity/mortality of this strain, but it was effective in reduce viral titers in ovaries. Finally, NUDE athymic mice showed a similar outcome of infection as Rag1 −/−, and passive transfer of WT T cells to Rag1 −/− animals proved fully effective in preventing morbidity/mortality. These results strongly suggest that both T and B cells are important in the immune response to primary VACV infection in mice, and that T-cells are required to control the infection at the inoculation site and providing help for B-cells to produce antibodies, which help to prevent viral dissemination. These insights might prove helpful to better identify

  9. SWOT analysis: strengths, weaknesses, opportunities and threats of the Israeli Smallpox Revaccination Program.

    Science.gov (United States)

    Huerta, Michael; Balicer, Ran D; Leventhal, Alex

    2003-01-01

    During September 2002, Israel began its current revaccination program against smallpox, targeting previously vaccinated "first responders" among medical and emergency workers. In order to identify the potential strengths and weaknesses of this program and the conditions under which critical decisions were reached, we conducted a SWOT analysis of the current Israeli revaccination program, designed to identify its intrinsic strengths and weaknesses, as well as opportunities for its success and threats against it. SWOT analysis--a practical tool for the study of public health policy decisions and the social and political contexts in which they are reached--revealed clear and substantial strengths and weaknesses of the current smallpox revaccination program, intrinsic to the vaccine itself. A number of threats were identified that may jeopardize the success of the current program, chief among them the appearance of severe complications of vaccination. Our finding of a lack of a generation of knowledge on smallpox vaccination highlights the need for improved physician education and dissipation of misconceptions that are prevalent in the public today.

  10. Genomic sequence and virulence of clonal isolates of vaccinia virus Tiantan, the Chinese smallpox vaccine strain.

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    Qicheng Zhang

    Full Text Available Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1 viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1 and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs. ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.

  11. Genomic sequence and virulence of clonal isolates of vaccinia virus Tiantan, the Chinese smallpox vaccine strain.

    Science.gov (United States)

    Zhang, Qicheng; Tian, Meijuan; Feng, Yi; Zhao, Kai; Xu, Jing; Liu, Ying; Shao, Yiming

    2013-01-01

    Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.

  12. Experiences with smallpox eradication in Ethiopia.

    Science.gov (United States)

    de Quadros, Ciro A

    2011-12-30

    The smallpox eradication campaign operated in Ethiopia from 1970 until 1977. During this time Ethiopia had only 84 hospitals, 64 health centres and fewer than 400 physicians in a country of 25 million people. In 1970 smallpox vaccination was relatively unknown in the country, and the government actually contested the fact that smallpox was present in the country. Most of the resources of the Ministry of Health were used for malaria eradication. Initial pessimism from the Ministry of Health and others was eventually overcome as the smallpox eradication campaign continued to pick up steam but many remained unenthusiastic. Ethiopia was the first country in the world to start its smallpox eradication campaign from day one with the strategy of "Surveillance and Containment". Establishing a surveillance system in a country with a limited health infrastructure was a daunting challenge. At the end of the first year of the programme in 1971, 26,000 cases of smallpox had been registered through the growing surveillance system. Throughout revolution of 1974 the smallpox campaign was the only UN program to operate in the country; in fact it expanded with the hire of many locals leading to a "nationalized" program. This development ushered in the most successful final phase of the program. As the program progressed cases were diminishing in most regions, however transmission continued in the Ogaden desert. Over the course of the campaign approximately 14.3 million US dollars was spent. Working conditions were extremely challenging and a variety of chiefs, guerrillas, landowners and governments had to be appeased. The programme was successful due to the dedicated national and international staff on the ground and by having the full support of the WHO HQ in Geneva. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Frequency of adverse events after vaccination with different vaccinia strains.

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    Mirjam Kretzschmar

    2006-08-01

    Full Text Available BACKGROUND: Large quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of vaccination-related adverse events, compared to the risk of contracting an infection. Although considerable effort has been made to understand the dynamics of smallpox transmission in modern societies, little attention has been paid to estimating the frequency of adverse events due to smallpox vaccination. Studies exploring the consequences of smallpox vaccination strategies have commonly used a frequency of approximately one death per million vaccinations, which is based on a study of vaccination with the New York City Board of Health (NYCBH strain of vaccinia virus. However, a multitude of historical studies of smallpox vaccination with other vaccinia strains suggest that there are strain-related differences in the frequency of adverse events after vaccination. Because many countries have stockpiled vaccine based on the Lister strain of vaccinia virus, a quantitative evaluation of the adverse effects of such vaccines is essential for emergency response planning. We conducted a systematic review and statistical analysis of historical data concerning vaccination against smallpox with different strains of vaccinia virus. METHODS AND FINDINGS: We analyzed historical vaccination data extracted from the literature. We extracted data on the frequency of postvaccinal encephalitis and death with respect to vaccinia strain and age of vaccinees. Using a hierarchical Bayesian approach for meta-analysis, we estimated the expected frequencies of postvaccinal encephalitis and death with respect to age at vaccination for smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large heterogeneity between findings from different studies and a time-period effect

  14. Licensed pertussis vaccines in the United States. History and current state.

    Science.gov (United States)

    Klein, Nicola P

    2014-01-01

    The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that waning protection following licensed acellular pertussis vaccines have been significant factors in the widespread reappearance of pertussis.

  15. Logistics in smallpox: the legacy.

    Science.gov (United States)

    Wickett, John; Carrasco, Peter

    2011-12-30

    Logistics, defined as "the time-related positioning of resources" was critical to the implementation of the smallpox eradication strategy of surveillance and containment. Logistical challenges in the smallpox programme included vaccine delivery, supplies, staffing, vehicle maintenance, and financing. Ensuring mobility was essential as health workers had to travel to outbreaks to contain them. Three examples illustrate a range of logistic challenges which required imagination and innovation. Standard price lists were developed to expedite vehicle maintenance and repair in Bihar, India. Innovative staffing ensured an adequate infrastructure for vehicle maintenance in Bangladesh. The use of disaster relief mechanisms in Somalia provided airlifts, vehicles and funding within 27 days of their initiation. In contrast the Expanded Programme on Immunization (EPI) faces more complex logistical challenges. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine.

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    Brett A McKinney

    Full Text Available Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA, which has been implicated in a previous epistasis network analysis of smallpox vaccine.

  17. Frequency of Adverse Events after Vaccination with Different Vaccinia Strains.

    NARCIS (Netherlands)

    Kretzschmar, Mirjam; Wallinga, Jacco; Teunis, Peter F M; Xing, Shuqin; Mikolajczyk, Rafael

    2006-01-01

    BACKGROUND: Large quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of

  18. Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).

    Science.gov (United States)

    Mucker, Eric M; Goff, Arthur J; Shamblin, Joshua D; Grosenbach, Douglas W; Damon, Inger K; Mehal, Jason M; Holman, Robert C; Carroll, Darin; Gallardo, Nadia; Olson, Victoria A; Clemmons, Cody J; Hudson, Paul; Hruby, Dennis E

    2013-12-01

    Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 10(8) PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo

  19. Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

    Science.gov (United States)

    Osheroff, Neil

    2006-10-01

    Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.

  20. 17th Century Variola Virus Reveals the Recent History of Smallpox.

    Science.gov (United States)

    Duggan, Ana T; Perdomo, Maria F; Piombino-Mascali, Dario; Marciniak, Stephanie; Poinar, Debi; Emery, Matthew V; Buchmann, Jan P; Duchêne, Sebastian; Jankauskas, Rimantas; Humphreys, Margaret; Golding, G Brian; Southon, John; Devault, Alison; Rouillard, Jean-Marie; Sahl, Jason W; Dutour, Olivier; Hedman, Klaus; Sajantila, Antti; Smith, Geoffrey L; Holmes, Edward C; Poinar, Hendrik N

    2016-12-19

    Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4-6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone. To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics [1, 2, 10]. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20 th century VARVs, indicating that such loss of gene function had occurred before ca. 1650. Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18 th and 19 th centuries, concomitant with the development of modern vaccination. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. [Strategies, actors, promises and fears in the smallpox vaccinations campaigns in Mexico: from the Porfiriato to the Post-revolution (1880-1940)].

    Science.gov (United States)

    Agostoni, Claudia

    2011-02-01

    The article examines some of the strategies employed by the Mexican health authorities that led to the organization of massive and obligatory smallpox vaccination campaigns from the late 1880s to the 1940s, a period of Mexican history that corresponds to the Porfirio Díaz regime (1877-1911), to the armed phase of the Mexican Revolution (1910-1920), and to the first two decades of the Post-revolutionary governments (1920-1940). Attention will be placed of the vaccination programs in the main urban settings, notably in Mexico City, as well as the gradual but decisive organization and regulation of vaccination campaigns in the heterogeneous rural milieu. Furthermore, the importance that hygienic education acquired will be explored, as well as the divergent and contested responses that emerged due to the obligatory vaccination campaigns, responses that included resistance, fear, uncertainty and widespread acceptance.

  2. Smallpox

    Science.gov (United States)

    ... smallpox could someday be used as a biological warfare agent. No cure or treatment for smallpox exists. ... logo are trademarks of Mayo Foundation for Medical Education and Research. © 1998-2018 Mayo Foundation for Medical ...

  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. GM-CSF production allows the identification of immunoprevalent antigens recognized by human CD4+ T cells following smallpox vaccination.

    Directory of Open Access Journals (Sweden)

    Valeria Judkowski

    Full Text Available The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a "T cell-driven" methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens.

  5. Signs and Symptoms (Smallpox)

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Smallpox Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Smallpox About Smallpox History of Smallpox Spread and Eradication ...

  6. Extracting key information from historical data to quantify the transmission dynamics of smallpox

    Directory of Open Access Journals (Sweden)

    Brockmann Stefan O

    2008-08-01

    Full Text Available Abstract Background Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data. Main findings First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1 The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2 The highest frequency (61.8% of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3 The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions. Conclusion Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.

  7. Licensed pertussis vaccines in the United States: History and current state

    OpenAIRE

    Klein, Nicola P

    2014-01-01

    The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that w...

  8. 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.

  9. Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

    Science.gov (United States)

    Volz, A; Sutter, G

    2017-01-01

    Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

  10. The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines.

    Science.gov (United States)

    Marcos, Erica; Zhao, Bin; He, Yongqun

    2013-11-26

    Licensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO). Like OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term 'human vaccinee population' is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed. The ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents

  11. History of Smallpox and Its Spread in Human Populations.

    Science.gov (United States)

    Thèves, Catherine; Crubézy, Eric; Biagini, Philippe

    2016-08-01

    Smallpox is considered among the most devastating of human diseases. Its spread in populations, initiated for thousands of years following a probable transmission from an animal host, was concomitant with movements of people across regions and continents, trade and wars. Literature permitted to retrace the occurrence of epidemics from ancient times to recent human history, smallpox having affected all levels of past society including famous monarchs. The disease was officially declared eradicated in 1979 following intensive vaccination campaigns.Paleomicrobiology dedicated to variola virus is restricted to few studies, most unsuccessful, involving ancient material. Only one recent approach allowed the identification of viral DNA fragments from lung tissue of a 300-year-old body excavated from permafrost in Eastern Siberia; phylogenetic analysis revealed that this ancient strain was distinct from those described during the 20th century.

  12. Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

    Science.gov (United States)

    Golden, Joseph W; Josleyn, Matthew; Mucker, Eric M; Hung, Chien-Fu; Loudon, Peter T; Wu, T C; Hooper, Jay W

    2012-01-01

    Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

  13. Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Joseph W Golden

    Full Text Available Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA. We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV nonhuman primate (NHP challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

  14. Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

    Science.gov (United States)

    Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

    2012-01-01

    Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

  15. Smallpox: can we still learn from the journey to eradication?

    Science.gov (United States)

    Smith, Kendall A

    2013-05-01

    One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe.

  16. Mozart and smallpox

    NARCIS (Netherlands)

    Zegers, Richard H. C.

    2007-01-01

    In 1767 at 11 years of age, composer Wolfgang Amadeus Mozart contracted smallpox, allegedly causing him temporary blindness. Although now eradicated, smallpox in those days had a high mortality rate, and the history of classical music would have been very different if Mozart had become permanently

  17. L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines

    OpenAIRE

    Pacchioni, Sole Maria; Bissa, Massimiliano; Zanotto, Carlo; Morghen, Carlo De Giuli; Illiano, Elena; Radaelli, Antonia

    2013-01-01

    Background The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most e...

  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. Frequently Asked Questions and Answers on Smallpox

    Science.gov (United States)

    ... with smallpox is still infectious until the last scabs fall off. How fast does smallpox spread? The ... Variola virus research Variola virus repository inspections Synthetic Biology Technology for smallpox Post-eradication of smallpox You ...

  20. Concomitant use of an oral live pentavalent human-bovine reassortant rotavirus vaccine with licensed parenteral pediatric vaccines in the United States.

    Science.gov (United States)

    Rodriguez, Zoe M; Goveia, Michelle G; Stek, Jon E; Dallas, Michael J; Boslego, John W; DiNubile, Mark J; Heaton, Penny M

    2007-03-01

    A live pentavalent rotavirus vaccine (PRV) containing 5 human-bovine (WC3) reassortants expressing human serotypes G1, G2, G3, G4 and P1A[8] was evaluated in a blinded, placebo-controlled study. Possible interactions between PRV and concomitantly administered licensed pediatric vaccines were investigated in a United States-based nested substudy (Concomitant Use Study) of the Rotavirus Efficacy and Safety Trial. From 2002 to 2003, healthy infants approximately 6 to 12 weeks of age at entry were randomized to receive either 3 oral doses of PRV or placebo at 4- to 10-week intervals. Subjects were also to receive combined Haemophilus influenzae type b and hepatitis B vaccine (2 doses), diphtheria and tetanus toxoids and acellular pertussis vaccine (3 doses), inactivated poliovirus vaccine (2 doses) and pneumococcal conjugate vaccine (3 doses) on the same day; oral poliovirus vaccine was not administered. Immunogenicity was assessed by measuring antibody responses to PRV and antigens contained in the licensed vaccines. Cases of rotavirus gastroenteritis were defined by forceful vomiting and/or -3 watery or looser-than-normal stools within a 24-hour period, and detection of rotavirus antigen in the stool. Safety was assessed by reporting of adverse events using diary cards. The Concomitant Use Study enrolled 662 subjects in the PRV group and 696 subjects in the placebo group. For the 17 antigens in the concomitantly administered vaccines, antibody responses were similar in PRV and placebo recipients, except for moderately diminished antibody responses to the pertactin component of pertussis vaccine. Efficacy of PRV against rotavirus gastroenteritis of any severity was 89.5% (95% CI = 26.5-99.8%). PRV was generally well tolerated when given concomitantly with the prespecified vaccines. In this study, antibody responses to the concomitantly administered vaccines were generally similar in PRV and placebo recipients. PRV was efficacious and well tolerated when given

  1. Mozart and smallpox.

    Science.gov (United States)

    Zegers, Richard H C

    2007-01-01

    In 1767 at 11 years of age, composer Wolfgang Amadeus Mozart contracted smallpox, allegedly causing him temporary blindness. Although now eradicated, smallpox in those days had a high mortality rate, and the history of classical music would have been very different if Mozart had become permanently blind, or died, as a result of the disease.

  2. The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Jensen, Mette Lundsby

    2017-01-01

    -Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression. RESULTS: Bacillus......: The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search...

  3. 76 FR 79203 - Prospective Grant of Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines

    Science.gov (United States)

    2011-12-21

    ... Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines AGENCY: National Institutes....7. The invention relates to compositions and methods of use as Veterinary Influenza Vaccines... to humans. This technology describes DNA vaccines against influenza serotypes H5N1, H1N1, H3N2, and...

  4. Ontology-Based Vaccine Adverse Event Representation and Analysis.

    Science.gov (United States)

    Xie, Jiangan; He, Yongqun

    2017-01-01

    Vaccine is the one of the greatest inventions of modern medicine that has contributed most to the relief of human misery and the exciting increase in life expectancy. In 1796, an English country physician, Edward Jenner, discovered that inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide, we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine 29:D7-D9, 2011). Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication (Bonanni, Vaccine 17:S120-S125, 1999).Although vaccine development and administration are tremendously successful and cost-effective practices to human health, no vaccine is 100% safe for everyone because each person reacts to vaccinations differently given different genetic background and health conditions. Although all licensed vaccines are generally safe for the majority of people, vaccinees may still suffer adverse events (AEs) in reaction to various vaccines, some of which can be serious or even fatal (Haber et al., Drug Saf 32(4):309-323, 2009). Hence, the double-edged sword of vaccination remains a concern.To support integrative AE data collection and analysis, it is critical to adopt an AE normalization strategy. In the past decades, different controlled terminologies, including the Medical Dictionary for Regulatory Activities (MedDRA) (Brown EG, Wood L, Wood S, et al., Drug Saf 20(2):109-117, 1999), the Common Terminology Criteria for Adverse Events (CTCAE) (NCI, The Common Terminology Criteria for Adverse Events (CTCAE). Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html . Access on 7 Oct 2015), and the World Health Organization (WHO) Adverse Reactions Terminology (WHO-ART) (WHO, The WHO Adverse Reaction Terminology - WHO-ART. Available from: https://www.umc-products.com/graphics/28010.pdf

  5. Smallpox: An eradicated infection with persistent sequels - Case report and a brief on smallpox

    International Nuclear Information System (INIS)

    Jastaneiah, Sabah

    2009-01-01

    Sequelae of smallpox infection on the ocular surface are still seen, including corneal scars adherent leukoma and phthisical globes. This paper will report another sequel of smallpox infection causing inadvertent bleb in a 62-year-old diabetic female with no history of ocular surgery or trauma in either eye. The patient had smallpox infection during her childhood. Her follow up extended from May 1997 until August 2007 with a constant eye examinations including controlled intraocular pressure, avascular cystic inadvertent bleb, and up drown peaked pupil. (author)

  6. Vaccines licensed and in clinical trials for the prevention of dengue.

    Science.gov (United States)

    Torresi, J; Ebert, G; Pellegrini, M

    2017-05-04

    Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.

  7. The prevention and eradication of smallpox: a commentary on Sloane (1755) ‘An account of inoculation’

    Science.gov (United States)

    Weiss, Robin A.; Esparza, José

    2015-01-01

    Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called ‘variolation’) involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox (‘vaccination’) followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these ‘weapons of mass protection’. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. PMID:25750241

  8. Planning for smallpox outbreaks

    Science.gov (United States)

    Ferguson, Neil M.; Keeling, Matt J.; John Edmunds, W.; Gani, Raymond; Grenfell, Bryan T.; Anderson, Roy M.; Leach, Steve

    2003-10-01

    Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979. We review the use of models in smallpox planning within the broader epidemiological context set by recent outbreaks of both novel and re-emerging pathogens.

  9. 76 FR 79203 - Prospective Grant of Exclusive License: Avian Influenza Vaccines for Domesticated Poultry/Wild...

    Science.gov (United States)

    2011-12-21

    ... Exclusive License: Avian Influenza Vaccines for Domesticated Poultry/Wild Birds To Be Provided to the... serotypes H5N1, H1N1, H3N2, and H3N8 for poultry, swine and equine. Particularly one vaccine, a trivalent... influenza vaccines are specifically designed for poultry, swine and equine recipients, with the following...

  10. Smallpox

    Science.gov (United States)

    ... two research laboratories in Atlanta, Georgia, and in Russia. Why Is the Study of Smallpox a Priority ... products; and establish platforms that can reduce the time and cost of creating new products. This is ...

  11. Smallpox

    Science.gov (United States)

    ... infection caused by the variola virus. For centuries, epidemics affected people all over the globe, and the ... these stored virus samples with the aim of spreading smallpox infection. Despite talk about the possibility of ...

  12. Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

    Science.gov (United States)

    Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng

    2018-02-14

    The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

  13. Small(pox) success?

    Science.gov (United States)

    Birn, Anne-Emanuelle

    2011-02-01

    The 30th anniversary of the World Health Organization's (WHO) official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata) became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.

  14. Small(pox success?

    Directory of Open Access Journals (Sweden)

    Anne-Emanuelle Birn

    Full Text Available The 30th anniversary of the World Health Organization's (WHO official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.

  15. Metabolites as Biomarkers of Adverse Reactions Following Vaccination: A Pilot Study using Nuclear Magnetic Resonance Metabolomics

    Science.gov (United States)

    McClenathan, Bruce M.; Stewart, Delisha A.; Spooner, Christina E.; Pathmasiri, Wimal W.; Burgess, Jason P.; McRitchie, Susan L.; Choi, Y. Sammy; Sumner, Susan C.J.

    2017-01-01

    An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers. PMID:28169076

  16. Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico´s Universal Vaccination Program

    Directory of Open Access Journals (Sweden)

    Mauricio Hernández-Ávila

    2016-01-01

    Full Text Available Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a adequate vaccine efficacy against dengue virus (DENV infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant

  17. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960 Outra vacina, outra história: a vacinação de BCG contra tuberculose na Índia, 1948 a 1960

    Directory of Open Access Journals (Sweden)

    Niels Brimnes

    2011-02-01

    Full Text Available Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.Através da observação da vacinação em massa de BCG contra a tuberculose na Índia durante os anos de 1948 a 1960, este artigo chama a atenção para a diversidade da história da vacinação. As características das campanhas de vacinação geralmente diferem daquelas celebradas nas campanhas para erradicação da varíola. Devido às diferenças entre a varíola e a turberculose, assim como entre as vacinas desenvolvidas para combater essas doenças, uma análise da vacinação em massa de BCG contra a turberculose parece especialmente bem situada para essa proposta. Três pontos de diferença foram identificados. O primeiro é que em contextos não ocidentais os procedimentos da vacinação de BCG foram modificados em uma extensão maior do que a vacinação contra a varíola. Em segundo lugar, a tuberculose não tinha o drama e a urgência da varíola, e as campanhas de vacinação de BCG

  18. The Royal Philanthropic Expedition of the Vaccine: a landmark in the history of public health.

    Science.gov (United States)

    Soto-Pérez-de-Celis, E

    2008-11-01

    In 1979, smallpox officially became the first disease ever to be eradicated by mankind. The global efforts to defeat this dreadful pandemic, however, started almost two centuries before. One of the most important, and sometimes forgotten, events in the fight against smallpox was the Royal Philanthropic Expedition of the Vaccine, commissioned by Charles IV of Spain to physicians Francisco Xavier Balmis y Berenguer and Jose Salvany in 1804. The aim of this expedition was to take the smallpox vaccine, discovered by Jenner, to Spain's territories in the Americas and in the Far East. After several years of vaccination in modern day Puerto Rico, Cuba, Venezuela, Ecuador, Peru, Bolivia, Chile, Mexico and the Philippines, the expedition returned to Europe. To this day, the Balmis and Salvany expedition remains a great example of international cooperation, and a landmark in the history of public health.

  19. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

    2016-01-01

    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore...

  20. Vaccination and Clinical Severity: Is the Effectiveness of Contact Tracing and Case Isolation Hampered by Past Vaccination?

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    2013-02-01

    Full Text Available While contact tracing and case isolation are considered as the first choice of interventions against a smallpox bioterrorist event, their effectiveness under vaccination is questioned, because not only susceptibility of host and infectiousness of case but also the risk of severe clinical manifestations among cases is known to be reduced by vaccine-induced immunity, thereby potentially delaying the diagnosis and increasing mobility among vaccinated cases. We employed a multi-type stochastic epidemic model, aiming to assess the feasibility of contact tracing and case isolation in a partially vaccinated population and identify data gaps. We computed four epidemiological outcome measures, i.e., (i the threshold of a major epidemic under the interventions; (ii the expected total number of cases; (iii the probability of extinction, and (iv the expected duration of an outbreak, demonstrating that all of these outcomes critically depend on the clinical impact of past vaccination on the diagnosis and movement of vaccinated cases. We discuss that, even in the absence of smallpox in the present day, one should consider the way to empirically quantify the delay in case detection and an increase in the frequency of contacts among previously vaccinated cases compared to unvaccinated during the early stage of an epidemic so that the feasibility of contact tracing and case isolation in a vaccinated population can be explicitly assessed.

  1. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects.

    Science.gov (United States)

    Greenberg, Richard N; Hay, Christine M; Stapleton, Jack T; Marbury, Thomas C; Wagner, Eva; Kreitmeir, Eva; Röesch, Siegfried; von Krempelhuber, Alfred; Young, Philip; Nichols, Richard; Meyer, Thomas P; Schmidt, Darja; Weigl, Josef; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2016-01-01

    Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group

  2. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis.

    Directory of Open Access Journals (Sweden)

    Richard N Greenberg

    Full Text Available Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD. Prior studies evaluating Modified Vaccinia Ankara virus (MVA, a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30 and 282 healthy subjects.Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.ClinicalTrials.gov NCT00316602.

  3. Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

    Science.gov (United States)

    Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

    2010-10-01

    This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. [Should the human smallpox virus (variola) be destroyed?].

    Science.gov (United States)

    Tryland, Morten

    2004-10-21

    Smallpox, caused by variola virus, was a terror for civilizations around the world for more than 3000 years. Although the disease is eradicated, hundreds of variola virus isolates are kept in two WHO-collaborating facilities, one in USA and one in Russia. In spite of several agreements on destruction, it is now doubtful that these virus isolates will be destroyed. Variola virus may exist in other places and may be used as a biological weapon in war or for terror. Further research on variola virus is thus essential in order to achieve a better understanding of the pathogenicity of the virus and to develop new anti-variola virus vaccines and antiviral drugs.

  5. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    Science.gov (United States)

    Aguiar, Maíra; Stollenwerk, Nico; Halstead, Scott B

    2016-12-01

    With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia), was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9-16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy) was noted for children younger than 9 years of age. Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE). An age structured model was developed based on Sanofi's recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1) Vaccinate 4 or 20% of individuals, ages 9-45 years, seropositives and seronegatives, and 2) vaccinate 4 or 20% of individuals, ages 9-45 years, who are dengue immune only. Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably.

  6. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    Directory of Open Access Journals (Sweden)

    Maíra Aguiar

    2016-12-01

    Full Text Available With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia, was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9-16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy was noted for children younger than 9 years of age.Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE. An age structured model was developed based on Sanofi's recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1 Vaccinate 4 or 20% of individuals, ages 9-45 years, seropositives and seronegatives, and 2 vaccinate 4 or 20% of individuals, ages 9-45 years, who are dengue immune only.Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably.

  7. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    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

  8. The Emergency campaign for smallpox eradication from Somalia (1977-1979)--revisited.

    Science.gov (United States)

    Deria, Abdullahi

    2011-12-30

    The historical significance of smallpox eradication from Somalia lies in the fact that the country was the last to record the last endemic smallpox case in the world. Before 1977 the programme was mismanaged. In the mid-1970s, the programme was plagued with concealment. Confirmation of smallpox outbreak in Mogadishu in September 1976 delayed global smallpox eradication. The Government maintained that there was no ongoing smallpox transmission in the country after the Mogadishu outbreak and frustrated independent attempts to verify its claim. In February 1977 the Government allowed World Health Organization (WHO) epidemiologists to search, unhindered, for smallpox outside Mogadishu. Soon widespread smallpox transmission was detected. The Government appealed for international support. The strategy to stop the smallpox transmission was based on surveillance and containment. The WHO took the leading role of the campaign which, in spite of the Somalia/Ethiopia war of 1977/78, culminated in the eradication of smallpox from the country. Somalia was certified smallpox-free on 19 October 1979. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. The De Novo Synthesis of Horsepox Virus: Implications for Biosecurity and Recommendations for Preventing the Reemergence of Smallpox.

    Science.gov (United States)

    Koblentz, Gregory D

    In March 2017, the American biotech company Tonix announced that a Canadian scientist had synthesized horsepox virus as part of a project to develop a safer vaccine against smallpox. The first de novo synthesis of an orthopoxvirus, a closely related group of viruses that includes horsepox and the variola virus that causes smallpox, crosses an important Rubicon in the field of biosecurity. The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security. That threat has been held at bay for the past 40 years by the extreme difficulty of obtaining variola virus and the availability of effective medical countermeasures. The techniques demonstrated by the synthesis of horsepox have the potential to erase both of these barriers. The primary risk posed by this research is that it will open the door to the routine and widespread synthesis of other orthopoxviruses, such as vaccinia, for use in research, public health, and medicine. The normalization and globalization of orthopoxvirus synthesis for these beneficial applications will create a cadre of laboratories and scientists that will also have the capability and expertise to create infectious variola virus from synthetic DNA. Unless the safeguards against the synthesis of variola virus are strengthened, the capability to reintroduce smallpox into the human population will be globally distributed and either loosely or completely unregulated, providing the foundation for a disgruntled or radicalized scientist, sophisticated terrorist group, unscrupulous company, or rogue state to recreate one of humanity's most feared microbial enemies. The reemergence of smallpox-because of a laboratory accident or an intentional release-would be a global health disaster. International organizations, national governments, the DNA synthesis industry, and the synthetic biology community all have a role to play in devising new approaches to preventing the reemergence of

  10. MHC-I-restricted epitopes conserved among variola and other related orthopoxviruses are recognized by T cells 30 years after vaccination

    DEFF Research Database (Denmark)

    Tang, Sheila Tuyet; Wang, M.; Lamberth, K.

    2008-01-01

    It is many years since the general population has been vaccinated against smallpox virus. Here, we report that human leukocyte antigen (HLA) class I restricted T cell epitopes can be recognized more than 30 years after vaccination. Using bioinformatic methods, we predicted 177 potential cytotoxic T...... lymphocyte epitopes. Eight epitopes were confirmed to stimulate IFN-gamma release by T cells in smallpox-vaccinated subjects. The epitopes were restricted by five supertypes (HLA-A1, -A2, -A24 -A26 and -B44). Significant T cell responses were detected against 8 of 45 peptides with an HLA class I affinity...... of K(D) less than or equal to 5 nM, whereas no T cell responses were detected against 60 peptides with an HLA affinity of K(D) more than 5 nM. All epitopes were fully conserved in seven variola, vaccinia and cowpox strains. Knowledge of the long-term response to smallpox vaccination may lead...

  11. 75 FR 6211 - Prospective Grant of Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine...

    Science.gov (United States)

    2010-02-08

    ... Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1,2,3, and 4 AGENCY: National Institutes of Health, Public Health...., ``Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses''-- European Patent...

  12. Live attenuated vaccines: Historical successes and current challenges

    Energy Technology Data Exchange (ETDEWEB)

    Minor, Philip D., E-mail: Philip.Minor@nibsc.org

    2015-05-15

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.

  13. Live attenuated vaccines: Historical successes and current challenges

    International Nuclear Information System (INIS)

    Minor, Philip D.

    2015-01-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues

  14. [History of Smallpox Vaccination and of the Vaccine Supply in Hungary, up to 1890].

    Science.gov (United States)

    Kiss, László

    2015-01-01

    One of the preconditions for the spread of vaccination against pox diseases was making vaccination available. The first vaccinations were carried out using original cowpox lymph sent by Jenner. For further vaccinations the vaccine was extracted from the blisters of those who had been successfully inoculated. In order to provide vaccine continuously six vaccine centres were set up in 1804 in the following cities: Pest, Buda, Kassa, Gyula, Pozsony and Zágráb (Croatia). Detailed information is available only about the centre in Pest which operated in Rókus Hospital under the leadership of the hospital director András Bossányi. Besides regular vaccination they also provided vaccine for the countryside. From 1824 the vaccine was relocated to the medical faculty of the university in Pest and Ferenc Gebhardt, an instructor of surgeons, became its head. The centre operated in the building of the medical faculty and vaccinations were given on Thursdays and Sundays. After the retirement of Gebhardt in 1860, the centre was taken over by the dermatologist Ferenc Poor for a short time, then by Ignác Semmelweis. From 1863 Gergely Patrubány was responsible for managing the centre. In 1874 the central vaccine institution moved to the Hospital for Poor Children in Pest where it was led first by Lázár Wittman, then by Géza Hainiss. In the 1880s private institutions appeared, the best known were Dani Pécsi's centre in Pest and Béla Intze's one in Tirgu Lapus (Romania). Between 1873 an 1889 András Kreichel ran a vaccine centre in Nálepkovo (Slovakia).

  15. Smallpox: A Review for Health Educators

    Science.gov (United States)

    Bungum, Timothy J.

    2003-01-01

    Since the declaration of the eradication of smallpox in May of 1980 concern about this virus has ebbed. However, recent world events, including the destabilization of governments, have raised concerns that smallpox could fall into the hands of nefarious individuals or groups who might attempt to use the virus as a weapon. In Centers for Disease…

  16. From smallpox eradication to contemporary global health initiatives: enhancing human capacity towards a global public health goal.

    Science.gov (United States)

    Tarantola, Daniel; Foster, Stanley O

    2011-12-30

    The eradication of smallpox owes its success first and foremost to the thousands of lay health workers and community members who, throughout the campaign and across continents, took on the roles of advocates, educators, vaccinators, care providers and contributors to epidemic surveillance and containment. Bangladesh provides a good example where smallpox eradication and the capacity enhancement needed to achieve this goal resulted in a two-way mutually beneficial process. Smallpox-dedicated staff provided community members with information guidance, support and tools. In turn, communities not only created the enabling environment for smallpox program staff to perform their work but acquired the capacity to perform essential eradication tasks. Contemporary global health programmes can learn much from these core lessons including: the pivotal importance of supporting community aspirations, capacity and resilience; the critical need to enhance commitment, capacity and accountability across the workforce; and the high value of attentive human resources management and support. We owe to subsequent global disease control, elimination and eradication ventures recognition of the need for social and behavioural science to inform public health strategies; the essential roles that civil society organizations and public-private partnerships can play in public health discourse and action; the overall necessity of investing in broad-based health system strengthening; and the utility of applying human rights principles, norms and standards to public health policy and practice. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  17. A Global Perspective on Vaccine Safety and Public Health: The Global Advisory Committee on Vaccine Safety

    Science.gov (United States)

    Folb, Peter I.; Bernatowska, Ewa; Chen, Robert; Clemens, John; Dodoo, Alex N. O.; Ellenberg, Susan S.; Farrington, C. Patrick; John, T. Jacob; Lambert, Paul-Henri; MacDonald, Noni E.; Miller, Elizabeth; Salisbury, David; Schmitt, Heinz-J.; Siegrist, Claire-Anne; Wimalaratne, Omala

    2004-01-01

    Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles–mumps–rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines. PMID:15514229

  18. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    OpenAIRE

    Maíra Aguiar; Nico Stollenwerk; Scott B Halstead

    2016-01-01

    Background With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteu...

  19. On the origin of smallpox: correlating variola phylogenics with historical smallpox records.

    Science.gov (United States)

    Li, Yu; Carroll, Darin S; Gardner, Shea N; Walsh, Matthew C; Vitalis, Elizabeth A; Damon, Inger K

    2007-10-02

    Human disease likely attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for >2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because VARV has a large, slowly evolving DNA genome, we were able to construct a robust phylogeny of VARV by analyzing concatenated single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. Our results show two primary VARV clades, which likely diverged from an ancestral African rodent-borne variola-like virus either approximately 16,000 or approximately 68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. Another primary clade included both alastrim minor, a phenotypically mild smallpox described from the American continents, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP, and then further diverged into two subclades at least 800 YBP. All of these analyses indicate that the divergence of alastrim and variola major occurred earlier than previously believed.

  20. Spinocellulært karcinom opstået ved cikatrice efter Calmette-vaccination

    DEFF Research Database (Denmark)

    Nielsen, Rikke Maria; Andersen, F.; Salskov-Iversen, Maria Luise

    2014-01-01

    Marjolin's ulcer is an aggressive squamous cell carcinoma (SCC) found in chronically inflamed skin. SCC has been reported in smallpox vaccination sites, whereas basal cell carcinomas are more common in scar after bacille Calmette-Guerin (BCG) vaccination. A 72-year-old man presented with a chronic...

  1. Safety of licensed vaccines in HIV-infected persons: a systematic review protocol

    Science.gov (United States)

    2014-01-01

    Background Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. Methods/Design We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Discussion Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be

  2. Biopower, Normalization, and HPV: A Foucauldian Analysis of the HPV Vaccine Controversy.

    Science.gov (United States)

    Engels, Kimberly S

    2016-09-01

    This article utilizes the Foucauldian concepts of biopower and normalization to give an analysis of the debate surrounding the controversial administration of the HPV vaccine to adolescents. My intention is not to solve the problem, rather to utilize a Foucauldian framework to bring various facets of the issue to light, specifically the way the vaccine contributes to strategies of power in reference to how young adults develop within relationships of power. To begin, the article provides an overview of the Foucauldian concepts of biopower and normalization, including how these two strategies of power were present in the administration of the smallpox vaccine in the 19th century. Next, information about HPV and the history of the current controversy in the United States is presented. Lastly, the article presents an analysis of the strategies of biopower and normalization present in the debate on HPV, including an emphasis on how the vaccination is similar to, and different from, 19th century smallpox vaccination. It also explores the way that mechanisms of disease control affect and are affected by individual subjects, in this case, adolescents.

  3. A meningococcal NOMV-FHbp vaccine for Africa elicits broader serum bactericidal antibody responses against serogroup B and non-B strains than a licensed serogroup B vaccine.

    Science.gov (United States)

    Pajon, Rolando; Lujan, Eduardo; Granoff, Dan M

    2016-01-27

    Meningococcal epidemics in Sub-Sahara caused by serogroup A strains are controlled by a group A polysaccharide conjugate vaccine. Strains with serogroups C, W and X continue to cause epidemics. Protein antigens in licensed serogroup B vaccines are shared among serogroup B and non-B strains. Compare serum bactericidal antibody responses elicited by an investigational native outer membrane vesicle vaccine with over-expressed Factor H binding protein (NOMV-FHbp) and a licensed serogroup B vaccine (MenB-4C) against African serogroup A, B, C, W and X strains. Human Factor H (FH) transgenic mice were immunized with NOMV-FHbp prepared from a mutant African meningococcal strain containing genetically attenuated endotoxin and a mutant sub-family B FHbp antigen with low FH binding, or with MenB-4C, which contains a recombinant sub-family B FHbp antigen that binds human FH, and three other antigens, NHba, NadA and PorA P1.4, capable of eliciting bactericidal antibody. The NOMV-FHbp elicited serum bactericidal activity against 12 of 13 serogroup A, B, W or X strains from Africa, and four isogenic serogroup B mutants with sub-family B FHbp sequence variants. There was no activity against a serogroup B mutant with sub-family A FHbp, or two serogroup C isolates from a recent outbreak in Northern Nigeria, which were mismatched for both PorA and sub-family of the FHbp vaccine antigen. For MenB-4C, NHba was expressed by all 16 African isolates tested, FHbp sub-family B in 13, and NadA in five. However, MenB-4C elicited titers ≥ 1:10 against only one isolate, and against only two of four serogroup B mutant strains with sub-family B FHbp sequence variants. NOMV-FHbp has greater potential to confer serogroup-independent protection in Africa than the licensed MenB-4C vaccine. However, the NOMV-FHbp vaccine will require inclusion of sub-family A FHbp for coverage against recent serogroup C strains causing outbreaks in Northern Nigeria. Copyright © 2015 Elsevier Ltd. All rights

  4. 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.

  5. Should remaining stockpiles of smallpox virus (variola) be destroyed?

    Science.gov (United States)

    Weinstein, Raymond S

    2011-04-01

    In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these cultures was first proposed. Recent studies suggest that variola and its experimental surrogate, vaccinia, have a remarkable ability to modify the human immune response through complex mechanisms that scientists are only just beginning to unravel. Further study that might require intact virus is essential. Moreover, modern science now has the capability to recreate smallpox or a smallpox-like organism in the laboratory in addition to the risk of nature re-creating it as it did once before. These factors strongly suggest that relegating smallpox to the autoclave of extinction would be ill advised.

  6. 77 FR 68783 - Prospective Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

    Science.gov (United States)

    2012-11-16

    ... Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for Disease..., filed 12/21/2007, entitled ``Development of Rift Valley Fever Virus Utilizing Reverse Genetics,'' US... (RVF) Viruses and Method of Use,'' PCT Application PCT/US2008/ 087023, filed 12/16/2008, entitled...

  7. [A short history of infectious diseases since the fifties of the last century and the importance of vaccination].

    Science.gov (United States)

    Marešová, Vilma

    2015-01-01

    Vaccination in the Czech lands has a long history; it begun during the Austro-Hungarian Empire in 1803 by vaccination against smallpox, and in the late 19th century by vaccination against rabies. In the second half of the 20th century, the basic vaccination included also other vaccines. Thanks to paediatricians, vaccination coverage of children was so high that in addition to the immunity of individuals the collective immunity was also significant. The incidence of infectious diseases has dropped significantly. Today the population, both medical and lay, almost does not know the classic childrens infectious diseases or their risk of complications. This creates a feeling in recent years that vaccination is unnecessary and that it is a source of complication and, therefore, better not to vaccinate. However, diseases, except for smallpox, have not disappeared, and for the susceptible unvaccinated individuals they represent a great risk. There are now occurring at atypical age groups where their diagnosis is even not considered. Therefore, it is important to return to the course of disease as well as to the potentially serious complications in unvaccinated people.

  8. Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.

    Science.gov (United States)

    Haber, Penina; Moro, Pedro L; Ng, Carmen; Lewis, Paige W; Hibbs, Beth; Schillie, Sarah F; Nelson, Noele P; Li, Rongxia; Stewart, Brock; Cano, Maria V

    2018-01-25

    Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons 18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations. Published by Elsevier Ltd.

  9. Sobre a varíola e as práticas da vacinação em Minas Gerais (Brasil no século XIX About smallpox and vaccination practices in Minas Gerais (Brazil in the 19th century

    Directory of Open Access Journals (Sweden)

    Anny Jackeline Torres Silveira

    2011-02-01

    Full Text Available Este artigo analisa o impacto da varíola e da prática da vacinação antivariólica em Minas Gerais durante o período imperial brasileiro (1822-1889. Apesar da presença de órgãos que visavam à organização e à propagação da vacina no país desde o início do século XIX, identifica-se, pela documentação relativa à saúde pública produzida pelas autoridades provinciais, uma série de fatores de natureza administrativa e cultural que influenciaram negativamente na plena implementação quer da vacina quer da estrutura organizada no período visando à sua difusão. Seguindo as proposições da historiografia dedicada ao tema, discute-se que, apesar da tendência à centralização observada em diferentes esferas da administração no processo de estruturação do Estado Imperial, no âmbito da saúde e, particularmente, no âmbito do serviço de vacinação antivariólica, prevaleceu uma desarticulação entre os diferentes agentes responsáveis pela implementação e o controle desse serviço. Outro aspecto que contribuiu para as dificuldades relativas à implementação desse serviço foi a grande resistência da população em submeter-se à vacina e que pode ser entendida pela análise das percepções sociais construídas sobre a doença e o método da vacinação.This article discusses the impact of smallpox and vaccination practices used against the disease used in the province of Minas Gerais, in Brazil, during the Imperial Period (1822-1889. Despite the existence of services responsible for the organization and dissemination of the vaccine in the country since the early 19th century, some administrative and cultural factors, as identified in documents produced by the province's public health authorities at the time, had a negative impact upon the full implementation of both practice and organization of services aimed at the dissemination of smallpox vaccination. Based upon historiographic sources, it is argued that despite

  10. Vaccines for the 21st century: a tool for decisionmaking

    National Research Council Canada - National Science Library

    Stratton, Kathleen R; Durch, Jane; Lawrence, Robert S

    Vaccines have made it possible to eradicate the scourge of smallpox, promise the same for polio, and have profoundly reduced the threat posed by other diseases such as whooping cough, measles, and meningitis. What is next...

  11. In Vitro Characterization of a Nineteenth-Century Therapy for Smallpox

    OpenAIRE

    Arndt, William; Mitnik, Chandra; Denzler, Karen L.; White, Stacy; Waters, Robert; Jacobs, Bertram L.; Rochon, Yvan; Olson, Victoria A.; Damon, Inger K.; Langland, Jeffrey O.

    2012-01-01

    In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarra...

  12. The history of vaccines and immunization: familiar patterns, new challenges.

    Science.gov (United States)

    Stern, Alexandra Minna; Markel, Howard

    2005-01-01

    Human beings have benefited from vaccines for more than two centuries. Yet the pathway to effective vaccines has been neither neat nor direct. This paper explores the history of vaccines and immunization, beginning with Edward Jenner's creation of the world's first vaccine for smallpox in the 1790s. We then demonstrate that many of the issues salient in Jenner's era-such as the need for secure funding mechanisms, streamlined manufacturing and safety concerns, and deep-seated public fears of inoculating agents-have frequently reappeared and have often dominated vaccine policies. We suggest that historical awareness can help inform viable long-term solutions to contemporary problems with vaccine research, production, and supply.

  13. The Florey lecture, 1983. Biological control, as exemplified by smallpox eradication and myxomatosis.

    Science.gov (United States)

    Fenner, F

    1983-06-22

    Biological control is an important method of dealing with plant and insect pests. The control of rabbits by myxomatosis and the eradication of smallpox by vaccination are unusual examples of biological control, in that they involve a vertebrate and a viral pest respectively. Myxomatosis is a benign disease in Sylvilagus rabbits in South America which is transmitted mechanically by mosquitoes. In the European rabbit, Oryctolagus, which is a pest in Australia and England, the virus from Sylvilagus produces a generalized disease that is almost always lethal. Myxomatosis was deliberately introduced into Australia in 1950 and into Europe in 1952. It was at first spectacularly successful in controlling the rabbit pest, but biological adjustments occurred in the virulence of the virus and the genetic resistances of rabbits. After 30 years of interaction, natural selection has resulted in a balance at a fairly high level of viral virulence. Smallpox has been a major scourge of mankind for over 1500 years. It spread from Asia to Europe in the Middle ages and from Europe to Africa and the Americas in the 15th and 16th centuries. Jenner's cowpox vaccine provided a method of control that reduced the severity of the disease during the 19th century but failed to eliminate the disease from many countries before the 1930s. Thereafter it was eradicated from Europe and North America, but remained endemic in South America, Africa and Asia. In 1967 it was still endemic in 33 countries and W.H.O. established a programme for global eradication within 10 years. The goal was achieved in 1977. Problems of the eradication programme and reasons for its success will be described.

  14. A New Document on Smallpox Vaccination.

    Science.gov (United States)

    Tayarani-Najaran, Zahra; Tayarani-Najaran, Nilufar; Sahebkar, Amirhossein; Emami, Seyed Ahmad

    2016-12-01

    Modern medicine owes much to the invaluable heritage of the practices of past generations and their achievements that have now become medical rules. In the case of vaccination, there is evidence that the nomads of Baluchistan (Southeast Iran) demonstrated natural immunization against cowpox, a practice that was later introduced to the medical community by Edward Jenner. Although the discoveries of scientists cannot be ignored, they are certainly based on the traditional and indigenous experiences that have been transferred from generation to generation until reaching us. Copyright © 2016. Published by Elsevier B.V.

  15. A New Document on Smallpox Vaccination

    Directory of Open Access Journals (Sweden)

    Zahra Tayarani-Najaran

    2016-12-01

    Full Text Available Modern medicine owes much to the invaluable heritage of the practices of past generations and their achievements that have now become medical rules. In the case of vaccination, there is evidence that the nomads of Baluchistan (Southeast Iran demonstrated natural immunization against cowpox, a practice that was later introduced to the medical community by Edward Jenner. Although the discoveries of scientists cannot be ignored, they are certainly based on the traditional and indigenous experiences that have been transferred from generation to generation until reaching us.

  16. L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines.

    Science.gov (United States)

    Pacchioni, Sole Maria; Bissa, Massimiliano; Zanotto, Carlo; Morghen, Carlo De Giuli; Illiano, Elena; Radaelli, Antonia

    2013-04-11

    The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most effective control and new vectors have been developed to generate recombinant vaccines against smallpox that induce the same immunogenicity as the traditional one. As protective antibodies are mainly directed against the surface proteins of the two infectious forms of vaccinia, the intracellular mature virions and the extracellular virions, combined proteins from these viral forms can be used to better elicit a complete and protective immunity. Four novel viral recombinants were constructed based on the fowlpox genetic background, which independently express the vaccinia virus L1 and A27 proteins present on the mature virions, and the A33 and B5 proteins present on the extracellular virions. The correct expression of the transgenes was determined by RT-PCR, Western blotting, and immunofluorescence. Using immunoprecipitation and Western blotting, the ability of the proteins expressed by the four novel FPL1R, FPA27L, FPA33R and FPB5R recombinants to be recognized by VV-specific hyperimmune mouse sera was demonstrated. By neutralisation assays, recombinant virus particles released by infected chick embryo fibroblasts were shown not be recognised by hyperimmune sera. This thus demonstrates that the L1R, A27L, A33R and B5R gene products are not inserted into the new viral progeny. Fowlpox virus replicates only in avian species, but it is permissive for entry and transgene expression in mammalian cells, while being immunologically non-cross-reactive with vaccinia virus. These recombinants might

  17. 77 FR 68783 - Prospective Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

    Science.gov (United States)

    2012-11-16

    ... Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for... Valley Fever Virus Utilizing Reverse Genetics,'' US Provisional Application 61/042,987, filed 4/7/2008, entitled ``Recombinant Rift Valley Fever (RVF) Viruses and Method of Use,'' PCT Application PCT/US2008...

  18. Diagnosing smallpox: would you know it if you saw it?

    Science.gov (United States)

    Woods, Ryan; McCarthy, Tara; Barry, M Anita; Mahon, Barbara

    2004-01-01

    The intentional release of anthrax in the United States in 2001 and other recent acts of terrorism have highlighted the possibility of intentional release of smallpox by terrorists. Little is known about physicians' ability to diagnose smallpox, especially in the critical first days, when the potential for rapid control of transmission is greatest. During December 2002 and January 2003, primary care and emergency physicians at a large urban academic medical center were surveyed regarding the diagnosis and management of patients who present with vesicular rash illness. In addition to demographic and training-related questions, the questionnaire included items about perceived comfort in diagnosing and evaluating rashes, knowledge of the key differential diagnostic characteristics of chickenpox and smallpox, and the diagnostic interpretation of color photographs of patients with smallpox or chickenpox. Responses were summarized as a perceived comfort score, a differential diagnosis score, and a picture score. Of 266 eligible physicians, 178 (67%) responded. Of these, 95% thought clinicians need more education about bioterrorism; only 17% reported comfort in diagnosing smallpox. Although most physicians recognized pictures of smallpox and chickenpox, only 36% correctly answered 3 of 4 questions regarding differential diagnosis, an important aspect of identifying cases early. Those who were comfortable diagnosing rash illnesses had higher differential diagnosis scores. Strategies for bioterrorism-related training could take advantage of physicians' awareness of their own knowledge deficits.

  19. Development of the small-molecule antiviral ST-246® as a smallpox therapeutic

    Science.gov (United States)

    Grosenbach, Douglas W; Jordan, Robert; Hruby, Dennis E

    2011-01-01

    Naturally occurring smallpox has been eradicated, yet it remains as one of the highest priority pathogens due to its potential as a biological weapon. The majority of the US population would be vulnerable in a smallpox outbreak. SIGA Technologies, Inc. has responded to the call of the US government to develop and supply to the Strategic National Stockpile a smallpox antiviral to be deployed in the event of a smallpox outbreak. ST-246® (tecovirimat) was initially identified via a high-throughput screen in 2002, and in the ensuing years, our drug-development activities have spanned in vitro analysis, preclinical safety, pharmacokinetics and efficacy testing (all according to the ‘animal rule’). Additionally, SIGA has conducted Phase I and II clinical trials to evaluate the safety, tolerability and pharmacokinetics of ST-246, bringing us to our current late stage of clinical development. This article reviews the need for a smallpox therapeutic and our experience in developing ST-246, and provides perspective on the role of a smallpox antiviral during a smallpox public health emergency. PMID:21837250

  20. Smallpox as a Bioweapon: Should We Be Concerned?

    Science.gov (United States)

    2012-03-01

    73  A.  DOES THIS TYPE OF ATTACK MATCH A PARTICULAR IDEOLOGY ...apply to smallpox. Smallpox is a virus of the Orthopox genus and the Poxviridae family, also known by the scientific name of Variola. It is easy to...they claim to possess, but it is evident that nothing in their stated ideology indicates they would abstain from using those that they could attain

  1. Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

    Science.gov (United States)

    Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

    2009-12-01

    Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

  2. Public fear of vaccination: separating fact from fiction.

    Science.gov (United States)

    Amanna, Ian; Slifka, Mark K

    2005-01-01

    During the last two centuries, the world has seen a substantial increase in the number and availability of vaccines for the prevention of infectious disease. Smallpox vaccine remains the most celebrated vaccine-related achievement in human history, but worldwide reductions in many other diseases including measles, mumps, rubella, polio, diphtheria, and whooping cough (Bordetella pertussis) also illustrate the power of vaccination in controlling outbreaks of contagious diseases. Ironically, as advances in vaccination successfully limit disease outbreaks, the impact that these infectious agents once had on society becomes marginalized. Public confidence in vaccination may erode because of real or perceived risks associated with immunization, and this in turn may lead to lower vaccination coverage and loss of herd immunity. Here, we will discuss some of the elements associated with public perceptions and fear of vaccination and place these into the context of how deadly several vaccine-preventable childhood diseases can be if vaccination coverage is insufficient.

  3. Vaccines for the 21st century

    Science.gov (United States)

    Delany, Isabel; Rappuoli, Rino; De Gregorio, Ennio

    2014-01-01

    In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. PMID:24803000

  4. O sentido da vacina ou quando o prever é um dever The meaning of vaccine or when predicting is a duty

    Directory of Open Access Journals (Sweden)

    Myriam Bahia Lopes

    1996-06-01

    Full Text Available Partindo da historiografia, analisamos a construção do monumento da medicina científica: a vacina antivariólica. Ao criar e difundir a vacina, a medicina demonstra como a técnica controla a vicia em escala planetária. A grande vitória da medicina científica se funda no seguinte resultado: hoje, a existência do vírus cia varíola depende da vida em laboratório. O movimento antivacinista surge na década de 1870, na Inglaterra, e questiona a adoção universal e obrigatória da vacina antivariólica. Estudamos algumas metáforas e analogias empregadas por médicos e historiadores. Elas nos revelam o processo de construção do fato vacina.From the perspective of historiography, the article analyzes the construction of scientific medicine's major landmark: the small-pox vaccine. When this vaccine was created and widely distributed, the medical field demonstrated how technology controls life on a planetary scale. The great victory of scientific medicine rests on the fact that today the life of the small-pox virus depends upon laboratory conditions. Born in England during the 1870's, the anti-vaccine movement questioned universal, mandatory small-pox vaccination. The article examines some metaphors and analogies used by physicians and historians, revealing the process by which the vaccine, as a phenomenon, was constructed.

  5. In vitro characterization of a nineteenth-century therapy for smallpox.

    Directory of Open Access Journals (Sweden)

    William Arndt

    Full Text Available In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections.

  6. In vitro characterization of a nineteenth-century therapy for smallpox.

    Science.gov (United States)

    Arndt, William; Mitnik, Chandra; Denzler, Karen L; White, Stacy; Waters, Robert; Jacobs, Bertram L; Rochon, Yvan; Olson, Victoria A; Damon, Inger K; Langland, Jeffrey O

    2012-01-01

    In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections.

  7. Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution

    Directory of Open Access Journals (Sweden)

    Emma Rey-Jurado

    2018-01-01

    Full Text Available Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.

  8. Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution.

    Science.gov (United States)

    Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K; Carreño, Leandro J; Riedel, Claudia A; Bueno, Susan M; Genzel, Yvonne; Kalergis, Alexis M

    2018-01-01

    Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.

  9. The eradication of smallpox--an overview of the past, present, and future.

    Science.gov (United States)

    Henderson, Donald A

    2011-12-30

    The 30th anniversary of the declaration of smallpox eradication is a propitious time to look back on the evolutionary history of the program, its execution, and its legacy for the future. The eradication of history's most feared disease culminated a decade-long World Health Organization campaign which began despite skepticism and doubt and succeeded despite a never ending array of obstacles occasioned by floods, civil war, famine, and bureaucratic inertia. New concepts in public health management, surveillance, and the application of large-scale programs for vaccination were fostered and matured. A new generation of young health workers emerged who applied new approaches and experienced the gratification of public health achievement. A definitive legacy for the future was the extension of the program into an "Expanded Program on Immunization", now functioning world-wide and resulting in dramatic improvements in health through control of vaccine-preventable diseases. No less important are the growing number of multi-national programs whose foundations rest on the development of active case surveillance to measure achievement and to guide progress - poliomyelitis, measles, guinea worm, and rubella. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. The Migration of Smallpox and Its Indelible Footprint on Latin American History. Junior Division Winner.

    Science.gov (United States)

    Thomson, Mark

    1998-01-01

    Addresses the migration of smallpox into the New World where it caused the extinction of entire indigenous civilizations and altered the survivors' cultures. Discusses the historical origins of smallpox and highlights the migration and consequences of smallpox in Central and South America. Includes an annotated bibliography, research description,…

  11. Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa

    Science.gov (United States)

    Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa

    2017-01-01

    ABSTRACT Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12–15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1–3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued. PMID:28340322

  12. Variola minor in coalfield areas of England and Wales, 1921-34: Geographical determinants of a national smallpox epidemic that spread out of effective control.

    Science.gov (United States)

    Smallman-Raynor, Matthew R; Rafferty, Sarah; Cliff, Andrew D

    2017-05-01

    This paper uses techniques of binary logistic regression to identify the spatial determinants of the last national epidemic of smallpox to spread in England and Wales, the variola minor epidemic of 1921-34. Adjusting for age and county-level variations in vaccination coverage in infancy, the analysis identifies a dose-response gradient with increasing odds of elevated smallpox rates in local government areas with (i) medium (odds ratio [OR] = 5.32, 95% Confidence Interval [95% CI] 1.96-14.41) and high (OR = 11.32, 95% CI 4.20-31.59) coal mining occupation rates and (ii) medium (OR = 16.74, 95% CI 2.24-125.21) and high (OR = 63.43, 95% CI 7.82-497.21) levels of residential density. The results imply that the spatial transmission of variola virus was facilitated by the close spatial packing of individuals, with a heightened transmission risk in coal mining areas of the country. A syndemic interaction between common respiratory conditions arising from exposure to coal dust and smallpox virus transmission is postulated to have contributed to the findings. We suggest that further studies of the geographical intersection of coal mining and acute infections that are transmitted via respiratory secretions are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. How long ago did smallpox virus emerge?

    Science.gov (United States)

    Shchelkunov, Sergei N

    2009-01-01

    Unlike vertebrates, for which paleontological data are available, and RNA viruses, which display a high rate of genetic variation, an objective estimate of time parameters for the molecular evolution of DNA viruses, which display a low rate of accumulation of mutations, is a complex problem. Genomic studies of a set of smallpox (variola) virus (VARV) isolates demonstrated the patterns of phylogenetic relationships between geographic variants of this virus. Using archival data on smallpox outbreaks and the results of phylogenetic analyses of poxvirus genomes, different research teams have obtained contradictory data on the possible time point of VARV origin. I discuss the approaches used for dating of VARV evolution and adduce the arguments favoring its historically recent origin.

  14. [EVALUATION OF THE HUMAN SENSITIVITY TO SMALLPOX VIRUS BY THE PRIMARY CULTURES OF THE MONOCYTE-MACROPHAGES].

    Science.gov (United States)

    Zamedyanskaya, A S; Titova, K A; Sergeev, Al A; Kabanov, A S; Bulychev, L E; Sergeev, Ar A; Galakhova, D O; Nesterov, A E; Nosareva, O V; Shishkina, L N; Taranov, O S; Omigov, V V; Agafonov, A P; Sergeev, A N

    2016-01-01

    Studies of the primary cultures of granulocytes, mononuclear, and monocyte-macrophage cells derived from human blood were performed using variola virus (VARV) in the doses of 0.001-0.021 PFU/cell (plaques-forming units per cell). Positive dynamics of the virus accumulation was observed only in the monocyte-macrophages with maximum values of virus concentration (5.0-5.5 Ig PFU/ml) mainly within six days after the infection. The fact of VARV replication in the monocyte-macrophages was confirmed by the data of electron microscopy. At the same time, virus vaccines when tested in doses 3.3 and 4.2 Ig PFU/ml did not show the ability to reproduce in these human cells. The people sensitivity to VARV as assessed from the data obtained on human monocyte-macrophages corresponded to -1 PFU (taking into account the smooth interaction of the virus in the body to the cells of this type), which is consistent to previously found theoretical data on the virus sensitivity. The human susceptibility to VARV assessed experimentally can be used to predict the adequacy of developed smallpox models (in vivo) based on susceptible animals. This is necessary for reliable assessment of the efficiency of development of drugs for treatment and prophylaxis of the smallpox.

  15. Live attenuated vaccines: Historical successes and current challenges.

    Science.gov (United States)

    Minor, Philip D

    2015-05-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. 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

  18. 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.

  19. 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 ...

  20. 42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

    Science.gov (United States)

    2010-10-01

    ... inflammatory cells in the dermis of the skin at the vaccination or inoculation site. The diagnosis of PV may be... the mother that results from the placental transmission of the vaccinia virus during any time in the... membrane lesion containing an accumulation of white blood cells. (8) Recipient means a person to whom the...

  1. Distinction between infections with European and American/vaccine type PRRS virus after vaccination with a modified-live PRRS virus vaccine

    DEFF Research Database (Denmark)

    Bøtner, Anette; Strandbygaard, Bertel; Sørensen, K. J.

    2000-01-01

    In July 1996 a modified live Porcine reproductive and respiratory syndrome (PRRS) vaccine, based on an American (US) strain of the PRRS virus (PRRSV), was licensed in Denmark. The vaccine was licensed for use in 3-18 week old pigs, exclusively. Starting during the middle of October 1996, several...... herds who had recently begun vaccination, experienced acute PRRS-like symptoms including an increasing number of abortions and stillborn piglets and an increasing mortality in the nursing period. During the period from October 1996 until May 1997, the PRRS virus (PRRSV), identified as the vaccine....../US type of PRRSV, was isolated from fetuses, dead piglets, pleural fluids and/or lung tissues from 114 of such herds. These findings indicated the spread of the vaccine virus to non-vaccinated sows followed by transplacental infection of fetuses. Also, a number of not previously PRRSV infected and non...

  2. Political epidemiology: strengthening socio-political analysis for mass immunisation - lessons from the smallpox and polio programmes.

    Science.gov (United States)

    Taylor, S

    2009-01-01

    Control and reduction of infectious diseases is a key to attaining the Millennium Development Goals. An important element of this work is the successful immunisation, especially in resource-poor countries. Mass immunisation, most intensively in the case of eradication, depends on a combination of reliable demand (e.g. public willingness to comply with the vaccine protocol) and effective supply (e.g. robust, generally state-led, vaccine delivery). This balance of compliance and enforceability is, quintessentially, socio-political in nature - conditioned by popular perceptions of disease and risk, wider conditions of economic development and poverty, technical aspects of vaccine delivery, and the prevailing international norms regarding power relations between states and peoples. In the past 100 years, three out of six disease eradication programmes have failed. The explanations for failure have focused on biotechnical and managerial or financial issues. Less attention is paid to socio-political aspects. Yet socio-political explanations are key. Eradication is neither inherently prone to failure, nor necessarily doomed in the case of polio. However, eradication, and similar mass immunisation initiatives, which fail to address social and political realities of intervention may be. A comparison of the smallpox and polio eradication programmes illustrates the importance of disease-specific socio-political analysis in programme conceptualisation, design, and management.

  3. Smallpox: What the dermatologist should know

    NARCIS (Netherlands)

    Spuls, Phyllis I.; Bos, Jan D.; Rudikoff, Donald

    2004-01-01

    Despite the eradication of naturally occurring smallpox in 1977, stores of the virus have been maintained in laboratories in the United States and Russia. It is feared that certain rogue states and terrorist organizations may have illicitly acquired the virus with the intent of unleashing it as an

  4. Vaccines for prevention of group B meningococcal disease: Not your father's vaccines.

    Science.gov (United States)

    Harrison, Lee H

    2015-11-27

    For decades, there was no licensed vaccine for prevention of endemic capsular group B meningococcal disease, despite the availability of vaccines for prevention of the other most common meningococcal capsular groups. Recently, however, two new vaccines have been licensed for prevention of group B disease. Although immunogenic and considered to have an acceptable safety profile, there are many scientific unknowns about these vaccines, including effectiveness against antigenically diverse endemic meningococcal strains; duration of protection; whether they provide any herd protection; and whether there will be meningococcal antigenic changes that will diminish effectiveness over time. In addition, these vaccines present societal dilemmas that could influence how they are used in the U.S., including high vaccine cost in the face of a historically low incidence of meningococcal disease. These issues are discussed in this review. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

  5. [Role of vaccination in animal health].

    Science.gov (United States)

    Pastoret, Paul-Pierre

    2012-03-01

    According to the IFAH, veterinary vaccines currently account for 26% of the global market in veterinary medicines, reflecting the importance of vaccines in animal health, as well as the number of wild and domesticated target species, and the monospecific nature of most vaccines. Multispecies vaccines include tetanus and rabies. In 2010, the number of food-producing animals was estimated to be roughly 20 billion and is rising gradually. Fowl currently represent the main food species. Veterinary vaccination has allowed the eradication of rinderpest, as officially declared last year (2011), jointly by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation of the United Nations (FAO). Rinderpest was a real scourge, and was only the second viral disease to be totally eradicated (after human smallpox). One characteristic of veterinary vaccination is the DIVA approach, "differentiating infected from vaccinated animals". The DIVA strategy is especially interesting for regulated control of diseases like foot-and-mouth disease, infectious bovine rhinotracheitis, pseudorabies, and classical swine fever. DIVA vaccination requires prior serological testing. Vaccination is also used for wild animals such as foxes (rabies) and wild boars (classical swine fever). "In ovo" vaccination of fowl on day 18 of the incubation period is used to prevent Marek's disease for instance, and double vaccination (vector and insert) to prevent both Marek's disease and Gumboro's disease in fowl. Animal vaccination can also help to protect human health, as illustrated by fowl vaccination against salmonellosis.

  6. Translational mini-review series on vaccines: The Edward Jenner Museum and the history of vaccination.

    Science.gov (United States)

    Morgan, A J; Parker, S

    2007-03-01

    Edward Jenner's discovery of vaccination must rank as one of the most important medical advances of all time and is a prominent example of the power of rational enquiry being brought to bear during the Age of Enlightenment in 18th century Europe. In the modern era many millions of lives are saved each year by vaccines that work essentially on the same principles that were established by Edward Jenner more than 200 years ago. His country home in Berkeley, Gloucestershire, is where he carried out his work and where he spent most of his life. The building is now a museum in which the life and times of Jenner are commemorated including not only the discovery of smallpox vaccination but also his other important scientific contributions to natural history and medicine. The trustees of the Edward Jenner museum are committed to promoting the museum as a real and "virtual" educational centre that is both entertaining and informative.

  7. 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.

  8. Varíola e vacina no Brasil no século XX: institucionalização da educação sanitária Smallpox and vaccine in Brazil at 20th century: institutionalization of health education

    Directory of Open Access Journals (Sweden)

    Tania Maria Dias Fernandes

    2011-02-01

    Full Text Available O objetivo deste texto é discutir algumas ações que possibilitaram a erradicação da varíola no Brasil, considerando os principais contextos e as políticas adotadas para as doenças entre 1920 e 1970, assumindo como destaque as medidas educativas no campo da saúde e estabelecendo uma discussão acerca do conteúdo educacional dos programas adotados. Observam-se, ao longo deste período, a configuração de políticas de saúde e a criação de organismos estatais direcionados a doenças e ações específicas, o que no caso da varíola somente ocorreu na década de 1960, quando foram criadas a Campanha Nacional contra a Varíola e a Campanha Nacional de Erradicação da Varíola. A educação sanitária e as relações com estas instituições foram de fundamental importância para a divulgação e implementação de ações estatais que possibilitaram ampliação da cobertura vacinal com a aceitação de seu uso pela população, o alcance do controle e a erradicação da doença.The aim of this paper is to discuss some actions that made possible the eradication of smallpox in Brazil, considering the main contexts and policies adopted for the disease between 1920 and 1970, assuming as contrast educational measures in the field of health and establishing a discussion on the educational content of the programs adopted. It can be observed that, during this period, the setting of the health policies and the creation of state agencies that target specific diseases and actions, which in the case of the smallpox, only occurred in the 1960s, when the National Campaign against the Smallpox and the National Campaign for Eradication of Smallpox were created. Health education and the relations with these institutions were of fundamental importance to the dissemination and implementation of state actions that allowed the expansion of the vaccinal coverage with acceptance of its use by the population and the range of control and eradication of the

  9. Lessons for Implementation from the World's Most Successful Programme: The Global Eradication of Smallpox.

    Science.gov (United States)

    Pratt, David

    1999-01-01

    Focuses on lessons educators might learn from the Intensified Campaign for the Global Eradication of Smallpox. Outlines the history of smallpox eradication. Discusses the eradication effort's obstacles, campaign, and costs and benefits. Considers five factors relevant to the successful implementation of educational programs. (CMK)

  10. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

    2006-04-11

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

  11. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

    2006-01-01

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

  12. Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

    Science.gov (United States)

    Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

    2017-10-09

    Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

  13. Challenges and solutions for a rational vaccine design for TB-endemic regions.

    Science.gov (United States)

    Gowthaman, Uthaman; Mushtaq, Khurram; Tan, Amabel C; Rai, Pradeep K; Jackson, David C; Agrewala, Javed N

    2015-01-01

    Vaccines have been successful for global eradication or control of dreaded diseases such as smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, this success has not been achieved for controlling tuberculosis (TB) worldwide. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered success in the Western world but has failed in TB-endemic areas. In this article, we highlight and discuss the aspects of immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. In addition, we also suggest strategies that contribute toward the development of successful vaccine in protecting populations where BCG has failed.

  14. New insights about host response to smallpox using microarray data

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    Dias Rodrigo A

    2007-08-01

    Full Text Available Abstract Background Smallpox is a lethal disease that was endemic in many parts of the world until eradicated by massive immunization. Due to its lethality, there are serious concerns about its use as a bioweapon. Here we analyze publicly available microarray data to further understand survival of smallpox infected macaques, using systems biology approaches. Our goal is to improve the knowledge about the progression of this disease. Results We used KEGG pathways annotations to define groups of genes (or modules, and subsequently compared them to macaque survival times. This technique provided additional insights about the host response to this disease, such as increased expression of the cytokines and ECM receptors in the individuals with higher survival times. These results could indicate that these gene groups could influence an effective response from the host to smallpox. Conclusion Macaques with higher survival times clearly express some specific pathways previously unidentified using regular gene-by-gene approaches. Our work also shows how third party analysis of public datasets can be important to support new hypotheses to relevant biological problems.

  15. The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of smallpox disease.

    Science.gov (United States)

    Trost, Lawrence C; Rose, Michelle L; Khouri, Jody; Keilholz, Laurie; Long, James; Godin, Stephen J; Foster, Scott A

    2015-05-01

    Brincidofovir (BCV) has broad-spectrum in vitro activity against dsDNA viruses, including smallpox, and is being developed as a treatment for smallpox as well as infections caused by other dsDNA viruses. BCV has previously been shown to be active in multiple animal models of smallpox. Here we present the results of a randomized, blinded, placebo-controlled study of the efficacy and pharmacokinetics of a novel, "humanized" regimen of BCV for treatment of New Zealand White rabbits infected with a highly lethal inoculum of rabbitpox virus, a well characterized model of smallpox. Compared with placebo, a dose-dependent increase in survival was observed in all BCV-treatment groups. Concentrations of cidofovir diphosphate (CDV-PP), the active antiviral, in rabbit peripheral blood mononuclear cells (PBMCs) were determined for comparison to those produced in humans at the dose proposed for treatment of smallpox. CDV-PP exposure in PBMCs from rabbits given BCV scaled to human exposures at the dose proposed for treatment of smallpox, which is also currently under evaluation for other indications. The results of this study demonstrate the activity of BCV in the rabbitpox model of smallpox and the feasibility of scaling doses efficacious in the model to a proposed human dose and regimen for treatment of smallpox. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Resister's logic: the anti-vaccination arguments of Alfred Russel Wallace and their role in the debates over compulsory vaccination in England, 1870-1907.

    Science.gov (United States)

    Fichman, Martin; Keelan, Jennifer E

    2007-09-01

    In the 1880s, Alfred Russel Wallace, the celebrated co-discoverer of natural selection, launched himself into the centre of a politicised and polarised debate over the unpopular compulsory vaccination laws in England. Wallace never wavered in his belief that smallpox vaccination was useless and likely dangerous. Six years before his death, the anti-vaccinationists successfully secured a conscience clause that effectively dismantled the compulsory vaccination laws. Several other important Victorian scientists joined Wallace in the fight to repeal compulsory vaccination arguing that widely held views on the effectiveness of vaccination and evidence for immunity were inconclusive in the light of (then) contemporary standards of evidence. This article situates Wallace's anti-vaccination logic within the broader matrix of sociopolitical and cultural reform movements of the late Victorian era. Additionally it provides the first detailed analysis of his critique of vaccination science, in particular the role statistics played in his arguments. In this period, both pro-vaccinationists and anti-vaccinationists invested great efforts in collating and analysing statistical data sets that either supported or refuted the claims of vaccination's effectiveness. While each side presented 'controlled' case studies to support their assertions, without an unambiguous test to measure or demonstrate vaccination's effectiveness, the anti-vaccinationists continued to mount credible statistical critiques of vaccination science.

  17. Vaccines in historic evolution and perspective: a narrative of vaccine discoveries.

    Science.gov (United States)

    Hilleman, M R

    2000-01-01

    The sciences of vaccinology and immunology were created only two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th- and early 20th-century biomedical sciences. The period from 1930 to 1950 was a transitional era, with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines. Modern vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given at a Meeting of the Institute of Human Virology entitled A Symposium on HIV-AIDS and Cancer Biology, Baltimore, Maryland, on August 30, 1999 and recounts, by invitation, more than 55 years of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references 1 and 2. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.

  18. Virus-Vectored Influenza Virus Vaccines

    Science.gov (United States)

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

    Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

  19. Ebola hemorrhagic Fever and the current state of vaccine development.

    Science.gov (United States)

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

    2014-12-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.

  20. [The world is free of pox - Implementation and success of a grandiose program].

    Science.gov (United States)

    Dittmann, S

    1980-12-15

    At the beginning of this century the compulsory vaccination and revaccination which was legally founded after the introduction of the vaccination by Jenner (1796) led to the removal of the smallpox in Europe and Northern America. However, up to the sixties in the developing countries of Asia, Africa as well as of Southern America and Middle America still fell ill and died of small-pox millions of people. Between 1953 and 1973 importations into countries of Europe and Northern America took place in 51 cases. In 1959 on the motion of the USSR the WHO decided performance of a world-wide eradication programme of small-pox which could be led to success with comprehensive personal, material and financial support of many countries. Flanking scientific, technological and methodical measures were of essential importance. In May 1980 the World Health Assembly in Geneva announced in solemn form the world-wide eradication of the small-pox and gave recommendations to the member countries for concluding measures concerning the small-pox vaccination, the foundation of vaccine reserves and the control of the epidemiological situation in the world. Also in the GDR the small-pox vaccination in childhood could be abolished.

  1. Serological studies on an outbreak of smallpox in the State of Bahia - Brazil in 1969

    Directory of Open Access Journals (Sweden)

    Eduardo de Azeredo Costa

    1972-01-01

    Full Text Available Four weeks after Containment Vaccination undertaken against the largest outbreak of smallpox occured in Brazil in 1969, that of the municipality of Utinga, Bahia, 99 samples of serum were collected from the local population. These samples were classified in four groups: a - Individuals with a history of variola prior to the beginning of present outbreak in town (15 sera; "Previous smallpox group"; b - Individuals with primary vaccination, with no record variola, at the time of containment measures (15 sera. "Primary vaccinated group"; c - Individuals with no previous record of variola revaccinated with "take" at the time of containment (15 sera0, "Revaccinated group"; d - Individuals who contracted variola in present outbreak (54 sera these were subdivided in four sub-groups, according to dates on which cases ocurred, "Variola in outbreak group". Serological study of samples was done by tests of hemagglutination inhibition, neutralization, and complement fixation. It was observed that HI titers were significantly lower in cases of previous smallpox than in other groups. Although they were slightly higher on revaccinated individuals than on primary vaccinated group and than in the group of variola in outbreak, this difference was not significant. Those same antibodies were present in all cases of variola in outbreak, and it was found that titers decreased in direct proportion to time elapsed from occurrence of cases. Neutralizing antibodies proved to be significantly higher on the revaccinated group than on variola in outbreak group, and higher on these than on primary vaccinated and on the previous smallpox groups. In cases from the variola in outbreak it was verified that neutralizing antibodies remained stable, although with great variation in titers. Tests of complement fixation could not be undertaken on all samples, because many of them proved to have anticomplementarity. However, it was found that complement fixing antibodies diminished

  2. Are licensed canine parvovirus (CPV2 and CPV2b) vaccines able to elicit protection against CPV2c subtype in puppies?: A systematic review of controlled clinical trials.

    Science.gov (United States)

    Hernández-Blanco, Beatriz; Catala-López, Ferrán

    2015-10-22

    Severe gastroenteritis caused by canine parvovirus type 2 (CPV2) is a serious life-threatening disease in puppies less than 4-months of age. The emergence of new variants has provoked some concern about the cross-protection elicited by licensed canine parvovirus modified-live type 2 (CPV2) and type 2b (CPV2b) vaccines against the most recent subtype CPV2c. A systematic review was carried out to assess the efficacy of commercial vaccines. We conducted a literature search of Pub Med/MEDLINE from January 1990 to May 2014. This was supplemented by hand-searching of related citations and searches in Google/Google Scholar. Controlled clinical trials in which vaccinated puppies were challenged with CPV2c virus were evaluated. Reporting of outcome measures and results for vaccine efficacy were critically appraised through a variety of clinical signs, serological tests, virus shedding and the ability to overcome maternally derived antibodies (MDA) titres. Six controlled clinical trials were included in the review. In most cases, the results of the selected studies reported benefits in terms of clinical signs, serological tests and virus shedding. However, MDA interference was not considered or evaluated in 5 of the selected trials. No accurate definitions of baseline healthy status and/or clinical outcomes were provided. Methods of randomization, allocation concealment and blinding were usually poorly reported. As a result of the limited number of included studies matching the inclusion criteria, the small sample sizes, short follow-up and the methodological limitations observed, it was not possible to reach a final conclusion regarding the cross-protection of licensed CPV2 and CPV2b vaccines against the subtype 2c in puppies. Further and specifically designed trials are required in order to elucidate whether cross-protection is acquired from licensed CPV vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Infection prevention and mass vaccination training for U.S. point of dispensing staff and volunteers: a national study.

    Science.gov (United States)

    Rebmann, Terri; Loux, Travis M; Zink, Thomas K; Swick, Zachary; Wakefield, Mary

    2015-03-01

    Points of dispensing (PODs) are deployed for medical countermeasure mass dispensing. However, infection prevention and vaccine administration pre-event training offered and just-in-time (JIT) education planned for POD workers have not been assessed. Disaster planners were sent an online questionnaire in 2013. McNemar tests compared training offered to staff versus volunteers and pre-event training versus JIT training. In total, 301 disaster planners participated. The most frequent pre-event training included hand hygiene (59.1% and 28.0%) and personal protective equipment (PPE) selection (52.1% and 24.1%) for staff and volunteers, respectively. Few provided pre-event training on the cold chain technique (14.8% and 5.1%) or smallpox vaccine administration (4.7% and 2.3%) for staff or volunteers. For all topics except smallpox vaccine administration, more staff than volunteers received pre-event training (P training includes hand hygiene (79.8% and 73.5%) and PPE selection (79.4% and 70.0%) to staff and volunteers. For all topics, more JIT education is planned for staff than volunteers (P training is planned than has been given pre-event for all topics (P training is needed on infection prevention and vaccine administration to ensure safe and successful POD deployment. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  4. Cationic lipid-formulated DNA vaccine against hepatitis B virus: immunogenicity of MIDGE-Th1 vectors encoding small and large surface antigen in comparison to a licensed protein vaccine.

    Directory of Open Access Journals (Sweden)

    Anne Endmann

    Full Text Available Currently marketed vaccines against hepatitis B virus (HBV based on the small (S hepatitis B surface antigen (HBsAg fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.

  5. 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. ...

  6. The US Military Commitment to Vaccine Development: A Century of Successes and Challenges

    Directory of Open Access Journals (Sweden)

    Silvia Ratto-Kim

    2018-06-01

    Full Text Available The US military has been a leading proponent of vaccine development since its founding. General George Washington ordered the entire American army to be variolated against smallpox after recognizing the serious threat that it posed to military operations. He did this on the recommendation from Dr. John Morgan, the physician-in-chief of the American army, who wrote a treatise on variolation in 1776. Although cases of smallpox still occurred, they were far fewer than expected, and it is believed that the vaccination program contributed to victory in the War of Independence. Effective military force requires personnel who are healthy and combat ready for worldwide deployment. Given the geography of US military operations, military personnel should also be protected against diseases that are endemic in potential areas of conflict. For this reason, and unknown to many, the US military has strongly supported vaccine research and development. Four categories of communicable infectious diseases threaten military personnel: (1 diseases that spread easily in densely populated areas (respiratory and dysenteric diseases; (2 vector-borne diseases (disease carried by mosquitoes and other insects; (3 sexually transmitted diseases (hepatitis, HIV, and gonorrhea; and (4 diseases associated with biological warfare. For each category, the US military has supported research that has provided the basis for many of the vaccines available today. Although preventive measures and the development of drugs have provided some relief from the burden of malaria, dengue, and HIV, the US military continues to fund research and development of prophylactic vaccines that will contribute to force health protection and global health. In the past few years, newly recognized infections with Zika, severe acute respiratory syndrome, Middle East respiratory syndrome viruses have pushed the US military to fund research and fast track clinical trials to quickly and effectively develop

  7. Vaccine refusal - what we need to know.

    Science.gov (United States)

    Succi, Regina Célia de Menezes

    2018-04-12

    Opposition to vaccines is not a new event, and appeared soon after the introduction of the smallpox vaccine in the late 18th century. The purpose of this review is to educate healthcare professionals about vaccine hesitancy and refusal, its causes and consequences, and make suggestions to address this challenge. A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and ScieLo databases from 1980 to the present day, using the terms "vaccine refusal," "vaccine hesitancy," and "vaccine confidence." The publications considered as the most relevant by the author were critically selected. The beliefs and arguments of the anti-vaccine movements have remained unchanged in the past two centuries, but new social media has facilitated the dissemination of information against vaccines. Studies on the subject have intensified after 2010, but the author did not retrieve any published studies to quantify this behavior in Brazil. The nomenclature on the subject (vaccine hesitancy) was standardized by the World Health Organization in 2012. Discussions have been carried out on the possible causes of vaccine hesitancy and refusal, as well as on the behavior of families and health professionals. Proposals for interventions to decrease public doubts, clarify myths, and improve confidence in vaccines have been made. Guides for the health care professional to face the problem are emerging. The healthcare professional is a key element to transmit information, resolve doubts and increase confidence in vaccines. They must be prepared to face this new challenge. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  8. Mistrust in Medicine: The Rise and Fall of America's First Vaccine Institute.

    Science.gov (United States)

    Lanzarotta, Tess; Ramos, Marco A

    2018-06-01

    In 1813, the American government passed An Act to Encourage Vaccination, the first federal endorsement of a medical practice in American history. The law tasked a federal agent with maintaining a supply of the smallpox vaccine and distributing it nationwide. James Smith, a well-respected physician and proponent of vaccination, was appointed as vaccine agent. Smith was skeptical of claims that only well-trained physicians should be allowed to perform vaccination; he felt it was a simple procedure that should be available to all American citizens. In 1822, he made a tragic error that caused several deaths and left him vulnerable to criticism from political opponents and his medical peers. This ended Smith's professional career and led to the repeal of the act itself. In this article, we use the rise and fall of James Smith to provide a historical perspective on contemporary debates surrounding delayed vaccination schedules. We explain how physicians-in the 19th century and today-have worked to build public trust in vaccination in an American culture suspicious of medical expertise.

  9. E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox

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    Asisa Volz

    2018-01-01

    Full Text Available The highly attenuated Modified Vaccinia virus Ankara (MVA lacks most of the known vaccinia virus (VACV virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins.

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

    Science.gov (United States)

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

    2016-10-01

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

  11. 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.

  12. Characterization of Two Historic Smallpox Specimens from a Czech Museum.

    Science.gov (United States)

    Pajer, Petr; Dresler, Jiri; Kabíckova, Hana; Písa, Libor; Aganov, Pavel; Fucik, Karel; Elleder, Daniel; Hron, Tomas; Kuzelka, Vitezslav; Velemínsky, Petr; Klimentova, Jana; Fucikova, Alena; Pejchal, Jaroslav; Hrabakova, Rita; Benes, Vladimir; Rausch, Tobias; Dundr, Pavel; Pilin, Alexander; Cabala, Radomir; Hubalek, Martin; Stríbrny, Jan; Antwerpen, Markus H; Meyer, Hermann

    2017-07-27

    Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe.

  13. 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 ...

  14. 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.

  15. Impact of imitation processes on the effectiveness of ring vaccination.

    Science.gov (United States)

    Wells, Chad R; Tchuenche, Jean M; Meyers, Lauren Ancel; Galvani, Alison P; Bauch, Chris T

    2011-11-01

    Ring vaccination can be a highly effective control strategy for an emerging disease or in the final phase of disease eradication, as witnessed in the eradication of smallpox. However, the impact of behavioural dynamics on the effectiveness of ring vaccination has not been explored in mathematical models. Here, we analyze a series of stochastic models of voluntary ring vaccination. Contacts of an index case base vaccinating decisions on their own individual payoffs to vaccinate or not vaccinate, and they can also imitate the behaviour of other contacts of the index case. We find that including imitation changes the probability of containment through ring vaccination considerably. Imitation can cause a strong majority of contacts to choose vaccination in some cases, or to choose non-vaccination in other cases-even when the equivalent solution under perfectly rational (non-imitative) behaviour yields mixed choices. Moreover, imitation processes can result in very different outcomes in different stochastic realizations sampled from the same parameter distributions, by magnifying moderate tendencies toward one behaviour or the other: in some realizations, imitation causes a strong majority of contacts not to vaccinate, while in others, imitation promotes vaccination and reduces the number of secondary infections. Hence, the effectiveness of ring vaccination can depend significantly and unpredictably on imitation processes. Therefore, our results suggest that risk communication efforts should be initiated early in an outbreak when ring vaccination is to be applied, especially among subpopulations that are heavily influenced by peer opinions.

  16. 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.

  17. Differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice

    NARCIS (Netherlands)

    Kaufman, David R.; Goudsmit, Jaap; Holterman, Lennart; Ewald, Bonnie A.; Denholtz, Matthew; Devoy, Colleen; Giri, Ayush; Grandpre, Lauren E.; Heraud, Jean-Michel; Franchini, Genoveffa; Seaman, Michael S.; Havenga, Menzo J. E.; Barouch, Dan H.

    2008-01-01

    The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding

  18. 42 CFR 102.50 - Medical records necessary to establish that a covered injury was sustained.

    Science.gov (United States)

    2010-10-01

    ... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed... to establish that a smallpox vaccine recipient or vaccinia contact sustained a covered injury, a... records, including the admission history and physical examination, the discharge summary, all physician...

  19. Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II

    Directory of Open Access Journals (Sweden)

    Boer Rob

    2006-05-01

    Full Text Available Abstract Background Because smallpox (variola major may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. Methods A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. Results 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R was 2 (range 0–38. The majority outbreaks were small (less than 5 cases and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1 and were prolonged if not initially recognized (median of 3 generations; outbreaks with mostly hospitalized patients had higher initial R values (median 12 and were shorter (median of 3 generations. Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases and longer (median of 3 generations compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation. Conclusion Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.

  20. Transmission patterns of smallpox: Systematic review of natural outbreaks in Europe and North America since World War II

    NARCIS (Netherlands)

    V. Bhatnagar (Vibha); M.A. Stoto (Michael); S.C. Morton (Sally); R. Boer (Rob); S.A. Bozzette (Samuel)

    2006-01-01

    textabstractBackground: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. Methods: A systematic review was used to identify papers from the National Library

  1. Study of adverse events following immunisation with universal and newer vaccines in the Serampore IMA Child Clinic over a period of 7 years.

    Science.gov (United States)

    Das, Pradip Kumar

    2013-04-01

    Immunisation is an important part of childcare practice. It is one of the most beneficial and cost effective measures for the prevention of diseases. From the previous retrospective studies, it was evident that smallpox has been completely eradicated throughout now-a-days with the wholehearted and sincere efforts of healthcare providers by applying efficient and safe vaccine against smallpox, same is true also to polio which is now close to worldwide eradication and measles and rubella are no longer endemic in certain parts of the world. Not only has that with the introduction of safer and more efficient newer vaccines, the incidence of most other vaccine preventable disease of childhood also reduced considerably. The aim of the present study is to estimate the incidence and clinical presentation of adverse events following immunisation with universal and newer vaccines for a period of seven years using prospective active surveillance. Children under the age of 7 years were taken for universal and newer scheduled vaccinations given in the Serampore IMA Child Clinic under the supervision of the clinicians maintaining strictly the guidelines of Expanded Programme of Immunisation (Government of India). This study of adverse events following immunisation in the Serampore IMA Child Clinic confirms that the adverse events such as fever (0.37%), pain and swelling at the site of injection (0.32%0, urticarial rash (0.02%), anaphylactic shock (0.003%) are negligible. There were only two reports of anaphylaxis following preschool and infant schedule vaccines, including measles, mumps and rubella (MMR), Haemophilus influenzae type B vaccines and typhoid vaccines in approximately 52,000 infants received over a period of 7 years starting from 1st April, 2005 to 31st March, 2012 and there were no deaths or longterm effects reported during the post follow-up period in the Serampore IMA Child Clinic.

  2. [Small pox--infection, therapy and anaesthesiological management (part 1)].

    Science.gov (United States)

    Langefeld, T W; Engel, J; Menges, T; Hempelmann, G

    2003-07-01

    Smallpox is an acute contagious and sometimes fatal infectious disease. It is caused by the variola-virus. Smallpox is characterized by a typical disease form with a progressive distinctive skin rash, especially at face, arms and legs. Smallpox has a fatality rate of about 30 % and the therapy of infected patients is only symptomatically. As prevention the WHO initiated worldwide vaccination programs in the year 1967. The last naturally occurring case of smallpox in the world was in Somalia in 1977. Since then the only known cases of smallpox happened from an outbreak in Birmingham, England caused by a laboratory accident in the year of 1979. On May the 8 th 1980 the disease was declared as eliminated from the world by the WHO (WHO-Resolution 33.33). A natural occurrence of the variola-virus seems to be not given. Nevertheless the virus exists for research in two laboratories, the American Centers of Disease Control and Prevention in Atlanta, Georgia and in the Russian Research Center for Virology and Biotechnics in Kolzowo, Sibiria. Threatening infections with smallpox or other microorganisms, used as bioweapons, get a new dimension through global terrorism. The variola-virus represents an optimal candidate for bioweapons. It is easy to replicate, it is highly contagious and the transmission over aerosol or direct contact from man to man is easy to handle. After the disease was eliminated from the world, routine vaccination among general public was stopped. Therefore younger people don't possess any vaccination protection. Older formerly vaccinated people probably have only a non-sufficient protection. Because of the smallpox elimination a lot of physicians have no experience with this disease. An outbreak of this smallpox isn't only controlled by new vaccination. In our times we need adapted prevention-standards, pox-alarm plans and quarantine standards.

  3. Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology.

    Science.gov (United States)

    Rodrigues, Ana F; Soares, Hugo R; Guerreiro, Miguel R; Alves, Paula M; Coroadinha, Ana S

    2015-09-01

    Vaccination is one of the most effective interventions in global health. The worldwide vaccination programs significantly reduced the number of deaths caused by infectious agents. A successful example was the eradication of smallpox in 1979 after two centuries of vaccination campaigns. Since the first variolation administrations until today, the knowledge on immunology has increased substantially. This knowledge combined with the introduction of cell culture and DNA recombinant technologies revolutionized vaccine design. This review will focus on vaccines against human viral pathogens, recent developments on vaccine design and cell substrates used for their manufacture. While the production of attenuated and inactivated vaccines requires the use of the respective permissible cell substrates, the production of recombinant antigens, virus-like particles, vectored vaccines and chimeric vaccines requires the use - and often the development - of specific cell lines. Indeed, the development of novel modern viral vaccine designs combined with, the stringent safety requirements for manufacture, and the better understanding on animal cell metabolism and physiology are increasing the awareness on the importance of cell line development and engineering areas. A new era of modern vaccinology is arriving, offering an extensive toolbox to materialize novel and creative ideas in vaccine design and its manufacture. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

    Science.gov (United States)

    Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

    2015-01-01

    Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

  5. Disease: H00372 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00372 Smallpox; Variola Smallpox is a contagious disease caused by the variola vi...al varieties of smallpox: variola major with a case fatality rate of 30% and variola minor with milder severity. Smallpox... millions of people. Infectious disease ... Variola virus [GN:T40082] ... Smallpox vaccine [DR:D05295] ... ICD-10: ...URNAL ... Dev Biol Stand 100:31-7 (1999) ... PMID:9795781 (description, env_factor) ... AUTHORS ... Ellner PD ... TITLE ... Smallpox

  6. Vaccination against meningitis B: is it worth it?

    Directory of Open Access Journals (Sweden)

    Peter English

    2013-01-01

    Full Text Available Summary: when a new vaccine is licensed having passed the tests for efficacy and safety, governments who have to pay for it to be used, as in the UK, will carry out a careful economic appraisal before making it generally available. In this challenging article, Dr Peter English discusses whether or not a new vaccine for meningitis that has just been licensed and that could save lives is actually worth it.

  7. Clinical Trials of an Experimental Ebola Vaccine: A Canadian ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This initiative supports phases 2 and 3 clinical trials of an experimental Ebola vaccine. The experimental vaccine is based on an attenuated recombinant Vesicular Stomatitis Virus vector (VSV-EBOV). The Public Health Agency of Canada developed the vaccine and licensed it to NewLink Genetics and Merck. Early vaccine ...

  8. A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers

    Energy Technology Data Exchange (ETDEWEB)

    Manish M Patel, Alan P Janssen, Richard Tardif, Mark Herring, Umesh Parashar

    2007-10-18

    In 2006, a new rotavirus vaccine (RotaTeq) was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield) was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.

  9. [The royal philanthropic expedition of the vaccine (Xavier de Balmis/Josep Salvany). 1803-1806].

    Science.gov (United States)

    Botet, Francesc Asensi

    2009-12-01

    Six years after Jenner discovered the anti-smallpox vaccine, King Charles IV mandated the initiation of vaccination campaigns throughout his kingdom. The overseas campaign was coordinated by the Valencian military doctor Xavier de Balmis with the aid of the Catalan Josep Salvany. The vaccine was transported to America "in vivo" in 22 children. The expedition departed from La Coruña on November 1806 and arrived to the Venezuelan port of La Guayra where it was split in two: One sub expedition under the order of Josep Salvany, continued by land to Colombia, Ecuador, Peru and Bolivia. Salvany died in the Bolivian city of Cochabamba. The other sub expedition, leaded by Balmis himself, continued by sea to Cuba and Mexico. From Acapulco it arrived to Manila and from there to Macau followed by inland penetration into China.

  10. Disease, religion and medicine: smallpox in nineteenth-century Benin Doenças, religião e medicina: a varíola no Benim, século XIX

    Directory of Open Access Journals (Sweden)

    Elisée Soumonni

    2012-12-01

    Full Text Available The essay examines, with special reference to smallpox, the perception and interpretation of disease in pre-colonial Dahomey, present-day Republic of Benin. Because disease is seen primarily as a punishment from the gods and not just as a medical problem or a bodily disorder, traditional cult priests play a leading role in making diagnoses and prescribing remedies, mostly based on medicinal plants. The prominence of Sakpata, god of smallpox, coupled with the influence of its priests is evaluated within the context of Dahomey's political history and the spread of the disease. This pivotal position was to constitute a challenge to the French colonial campaign to vaccinate against smallpox.O ensaio examina - com especial atenção à varíola - as percepções e interpretações das doenças no Daomé pré-colonial, atual República do Benim. Uma vez que as doenças eram vistas antes de tudo como punição divina, e não como problema ou distúrbio do corpo, os sacerdotes tradicionais exerciam papel central no seu diagnóstico e na prescrição de remédios, com base principalmente em plantas medicinais. A importância do culto a Sakpata, deus da varíola, juntamente com a influência dos sacerdotes é avaliada dentro do contexto da história política do Daomé e da disseminação das doenças. A posição crucial desse culto constituiu-se como um desafio para a campanha colonial francesa de vacinação contra a varíola.

  11. Newer Vaccines against Mosquito-borne Diseases.

    Science.gov (United States)

    Aggarwal, Anju; Garg, Neha

    2018-02-01

    Mosquitos are responsible for a number of protozoal and viral diseases. Malaria, dengue, Japanese encephalitis (JE) and chikungunya epidemics occur commonly all over the world, leading to marked mortality and morbidity in children. Zika, Yellow fever and West Nile fever are others requiring prevention. Environmental control and mosquito bite prevention are useful in decreasing the burden of disease but vaccination has been found to be most cost-effective and is the need of the hour. RTS,S/AS01 vaccine is the first malaria vaccine being licensed for use against P. falciparum malaria. Dengvaxia (CYD-TDV) against dengue was licensed first in Mexico in 2015. A Vero-cell derived, inactivated and alum-adjuvanted JE vaccine based on the SA14-14-2 strain was approved in 2009 in North America, Australia and various European countries. It can be used from 2 mo of age. In India, immunization is carried out in endemic regions at 1 y of age. Another inactivated Vero-cell culture derived Kolar strain, 821564XY, JE vaccine is being used in India. Candidate vaccines against dengue, chikungunya and West Nile fever are been discussed. A continued research and development of new vaccines are required for controlling these mosquito-borne diseases.

  12. Vaccinations against smallpox and tuberculosis are associated with better long-term survival

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Sørup, Signe

    2017-01-01

    to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42). CONCLUSIONS: Vaccinia and BCG vaccinations were associated...

  13. Jennerian vaccination and the creation of a national public health agenda in Japan, 1850-1900.

    Science.gov (United States)

    Jannetta, Ann

    2009-01-01

    Vaccination played a leading role in transforming the social and political status of medicine in Japanese society in the second half of the nineteenth century. The process began well before the Meiji Restoration of 1868 created a centralized government under the Japanese emperor. At the beginning of the century, medicine was a private business. There was no oversight from an interested government, and there were no medical societies or journals in which to debate and formulate opinion about medical practice. Medical knowledge was transmitted privately through personal lineage structures whose members jealously guarded their medical techniques. For almost a half century before live vaccine could be imported, knowledge of vaccination was limited to a small group of Japanese physicians who could read Dutch. This special knowledge created a medical elite whose members managed the transmission of vaccination after the vaccine arrived, and dominated the new medical and public health bureaucracies created by the Meiji state. By the end of the century, a rigorous vaccination program was in place, smallpox mortality had fallen, and Japan's Western-oriented physicians were in control of a national public health bureaucracy that could monitor the vaccination status of individuals in households throughout Japan.

  14. Safety of human papillomavirus vaccines: a review

    OpenAIRE

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-01-01

    Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage ra...

  15. 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.

  16. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

    Czech Academy of Sciences Publication Activity Database

    Stittelaar, K. J.; Neyts, J.; Naesens, L.; Amerongen van, G.; Lavieren van, R. F.; Holý, Antonín; De Clercq, E.; Niesters, H. G. M.; Fries, E.; Maas, Ch.; Mulder, P. G. H.; Zeijst van der, B. A. M.; Osterhaus, D. M. E.

    2006-01-01

    Roč. 439, č. 7077 (2006), s. 745-748 ISSN 0028-0836 Institutional research plan: CEZ:AV0Z40550506 Keywords : monkeypox virus * vaccination * HPMPC * HPMPO-DAPy Subject RIV: CC - Organic Chemistry Impact factor: 26.681, year: 2006

  17. Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development.

    Science.gov (United States)

    Pinto, Ligia A; Dillner, Joakim; Beddows, Simon; Unger, Elizabeth R

    2018-01-17

    When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials. Copyright © 2018 Elsevier Ltd. All rights

  18. Vaccination and the TAP-independent antigen processing pathways.

    Science.gov (United States)

    López, Daniel; Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen

    2013-09-01

    The cytotoxic CD8(+) T lymphocyte-mediated cellular response is important for the elimination of virus-infected cells and requires the prior recognition of short viral peptide antigens previously translocated to the endoplasmic reticulum by the transporter associated with antigen processing (TAP). However, individuals with nonfunctional TAP complexes or infected cells with TAP molecules blocked by specific viral proteins, such as the cowpoxvirus, a component of the first source of early empirical vaccination against smallpox, are still able to present several HLA class I ligands generated by the TAP-independent antigen processing pathways to specific cytotoxic CD8(+) T lymphocytes. Currently, bioterrorism and emerging infectious diseases have renewed interest in poxviruses. Recent works that have identified HLA class I ligands and epitopes in virus-infected TAP-deficient cells have implications for the study of both the effectiveness of early empirical vaccination and the analysis of HLA class I antigen processing in TAP-deficient subjects.

  19. Efficacy, safety and effectiveness of licensed rotavirus vaccines: a systematic review and meta-analysis for Latin America and the Caribbean.

    Science.gov (United States)

    Velázquez, Raúl F; Linhares, Alexandre C; Muñoz, Sergio; Seron, Pamela; Lorca, Pedro; DeAntonio, Rodrigo; Ortega-Barria, Eduardo

    2017-01-13

    RotaTeq™ (RV5; Merck & Co. Inc., USA) and Rotarix™ (RV1, GlaxoSmithKline, Belgium) vaccines, developed to prevent rotavirus diarrhea in children under five years old, were both introduced into national immunization programs in 2006. As many countries in Latin America and the Caribbean have included either RV5 or RV1 in their routine childhood vaccination programs, we conducted a systematic review and meta-analysis to analyze efficacy, safety and effectiveness data from the region. We conducted a systematic search in PubMed, EMBASE, Scielo, Lilacs and the Cochrane Central Register, for controlled efficacy, safety and effectiveness studies published between January 2000 until December 2011, on RV5 and RV1 across Latin America (where both vaccines are available since 2006). The primary outcome measures were: rotavirus-related gastroenteritis of any severity; rotavirus emergency department visits and hospitalization; and severe adverse events. The results of the meta-analysis for efficacy show that RV1 reduced the risk of any-severity rotavirus-related gastroenteritis by 65% (relative risk (RR) 0.35, 95% confidence interval (CI) 0.25; 0.50), and of severe gastroenteritis by 82% (RR 0.18, 95%CI 0.12; 0.26) versus placebo. In trials, both vaccines significantly reduced the risk of hospitalization and emergency visits by 85% (RR 0.15, 95%CI 0.09; 0.25) for RV1 and by 90% (RR 0.099, 95%CI 0.012; 0.77) for RV5. Vaccination with RV5 or RV1 did not increase the risk of death, intussusception, or other severe adverse events which were previously associated with the first licensed rotavirus vaccine. Real-world effectiveness studies showed that both vaccines reduced rotavirus hospitalization in the region by around 45-50% for RV5 (for 1 to 3 doses, respectively), and, by around 50-80% for RV1 (for 1 to 2 doses, respectively). For RV1, effectiveness against hospitalization was highest (around 80-96%) for children vaccinated before 12 months of age, compared with 5

  20. 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

  1. 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

  2. Updates on the web-based VIOLIN vaccine database and analysis system.

    Science.gov (United States)

    He, Yongqun; Racz, Rebecca; Sayers, Samantha; Lin, Yu; Todd, Thomas; Hur, Junguk; Li, Xinna; Patel, Mukti; Zhao, Boyang; Chung, Monica; Ostrow, Joseph; Sylora, Andrew; Dungarani, Priya; Ulysse, Guerlain; Kochhar, Kanika; Vidri, Boris; Strait, Kelsey; Jourdian, George W; Xiang, Zuoshuang

    2014-01-01

    The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.

  3. Vaccines Through Centuries: Major Cornerstones of Global Health

    Directory of Open Access Journals (Sweden)

    Inaya eHajj Hussein

    2015-11-01

    Full Text Available Multiple cornerstones have shaped the history of vaccines, which may contain live attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response.The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the 18th century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on small pox.The 19th century was a major landmark, with the Germ Theory of disease of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for BCG, Polio, DTP, measles, yellow fever and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010 The Decade of vaccines was launched, and on April 1st 2012, the United Nations launched the shot@Life campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated

  4. 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

  5. Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

    Science.gov (United States)

    Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

    2014-12-12

    A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Smallpox in the modern scientific and colonial contexts 1721–1840

    Indian Academy of Sciences (India)

    2011-09-23

    Sep 23, 2011 ... Home; Journals; Journal of Biosciences; Volume 36; Issue 5. Smallpox in the modern scientific and colonial contexts 1721–1840. Rajesh Kochhar. Perspectives Volume 36 Issue 5 December 2011 pp 761-768. Fulltext. Click here to view fulltext PDF. Permanent link:

  7. Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro®) and a varicella vaccine (VARIVAX®) by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial

    OpenAIRE

    Thomas Stéphane; Habermehl Pirmin; Gillet Yves; Eymin Cécile; Fiquet Anne

    2009-01-01

    Abstract Background When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro®) and a varicella vaccine (VARIVAX®) compared with the subcutaneous route. Methods An open-label random...

  8. Current strategic thinking for the development of a trivalent alphavirus vaccine for human use.

    Science.gov (United States)

    Wolfe, Daniel N; Heppner, D Gray; Gardner, Shea N; Jaing, Crystal; Dupuy, Lesley C; Schmaljohn, Connie S; Carlton, Kevin

    2014-09-01

    Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure. © The American Society of Tropical Medicine and Hygiene.

  9. Characterization of Two Historic Smallpox Specimens from a Czech Museum

    Czech Academy of Sciences Publication Activity Database

    Pajer, P.; Dresler, J.; Kabickova, H.; Píša, L.; Aganov, P.; Fucik, K.; Elleder, Daniel; Hron, Tomáš; Kuželka, V.; Velemínský, P.; Klimentová, J.; Fučíková, A.; Pejchal, J.; Hrabáková, Rita; Beneš, V.; Rausch, T.; Dundr, P.; Pilin, A.; Čabala, R.; Hubálek, Martin; Stříbrný, J.; Antwerpen, M.H.; Meyer, H.

    2017-01-01

    Roč. 9, č. 8 (2017), č. článku 200. ISSN 1999-4915 Institutional support: RVO:68378050 ; RVO:67985904 ; RVO:61388963 Keywords : smallpox * variola virus * evolution * next generation suquencing * historic specimen * phylogeny Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Virology; Virology (UZFG-Y); Virology (UOCHB-X) Impact factor: 3.465, year: 2016

  10. Active and passive immunity, vaccine types, excipients and licensing.

    Science.gov (United States)

    Baxter, David

    2007-12-01

    Abstract Immunity is the state of protection against infectious disease conferred either through an immune response generated by immunization or previous infection or by other non-immunological factors. This article reviews active and passive immunity and the differences between them: it also describes the four different commercially available vaccine types (live attenuated, killed/inactivated, subunit and toxoid): it also looks at how these different vaccines generate an adaptive immune response.

  11. Addressing a Yellow Fever Vaccine Shortage - United States, 2016-2017.

    Science.gov (United States)

    Gershman, Mark D; Angelo, Kristina M; Ritchey, Julian; Greenberg, David P; Muhammad, Riyadh D; Brunette, Gary; Cetron, Martin S; Sotir, Mark J

    2017-05-05

    Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

  12. A review of the literature on the economics of vaccination against TB

    NARCIS (Netherlands)

    Tu, H.A.; Vu, H.D.; Rozenbaum, M.H.; Woerdenbag, H.J.; Postma, M.J.

    The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in

  13. Bioterrorism and Smallpox: Policies, Practices, and Implications for Social Work

    Science.gov (United States)

    Mackelprang, Romel W.; Mackelprang, Romel D.; Thirkill, Ashley D.

    2005-01-01

    Terrorist acts and the fear of terrorism have become a part of everyday life in the early 21st century. Among the threats most feared is bioterrorism, including the intentional release of smallpox. With the invasion of Iraq and toppling of the Saddam Hussein regime, acute bioterrorism fears have abated; however, an ongoing threat remains. This…

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. Studies of parvovirus vaccination in the dog: the performance of live attenuated feline parvovirus vaccines.

    Science.gov (United States)

    Thompson, H; McCandlish, I A; Cornwell, H J; Macartney, L; Maxwell, N S; Weipers, A F; Wills, I R; Black, J A; Mackenzie, A C

    1988-04-16

    The performance of three live attenuated feline parvovirus vaccines licensed for use in the dog was studied. At the end of the primary vaccination course 67 per cent of dogs had inadequate antibody levels (less than or equal to 32) as measured by a haemagglutination inhibition test. Interference by maternal antibody accounted for some of the failures but the fact that there was no significant difference in performance between dogs vaccinated at 12 weeks or 16 weeks of age indicated that maternal antibody was not the only factor.

  19. The dichotomy of pathogens and allergens in vaccination approaches

    Directory of Open Access Journals (Sweden)

    Fiona J. Baird

    2014-07-01

    Full Text Available Traditional prophylactic vaccination to prevent illness is the primary objective of many research activities worldwide. The golden age of vaccination began with an approach called variolation in ancient China and the evolution of vaccines still continues today with modern developments such as the production of Gardasil™ against HPV and cervical cancer. The historical aspect of how different forms of vaccination have changed the face of medicine and communities is important as it dictates our future approaches on both a local and global scale. From the eradication of smallpox to the use of an experimental vaccine to save a species, this review will explore these successes in infectious disease vaccination and also discuss a few significant failures which have hampered our efforts to eradicate certain diseases. The second part of the review will explore designing a prophylactic vaccine for the growing global health concern that is allergy. Allergies are an emerging global health burden. Of particular concern is the rise of food allergies in developed countries where 1 in 10 children is currently affected. The formation of an allergic response results from the recognition of a foreign component by our immune system that is usually encountered on a regular basis. This may be a dust-mite or a prawn but this inappropriate immune response can result in a life-time of food avoidance and lifestyle restrictions. These foreign components are very similar to antigens derived from infectious pathogens. The question arises: should the allergy community be focussing on protective measures rather than ongoing therapeutic interventions to deal with these chronic inflammatory conditions? We will explore the difficulties and benefits of prophylactic vaccination against various allergens by means of genetic technology that will dictate how vaccination against allergens could be utilised in the near future.

  20. 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

  1. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Challenges of a Dengue Vaccine.

    Science.gov (United States)

    Screaton, Gavin; Mongkolsapaya, Juthathip

    2017-07-17

    A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  2. Safety and effectiveness of MF-59 adjuvanted influenza vaccines in children and adults.

    Science.gov (United States)

    Black, Steven

    2015-06-08

    The squalene oil-in-water emulsion MF-59 adjuvant was developed initially to enhance the immunogenicity of influenza vaccines in populations such as children and adults with known suboptimal response. Developed in the 1990s, it was initially licensed in Europe for use in seasonal influenza vaccine in the elderly. Since that time, both Avian and p2009H1N1 vaccines have also been developed. Overall, more than 30,000 individuals have participated in clinical trials of MF-59 adjuvanted vaccine and more than 160 million doses of licensed vaccine have been administered. Safety and effectiveness data from clinical trials and observation studies attest to the safety of MF-59 and to its ability to enhance the effectiveness of influenza vaccines in children and the elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. [Safety data of the new, reduced-dose influenza vaccine FluArt after its first season on the market].

    Science.gov (United States)

    Vajó, Péter; Gyurján, Orsolya; Szabó, Ágnes Mira; Kalabay, László; Vajó, Zoltán; Torzsa, Péter

    2017-12-01

    The currently licensed seasonal influenza vaccines contain split, subunit or whole virions, typically in amounts of 15 µg hemagglutinin per virus strain for adult and up to 60 µg in elderly patients. The present study reports safety data of the newly licensed, reduced dose vaccine with 6 µg of hemagglutinin per strain produced by Fluart (Hungary) after its first season on the market. The main objective of enhanced safety surveillance was to detect a potential increase in reactogenicity and allergic events that is intrinsic to the product in near real-time in the earliest vaccinated cohorts. The study methods were based on the Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU by the European Medicines Agency. We used the Fisher exact test with 95% confidence intervals. We studied 587 patients and detected a total 24 adverse events, all of which have already been known during the licensing studies of the present vaccine. The frequencies of the adverse events were not different from what had been seen with the previously licensed 15 µg vaccine. Based on the results, the authors conclude that the new, reduced dose vaccine FluArt is safe and tolerable. Orv Hetil. 2017; 158(49): 1953-1959.

  4. 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.

  5. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Jun-liang Yuan

    2016-01-01

    Full Text Available Acute disseminated encephalomyelitis (ADEM is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM.

  6. The Evolution of the Meningitis Vaccine Project.

    Science.gov (United States)

    Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F Marc

    2015-11-15

    In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public-private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  7. Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine.

    Science.gov (United States)

    Giuntini, Serena; Beernink, Peter T; Granoff, Dan M

    2015-12-16

    FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FH(high)), and six with FH(low) baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FH(low) baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FH(high) phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (pb deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FH(low) baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FH(high), the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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 .

  9. Vaccination against acute respiratory virus infections and measles in man.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); P. de Vries (Petra)

    1992-01-01

    textabstractSeveral viruses may cause more or less severe acute respiratory infections in man, some of which are followed by systemic infection. Only for influenza and measles are licensed vaccines available at present. The protection induced by influenza vaccines, which are based on inactivated

  10. Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan.

    Science.gov (United States)

    Shimizu, Hiroyuki

    2016-04-07

    During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Value of post-licensure data on benefits and risks of vaccination to inform vaccine policy: The example of rotavirus vaccines.

    Science.gov (United States)

    Parashar, Umesh D; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin; Yen, Catherine; Tate, Jacqueline E

    2015-11-27

    In 1999, the first rhesus-human reassortant rotavirus vaccine licensed in the United States was withdrawn within a year of its introduction after it was linked with intussusception at a rate of ∼1 excess case per 10,000 vaccinated infants. While clinical trials of 60,000-70,000 infants of each of the two current live oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), did not find an association with intussusception, post-licensure studies have documented a risk in several high and middle income countries, at a rate of ∼1-6 excess cases per 100,000 vaccinated infants. However, considering this low risk against the large health benefits of vaccination that have been observed in many countries, including in countries with a documented vaccine-associated intussusception risk, policy makers and health organizations around the world continue to support the routine use of RV1 and RV5 in national infant immunization programs. Because the risk and benefit data from affluent settings may not be directly applicable to developing countries, further characterization of any associated intussusception risk following rotavirus vaccination as well as the health benefits of vaccination is desirable for low income settings. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

  12. 78 FR 18354 - Government-Owned Inventions; Availability for Licensing

    Science.gov (United States)

    2013-03-26

    ... the viral genome without inactivating the virus. Competitive Advantages: Most of the HEV vaccines... photoresist masks to make feature sizes below 20nm. Competitive Advantages: Improved ultrafine imaging... licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results...

  13. Military Infectious Diseases Update on Vaccine Development

    Science.gov (United States)

    2011-01-24

    Licensed live vaccines (polio, MMR) - Radiation- attenuated sporozoites - Genetically- attenuated sporozoites 2011 MHS Conference Whole Organism...Not sufficiently attenuated Seattle Biomedical , Gates Foundation, WEHI and USMMVP 2011 MHS Conference Subunit approach- RTS,S Vaccine RTS,S is...Ad Boost  DNA plasmids [Prime] – Encoding malaria proteins CSP and AMA1  Adenovirus 5 ( attenuated )[Boost] – Encoding malaria proteins CSP and AMA1

  14. Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

    Science.gov (United States)

    Vannice, Kirsten S; Wilder-Smith, Annelies; Barrett, Alan D T; Carrijo, Kalinka; Cavaleri, Marco; de Silva, Aravinda; Durbin, Anna P; Endy, Tim; Harris, Eva; Innis, Bruce L; Katzelnick, Leah C; Smith, Peter G; Sun, Wellington; Thomas, Stephen J; Hombach, Joachim

    2018-03-07

    Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Global challenges of implementing human papillomavirus vaccines

    Directory of Open Access Journals (Sweden)

    Mishra Amrita

    2011-06-01

    Full Text Available Abstract Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.

  16. Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

    Science.gov (United States)

    Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2015-09-01

    The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50 % infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, were 2.7 ± 0.4 log10 p.f.u. for ICR mice and 3.5 ± 0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans.

  17. Protection of Mice from Lethal Vaccinia Virus Infection by Vaccinia Virus Protein Subunits with a CpG Adjuvant

    Directory of Open Access Journals (Sweden)

    Sarah Reeman

    2017-12-01

    Full Text Available Smallpox vaccination carries a high risk of adverse events in recipients with a variety of contra-indications for live vaccines. Although alternative non-replicating vaccines have been described in the form of replication-deficient vaccine viruses, DNA vaccines, and subunit vaccines, these are less efficacious than replicating vaccines in animal models. DNA and subunit vaccines in particular have not been shown to give equivalent protection to the traditional replicating smallpox vaccine. We show here that combinations of the orthopoxvirus A27, A33, B5 and L1 proteins give differing levels of protection when administered in different combinations with different adjuvants. In particular, the combination of B5 and A27 proteins adjuvanted with CpG oligodeoxynucleotides (ODN gives a level of protection in mice that is equivalent to the Lister traditional vaccine in a lethal vaccinia virus challenge model.

  18. Update on the use of meningococcal serogroup C CRM₁₉₇-conjugate vaccine (Meningitec) against meningitis.

    Science.gov (United States)

    Badahdah, Al-Mamoon; Rashid, Harunor; Khatami, Ameneh

    2016-01-01

    Meningitec is a CRM197-conjugated meningococcal serogroup C (MenC) vaccine, first licensed in 1999. It has been used as a primary and booster vaccine in infants, toddlers, older children and adults, and has been shown to be immunogenic and well-tolerated in all age groups, including premature infants. Vaccine effectiveness has been demonstrated using combined data on all three licensed MenC conjugate vaccines. Evidence from clinical trials, however, suggests that the different MenC conjugate vaccines behave differently with respect to the induction and persistence of bactericidal antibody and generation of immune memory. It appears that Meningitec has a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines. Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus on Meningitec.

  19. The origins of the vaccine cold chain and a glimpse of the future.

    Science.gov (United States)

    Lloyd, John; Cheyne, James

    2017-04-19

    International efforts to eradicate smallpox in the 1960s and 1970s provided the foundation for efforts to expand immunization programmes, including work to develop immunization supply chains. The need to create a reliable system to keep vaccines cold during the lengthy journey from the manufacturer to the point of use, even in remote areas, was a crucial concern during the early days of the Expanded Programme on Immunization. The vaccine cold chain was deliberately separated from other medical distribution systems to assure timely access to and control of vaccines and injection materials. The story of the early development of the vaccine cold chain shows how a number of challenges were overcome with technological and human resource solutions. For example, the lack of methods to monitor exposure of vaccines to heat during transport and storage led to many innovations, including temperature-sensitive vaccine vial monitors and better methods to record and communicate temperatures in vaccine stores. The need for appropriate equipment to store and transport vaccines in tropical developing countries led to innovations in refrigeration equipment as well as the introduction and widespread adoption of novel high performance vaccine cold-boxes and carriers. New technologies also helped to make injection safer. Underlying this work on technologies and equipment was a major effort to develop the human resources required to manage and implement the immunization supply chain. This included creating foundational policies and a management infrastructure; providing training for managers, health workers, technicians, and others. The vaccine cold chain has contributed to one of the world's public health success stories and provides three priority lessons for future: the vaccine supply chain needs to be integrated with other public health supplies, re-designed for efficiency and effectiveness and work is needed in the longer term to eliminate the need for refrigeration in the supply

  20. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

    Science.gov (United States)

    Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

    2017-08-23

    Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

  1. Rotavirus Vaccines: a story of success with challenges ahead

    Science.gov (United States)

    O’Ryan, Miguel

    2017-01-01

    Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries. PMID:28928954

  2. Mumps vaccine virus strains and aseptic meningitis.

    Science.gov (United States)

    Bonnet, Marie-Claude; Dutta, Anil; Weinberger, Clement; Plotkin, Stanley A

    2006-11-30

    Mumps immunization can easily be included in national schedules, particularly if combined with measles or measles and rubella vaccines, but debate continues concerning the relative safety of various licensed mumps vaccine strains. The opportunities for control of mumps are also being affected by differences in the cost of the vaccines prepared with different strains of mumps virus. The present report evaluates available data on the association of the Urabe and other strains of mumps vaccine with the occurrence of aseptic meningitis. We also review the comparative immunogenicity and efficacies of the most widely used mumps vaccines in controlled clinical trials and field evaluations, and briefly examine relative cost as it relates to the implementation of national immunization programs. We conclude that extensive experience with the most widely used mumps vaccine strains in many countries has shown that the risk-benefit ratio of live mumps vaccines is highly favourable for vaccination, despite the occasional occurence of aseptic meningitis.

  3. Microneedle and mucosal delivery of influenza vaccines

    Science.gov (United States)

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

    2017-01-01

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

  4. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    Full Text Available Smallpox, caused by variola virus (VARV, is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  5. Preventing the return of smallpox: molecular modeling studies on thymidylate kinase from Variola virus.

    Science.gov (United States)

    Guimarães, Ana Paula; Ramalho, Teodorico Castro; França, Tanos Celmar Costa

    2014-01-01

    Smallpox was one of the most devastating diseases in the human history and still represents a serious menace today due to its potential use by bioterrorists. Considering this threat and the non-existence of effective chemotherapy, we propose the enzyme thymidylate kinase from Variola virus (VarTMPK) as a potential target to the drug design against smallpox. We first built a homology model for VarTMPK and performed molecular docking studies on it in order to investigate the interactions with inhibitors of Vaccinia virus TMPK (VacTMPK). Subsequently, molecular dynamics (MD) simulations of these compounds inside VarTMPK and human TMPK (HssTMPK) were carried out in order to select the most promising and selective compounds as leads for the design of potential VarTMPK inhibitors. Results of the docking and MD simulations corroborated to each other, suggesting selectivity towards VarTMPK and, also, a good correlation with the experimental data.

  6. Vaccines and IP Rights: A Multifaceted Relationship.

    Science.gov (United States)

    Durell, Karen

    2016-01-01

    Just as there are many forms of vaccines and components to vaccines-particular compositions, delivery systems, components, and distribution networks-there are a variety of intellectual property (IP) protections applicable for vaccines. IP rights such as patent, copyright, trademarks, plant breeders' rights, and trade secrets may all be applicable to vaccines. Thus, discussion of IP rights and vaccines should not begin and end with the application of one IP right to a vaccine. The discussion should engage considerations of multiple IP rights applicable to a vaccine and how these can be utilized in an integrated manner in a strategy aimed at supporting the development and distribution of the vaccine. Such an approach to IP rights to vaccines allows for the integrated rights to be considered in light of the justifications for protecting vaccines with IP rights, as well as the issues relating to specific IP rights for vaccines, such as compulsory license regimes, available humanitarian purpose IP credits, etc. To view vaccines as the subject of multiple IP protections involves a refocusing, but the outcome can provide significant benefits for vaccine development and distribution.

  7. LGBT health and vaccinations: Findings from a community health survey of Lexington-Fayette County, Kentucky, USA.

    Science.gov (United States)

    Jones, Jeff; Poole, Asheley; Lasley-Bibbs, Vivian; Johnson, Mark

    2016-04-07

    Data on adult immunization coverage at the state level and for LGBT Americans in particular are sparse. This study reports the results of a 2012 Lexington-Fayette County, Kentucky, community health assessment's results asking about eight adult vaccinations among 218 lesbian, gay, bisexual, and transgendered (LGBT) respondents. Researchers collected data using an online survey distributed through LGBT social media, posters, and LGBT print media. The LGBT sample largely matches the demographics of the county as a whole except this group reports higher level of education and fewer uninsured individuals. Among LGBT respondents, immunization prevalence reaches 68.0% (annual Influenza), 65.7% (Hepatitis B), 58.8% (Chickenpox/Varicella), 55.9% (Hepatitis A), 41.2% (Smallpox), and 25.8% (Pneumonia). Among respondents who are currently within the recommended 19-26 years age range for the Human Papillomavirus (HPV) vaccine, the LGBT females are less likely to report receiving the vaccine (15.4%) compared to the national coverage percentage of 34.5%. Males, however, are more likely to have received the vaccine (10.3%) than the national percentage of 2.3%. The small number of LGBT seniors in the study report a much higher prevalence of the Shingles (Herpes Zoster) vaccines than for U.S. seniors 60 and older (71.4% compared to 20.1% nationally). LGBT respondents report higher percentages of adult vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. A cross-sectional study of HPV vaccine acceptability in Gaborone, Botswana.

    Directory of Open Access Journals (Sweden)

    Yumi Taylor DiAngi

    Full Text Available BACKGROUND: Cervical cancer is the most common cancer among women in Botswana and elsewhere in Sub-Saharan Africa. We sought to examine whether HPV vaccine is acceptable among parents in Botswana, which recently licensed the vaccine to prevent cervical cancer. METHODS AND FINDINGS: We conducted a cross-sectional survey in 2009, around the time the vaccine was first licensed, with adults recruited in general medicine and HIV clinics in Gaborone, the capital of Botswana. Although only 9% (32/376 of respondents had heard of HPV vaccine prior to the survey, 88% (329/376 said they definitely will have their adolescent daughters receive HPV vaccine. Most respondents would get the vaccine for their daughters at a public or community clinic (42% or a gynecology or obstetrician's office (39%, and 74% would get it for a daughter if it were available at her school. Respondents were more likely to say that they definitely will get HPV vaccine for their daughters if they had less education (OR = 0.20, 95% CI = 0.07-0.58 or lived more than 30 kilometers from the capital, Gaborone (OR = 2.29, 95% CI = 1.06-4.93. Other correlates of acceptability were expecting to be involved in the decision to get HPV vaccine, thinking the vaccine would be hard to obtain, and perceiving greater severity of HPV-related diseases. CONCLUSIONS: HPV vaccination of adolescent girls would be highly acceptable if the vaccine became widely available to the daughters of healthcare seeking parents in Gaborone, Botswana. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine as well as work to minimize barriers.

  9. Mass psychogenic illness after vaccination.

    Science.gov (United States)

    Clements, C John

    2003-01-01

    surveillance/reporting systems for reporting adverse events be improved before such campaigns. A mass campaign using a smallpox vaccine should be accompanied by a surveillance system capable of distinguishing between multiple cases of conventionally understood vaccine reactions and outbreaks of mass psychogenic illness.

  10. Steady progress toward a malaria vaccine.

    Science.gov (United States)

    Lyke, Kirsten E

    2017-10-01

    Great progress has been made in reducing malaria morbidity and mortality, yet the parasite continues to cause a startling 200 million infections and 500 000 deaths annually. Malaria vaccine development is pushing new boundaries by steady advancement toward a licensed product. Despite 50 years of research, the complexity of Plasmoidum falciparum confounds all attempts to eradicate the organism. This very complexity has pushed the boundaries of vaccine development to new heights, yet it remains to be seen if an affordable vaccine can provide durable and high-level protection. Novel vaccines such as RTS,S/AS01E are on the edge of licensure, but old techniques have resurged with the ability to deliver vialed, whole organism vaccines. Novel adjuvants, multistage/multiantigen approaches and transmission blocking vaccines all contribute to a multipronged battle plan to conquer malaria. Vaccines are the most cost-effective tools to control infectious diseases, yet the complexity of malaria has frustrated all attempts to develop an effective product. This review concentrates on recent advances in malaria vaccine development that lend hope that a vaccine can be produced and malaria eradicated.

  11. 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

  12. Genital Autoinoculation with Vaccinia: A Look at Two Cases.

    Science.gov (United States)

    Whittington, Julie R; Rollene, Nanette L; Gist, Richard S

    2018-05-01

    Smallpox, or vaccinia, has been eradicated worldwide as a disease; however, it may be weaponized and is thus a required immunization when military members deploy to certain parts of the world. We report two unusual cases of genital autoinoculation following smallpox vaccination. Both patients' lesions resolved without sequelae within 20 d. We advocate for thorough education on this potential vaccination adverse event. These cases highlight the importance of a broad differential diagnosis when dealing with vulvar lesions, particularly in our military population.

  13. Persistence of Meningococcal Antibodies and Response to a Third Dose After a Two-dose Vaccination Series with Investigational MenABCWY Vaccine Formulations in Adolescents.

    Science.gov (United States)

    Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Han, Linda; Smolenov, Igor; Dull, Peter

    2015-10-01

    In a primary study, healthy adolescents received 2 doses (months 0/2) of 1 of the 4 investigational meningococcal ABCWY vaccine formulations, containing components of licensed quadrivalent glycoconjugate vaccine MenACWY-CRM, combined with different amounts of recombinant proteins (rMenB) and outer membrane vesicles (OMV) from a licensed serogroup B vaccine, or 2 doses of rMenB alone or 1 dose of MenACWY-CRM then a placebo. This phase 2 extension study evaluated antibody persistence up to 10 months after the 2-dose series and the immunogenicity and safety of a third dose (month 6). Immune responses against serogroups ACWY and serogroup B test strains were measured by serum bactericidal assay with human complement. At month 12, antibody persistence against serogroups ACWY in all 2-dose MenABCWY groups was at least comparable with the 1-dose MenACWY-CRM group. Bactericidal antibodies against most serogroup B test strains declined by month 6, then plateaued over the subsequent 6 months, with overall higher antibody persistence associated with OMV-containing formulations. A third MenABCWY vaccine dose induced robust immune responses against vaccine antigens, although antibody levels 6 months later were comparable with those observed 5 months after the 2-dose series. All investigational MenABCWY vaccines were well tolerated. Two or three doses of investigational MenABCWY vaccines elicited immune responses against serogroups ACWY that were at least comparable with those after 1 dose of MenACWY-CRM. After either vaccination series, investigational MenABCWY vaccine formulations containing OMV had the highest immunogenicity against most serogroup B test strains. No safety concerns were identified in this study.

  14. 75 FR 60436 - Intent To Grant an Exclusive Field of Use License of U.S. Government-Owned Patents

    Science.gov (United States)

    2010-09-30

    ... DEPARTMENT OF DEFENSE Department of the Army Intent To Grant an Exclusive Field of Use License of U.S. Government-Owned Patents AGENCY: Department of the Army, DoD. ACTION: Notice. SUMMARY: In... of the intent to grant a field of use exclusive, revocable license for the field of vaccination of...

  15. De vreselijkste aller harpijen : pokkenepidemieen en pokkenbestrijding in Nederland in de achttiende en negentiende eeuw : een sociaal-historische en historisch-demografische studie

    NARCIS (Netherlands)

    Rutten, W.

    1997-01-01

    This study examines the fight against smallpox in the Netherlands in the 18th and 19th centuries. Smallpox mortality dropped in an unprecedented way from about 1810, generating a substantial reduction in the urban child mortality rate. The impact of vaccination on the acceleration of the Dutch

  16. Integrated Analysis of Genetic and Proteomic Data Identifies Biomarkers Associated with Adverse Events Following Smallpox Vaccination

    Science.gov (United States)

    Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experi...

  17. Rotavirus infection and the current status of rotavirus vaccines

    Directory of Open Access Journals (Sweden)

    Shou-Chien Chen

    2012-04-01

    Full Text Available Among children, rotaviruses are the most common cause of severe gastroenteritis worldwide and of diarrheal deaths in developing countries. Current vaccines (e.g., Rotarix, GlaxoSmithKline Biologicals; RotaTeq, Merck and Company effectively reduce rotaviral gastroenteritis, emergency department visits, and hospitalizations. The tremendous burden of rotavirus-related diarrhea in children across the world continues to drive the remarkable pace of vaccine development. This review assesses the global epidemiological and economic burden of rotavirus diseases, summarizes the relevant principles of the development of rotavirus vaccines, and presents data on the efficacy and effectiveness of currently licensed vaccines in both developed and developing countries.

  18. Trends in clinical trials of dengue vaccine

    Directory of Open Access Journals (Sweden)

    Priya Marimuthu

    2016-01-01

    Full Text Available Dengue is one of the most important vector-borne disease and an increasing problem worldwide because of current globalization trends. Roughly, half the world′s population lives in dengue endemic countries, and nearly 100 million people are infected annually with dengue. India has the highest burden of the disease with 34% of the global cases. In the context of an expanding and potentially fatal infectious disease without effective prevention or specific treatment, the public health value of a protective vaccine is clear. There is no licensed dengue vaccine is available still, but several vaccines are under development. Keeping in view the rise in dengue prevalence globally, there is a need to increase clinical drug and vaccine research on dengue. This paper briefly reviews on the development and current status of dengue vaccine to provide information to policymakers, researchers, and public health experts to design and implement appropriate vaccine for prophylactic intervention.

  19. Vaccination of horses with Lyme vaccines for dogs induces short-lasting antibody responses.

    Science.gov (United States)

    Guarino, Cassandra; Asbie, Sanda; Rohde, Jennifer; Glaser, Amy; Wagner, Bettina

    2017-07-24

    Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. Observational study on immune response to yellow fever and measles vaccines in 9 to 15-month old children. Is it necessary to wait 4 weeks between two live attenuated vaccines?

    Science.gov (United States)

    Michel, R; Berger, F; Ravelonarivo, J; Dussart, P; Dia, M; Nacher, M; Rogier, S; Moua, D; Sarr, F D; Diop, O M; Sall, A A; Baril, L

    2015-05-11

    The use of 2 live attenuated vaccines (LAV) is recommended to be simultaneous or after an interval of at least four weeks between injections. The primary objective of this study was to compare the humoral response to yellow fever (YF) and measles vaccines among children vaccinated against these two diseases, either simultaneously or separated by an interval of 7-28 days. A prospective, multicenter observational study was conducted among children aged 9-15 months. The primary endpoint was the occurrence of positive yellow fever antibodies after YF vaccine by estimating the titers of neutralizing antibodies from venous blood samples. Children vaccinated against YF 7-28 days after receiving the vaccine against measles (test group) were compared with children vaccinated the same day against these two diseases (referent group). Analysis was performed on 284 children. Of them, fifty-four belonged to the test group. Measles serology was positive in 91.7% of children. Neutralizing antibodies against YF were detected in 90.7% of the test group and 92.9 of the referent group (p=0.6). In addition, quantitative analysis of the immune response did not show a lower response to YF vaccination when it took place 1-28 days after measles vaccination. In 1965, Petralli showed a lower response to the smallpox vaccine when injected 4-20 days after measles vaccination. Since then, recommendations are to observe an interval of four weeks between LAV not injected on the same day. Other published studies failed to show a significant difference in the immune response to a LAV injected 1-28 days after another LAV. These results suggest that the usual recommendations for immunization with two LAV may not be correct. In low income countries, the current policy should be re-evaluated. This re-evaluation should also be applied to travelers to yellow fever endemic countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Need for a safe vaccine against respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Joo-Young Kim

    2012-09-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.

  2. Vaccines against enteric infections for the developing world

    Science.gov (United States)

    Czerkinsky, Cecil; Holmgren, Jan

    2015-01-01

    Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: —limited knowledge regarding the properties of the gut immune system during early life;—lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines;—lack of correlates/surrogates of mucosal immune protection; and—limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries.There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. PMID:25964464

  3. Dengue vaccines: Are they safe for travelers?

    Science.gov (United States)

    Halstead, Scott B; Aguiar, Maira

    2016-01-01

    The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries. An additional two dengue vaccines, developed by the National Institute of Allergy and Infectious Diseases (NIAID), USA and Takeda, are entering phase III testing. Dengvaxia is composed of four yellow fever 17D-DENV chimeras, the NIAID vaccine contains three mutagenized DENV and one DENV2/4 chimera while the Takeda vaccine contains an attenuated DENV 2 and three DENV 2-DENV chimeras. Which of these vaccines might be useful in protecting travelers against dengue infections and disease? Dengvaxia requires three doses administered over the course of one year but in addition has safety signals suggesting that susceptible individuals should not be vaccinated. The NIAID vaccine is promising as a travel vaccine as a single dose fully protected susceptible adults against live dengue 2 virus challenge. The protective efficacy and safety of the Takeda vaccine remain to be demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. A New Wave of Vaccines for Non-Communicable Diseases: What Are the Regulatory Challenges?

    Science.gov (United States)

    Darrow, Jonathan J; Kesselheim, Aaron S

    2015-01-01

    Vaccines represent one of the greatest achievements of medicine, dramatically reducing the incidence of serious or life-threatening infectious diseases and allowing people to live longer, healthier lives. As life expectancy has increased, however, the burden of non-communicable diseases (NCDs) such as cancer, hypertension, atherosclerosis, and diabetes has increased. This shifting burden of disease has heightened the already urgent need for therapies that treat or prevent NCDs, a need that is now being met with increased efforts to develop NCD vaccines. Like traditional vaccines, NCD vaccines work by modulating the human immune system, but target cells, proteins or other molecules that are associated with the NCD in question rather than pathogens or pathogen-infected cells. Efforts are underway to develop NCD vaccines to address not only cancer and hypertension, but also addiction, obesity, asthma, arthritis, psoriasis, multiple sclerosis, and Crohn's disease, among others. NCD vaccines present an interesting challenge for the U.S. Food and Drug Administration (FDA), which is tasked with approving new treatments on the basis of efficacy and safety. Should NCD vaccines be evaluated under the same analytic frame as traditional vaccines, or that of biologic drugs? Despite the borrowed nomenclature, NCD vaccines differ in important ways from infectious disease vaccines. Because infectious disease vaccines are generally administered to healthy individuals, often children, tolerance for adverse events is low and willingness to pay is limited. It is important to have infectious disease vaccines even for rare or eradicated disease (e.g., smallpox), in the event of an outbreak. The efficacy of infectious disease vaccines is generally high, and the vaccines convey population level benefits associated with herd immunity and potential eradication. The combination of substantial population-level benefits, low willingness to pay, and low tolerance for adverse events explains the

  5. 78 FR 42530 - Prospective Grant of an Exclusive License: Human Papillomavirus 16 E2 and E6 Peptides for...

    Science.gov (United States)

    2013-07-16

    ... peptide from HPV 16. E6 peptide vaccines are potentially prophylactic or therapeutic for cervical cancer... Exclusive License: Human Papillomavirus 16 E2 and E6 Peptides for Cervical Cancer Vaccine Development AGENCY... principal place of business in Augusta, Georgia. The United States of America is an assignee to the patent...

  6. Comment: Characterization of Two Historic Smallpox Specimens from a Czech Museum

    OpenAIRE

    Porter, Ashleigh F.; Duggan, Ana T.; Poinar, Hendrik N.; Holmes, Edward C.

    2017-01-01

    The complete genome sequences of two strains of variola virus (VARV) sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show...

  7. Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough.

    Science.gov (United States)

    Kapil, Parul; Papin, James F; Wolf, Roman F; Zimmerman, Lindsey I; Wagner, Leslie D; Merkel, Tod J

    2018-03-28

    Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at 6-8 weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease. We hypothesized that protection was due to toxin-neutralizing, maternal anti-pertussis toxin antibodies and predicted that maternal vaccination with a pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only vaccine were challenged with B. pertussis at 5 weeks of age and followed for infection and signs of disease. Although all challenged infants were heavily colonized, the infant baboons born to mothers vaccinated with PTx-only vaccine were free from clinical disease following exposure to B. pertussis. In contrast, disease was observed in infants born to unvaccinated mothers. Our results demonstrated that maternal vaccination with a PTx-only vaccine is sufficient to protect newborn baboons from disease following exposure to pertussis.

  8. Review of recent literature on microneedle vaccine delivery technologies

    Directory of Open Access Journals (Sweden)

    Vrdoljak A

    2013-08-01

    Full Text Available Anto Vrdoljak Development Laboratory, Genera, Rakov Potok, Croatia Abstract: Microneedles (MNs have been developed as medical devices for enhanced and painless transdermal drug and vaccine delivery. MN-based vaccine application, unlike conventional intramuscular or subcutaneous application using hypodermic needles, delivers vaccine directly into skin, which is known to be an immunologically much more relevant vaccination site than underlying tissue. Vaccination using MN devices targets the skin's rich immune system, leading to better utilization of the antigen and resulting in superior immune response, often achieved using a lower vaccine dose than required by conventional delivery routes. However, despite the number of advantages and nearly four decades of research, the number of licensed MN-based vaccines remains limited to date. Nevertheless, it is to be expected that on the back of a number of recently developed scalable and robust MN-fabrication methods, more intensive translation into clinical practice will follow. Here, we review the current status and trends in research of MN-related vaccine delivery platforms, focusing on the most promising approaches and clinically relevant applications. Keywords: microneedles, vaccine delivery, skin vaccination

  9. Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research

    Directory of Open Access Journals (Sweden)

    Mary G. Reynolds

    2017-12-01

    Full Text Available Monkeypox is a smallpox-like illness that can be accompanied by a range of significant medical complications. To date there are no standard or optimized guidelines for the clinical management of monkeypox (MPX patients, particularly in low-resource settings. Consequently, patients can experience protracted illness and poor outcomes. Improving care necessitates developing a better understanding of the range of clinical manifestations—including complications and sequelae—as well as of features of illness that may be predictive of illness severity and poor outcomes. Experimental and natural infection of non-human primates with monkeypox virus can inform the approach to improving patient care, and may suggest options for pharmaceutical intervention. These studies have traditionally been performed to address the threat of smallpox bioterrorism and were designed with the intent of using MPX as a disease surrogate for smallpox. In many cases this necessitated employing high-dose, inhalational or intravenous challenge to recapitulate the severe manifestations of illness seen with smallpox. Overall, these data—and data from biomedical research involving burns, superficial wounds, herpes, eczema vaccinatum, and so forth—suggest that MPX patients could benefit from clinical support to mitigate the consequences of compromised skin and mucosa. This should include prevention and treatment of secondary bacterial infections (and other complications, ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals. A standard of care that considers these factors should be developed and assessed in different settings, using clinical metrics specific for MPX alongside consideration of antiviral therapies.

  10. Safety of human papillomavirus vaccines: a review.

    Science.gov (United States)

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-05-01

    Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence.

  11. 75 FR 39668 - Intent To Grant a Field of Use Exclusive License of a U.S. Government-Owned Patent Application

    Science.gov (United States)

    2010-07-12

    ... DEPARTMENT OF DEFENSE Department of the Army Intent To Grant a Field of Use Exclusive License of a U.S. Government-Owned Patent Application AGENCY: Department of the Army, DoD. ACTION: Notice... intent to grant a field of use exclusive, revocable license for the field of shigella vaccine development...

  12. Human papillomavirus vaccination in the prevention of cervical neoplasia.

    LENUS (Irish Health Repository)

    Astbury, Katharine

    2012-02-01

    Cervical cancer remains a major cause of morbidity and mortality for women worldwide. Although the introduction of comprehensive screening programs has reduced the disease incidence in developed countries, it remains a major problem in the developing world. The recent licensing of 2 vaccines against human papillomavirus (HPV) type 16 and HPV-18, the viruses responsible for 70% of cervical cancer cases, offers the hope of disease prevention. In this article, we review the role of HPV in the etiology of cervical cancer and the evidence to support the introduction of vaccination programs in young women and discuss the potential obstacles to widespread vaccination. In addition, we discuss the issues that remain to be elucidated, including the potential need for booster doses of the vaccine and the role of concomitant vaccination in men.

  13. A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers

    Directory of Open Access Journals (Sweden)

    Herring Mark

    2007-10-01

    Full Text Available Abstract Background In 2006, a new rotavirus vaccine (RotaTeq was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. Methods We explored beliefs and attitudes of parents (n = 57 and providers (n = 10 towards rotavirus disease and vaccines through a qualitative assessment using focus groups and in-depth interviews. Results All physicians were familiar with safety concerns about rotavirus vaccines, but felt reassured by RotaTeq's safety profile. When asked about likelihood of using RotaTeq on a scale of one to seven (1 = "absolutely not;" 7 = "absolutely yes" the mean score was 5 (range = 3–6. Physicians expressed a high likelihood of adopting RotaTeq, particularly if recommended by their professional organizations and expressed specific interest in post-marketing safety data. Similarly, consumers found the RotaTeq safety profile to be favorable and would rely on their physician's recommendation for vaccination. However, when asked to rank likelihood of having their child vaccinated against rotavirus (1 = "definitely not get;" 7 = "definitely get", 29% ranked 1 or 2, 36% 3 or 4, and 35% 5 to 7. Conclusion Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.

  14. Current status and future prospects of yellow fever vaccines.

    Science.gov (United States)

    Beck, Andrew S; Barrett, Alan D T

    2015-01-01

    Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized historically for its immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be lifelong. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease.

  15. Current Status and Future Prospects of Yellow Fever Vaccines

    Science.gov (United States)

    Beck, Andrew S.; Barrett, Alan D.T.

    2017-01-01

    Summary Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized for historically immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be life-long. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease. PMID:26366673

  16. Meningococcal serogroup A, C, W₁₃₅ and Y conjugated vaccine: a cost-effectiveness analysis in the Netherlands

    NARCIS (Netherlands)

    Hepkema, Hiltsje; Pouwels, Koen B.; van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.

    2013-01-01

    In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY) was licensed for use in

  17. Vaccines against enteric infections for the developing world.

    Science.gov (United States)

    Czerkinsky, Cecil; Holmgren, Jan

    2015-06-19

    Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: -limited knowledge regarding the properties of the gut immune system during early life; -lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; -lack of correlates/surrogates of mucosal immune protection; and -limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  18. Phase 1 study of pandemic H1 DNA vaccine in healthy adults.

    Directory of Open Access Journals (Sweden)

    Michelle C Crank

    Full Text Available A novel, swine-origin influenza A (H1N1 virus was detected worldwide in April 2009, and the World Health Organization (WHO declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1 influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1 licensed monovalent inactivated vaccine (MIV.20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.Clinicaltrials.gov NCT00973895.

  19. Hendra and Nipah viruses: pathogenesis, animal models and recent breakthroughs in vaccination

    Directory of Open Access Journals (Sweden)

    Weingartl HM

    2015-09-01

    Full Text Available Hana M Weingartl National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada Abstract: Hendra and Nipah viruses are two highly pathogenic zoonotic members of the genus Henipavirus, family Paramyxoviridae, requiring work under biosafety level 4 conditions due to a lack of effective therapy and human vaccines. Several vaccine candidates were protective in animal models: recombinant vaccinia virus expressing Nipah virus (NiV F and G proteins in hamsters against NiV; recombinant ALVAC–NiV F and G in swine against NiV; recombinant Hendra virus (HeV soluble G protein (sGHeV against HeV and NiV in cats, ferrets, horses, and African green monkeys (AGM; recombinant vesicular stomatitis virus-based vectors expressing NiV F or G against NiV in hamsters and ferrets; measles virus-based NiV G vaccine candidate in hamsters and AGMs against NiV; and adenoassociated virus expressing NiG protein, which protected hamsters against NiV. The sGHeV was licensed for use in horses (Equivac HeV® in 2012. It is the first vaccine candidate licensed against a biosafety level 4 agent. With the development of suitable animal models (ferret, hamster and, importantly, AGM, progress can be made toward development of a human vaccine.Keywords: henipavirus, equine, swine, human infection, animal models, vaccine candidates

  20. [Demyelinating disease and vaccination of the human papillomavirus].

    Science.gov (United States)

    Álvarez-Soria, M Josefa; Hernández-González, Amalia; Carrasco-García de León, Sira; del Real-Francia, M Ángeles; Gallardo-Alcañiz, M José; López-Gómez, José L

    2011-04-16

    Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered. We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.

  1. 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

  2. Development and Regulation of Novel Influenza Virus Vaccines: A United States Young Scientist Perspective.

    Science.gov (United States)

    Khurana, Surender

    2018-04-27

    Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient. Low vaccine effectiveness of seasonal influenza vaccines in recent years provides an impetus to improve current seasonal influenza vaccines, and for development of next-generation influenza vaccines that can provide broader, long-lasting protection against both matching and antigenically diverse influenza strains. This review discusses a perspective on some of the issues and formidable challenges facing the development and regulation of the next-generation influenza vaccines.

  3. A libertarian case for mandatory vaccination.

    Science.gov (United States)

    Brennan, Jason

    2018-01-01

    This paper argues that mandatory, government-enforced vaccination can be justified even within a libertarian political framework. If so, this implies that the case for mandatory vaccination is very strong indeed as it can be justified even within a framework that, at first glance, loads the philosophical dice against that conclusion. I argue that people who refuse vaccinations violate the 'clean hands principle', a (in this case, enforceable) moral principle that prohibits people from participating in the collective imposition of unjust harm or risk of harm. In a libertarian framework, individuals may be forced to accept certain vaccines not because they have an enforceable duty to serve the common, and not because cost-benefit analysis recommends it, but because anti-vaxxers are wrongfully imposing undue harm upon others. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: Implications from other RNA viruses

    Directory of Open Access Journals (Sweden)

    Shoko eNishiyama

    2015-08-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae. Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the United States. MP-12 displays a temperature-sensitive (ts phenotype and does not replicate at 41oC. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF.

  5. [From the licensure of vaccines to the recommendation of the Standing Committee on Vaccination in Germany : criteria for the assessment of benefits and risks].

    Science.gov (United States)

    Pfleiderer, Michael; Wichmann, Ole

    2015-03-01

    Vaccines are among the most effective preventive measures in modern medicine and have led to a dramatic decline and-for a few diseases-even to the elimination of severely infectious diseases. There are some particularities of the risk-benefit assessment of vaccines compared with that of therapeutic drugs. These include the fact that vaccines are applied to healthy individuals with the aim of preventing an infectious disease, while therapeutic drugs are administered to sick people to cure them of an already acquired disease. The acceptable level of risk associated with the application of a vaccine is therefore much lower. In addition, high vaccination coverage can lead to population-level effects (e.g., the indirect protection of unvaccinated individuals) that can confer additional benefits to the population overall. When a marketing authorization application (MAA) for a novel vaccine is evaluated, conclusions are made regarding its quality, safety, and efficacy, and a benefit-risk assessment is carried out accordingly. In contrast, when deciding on the introduction of a new vaccine into a national immunization program or on a recommendation for a specific risk-group, the focus is shifted to considerations of how a licensed vaccine can be best used in a population (e.g., which immunization strategy is most effective in preventing deaths or hospitalizations, or in reducing treatment costs for the health care system). Stringent assessment criteria have been developed that require a robust safety analysis before a new vaccine is administered to humans for the first time in pre-licensure studies. Similarly, criteria are applied for calculating the benefit-risk ratio at the time of the licensure of a new vaccine in addition to during the entire post-licensure period. However, when deciding if and how a licensed vaccine can best be integrated into an existing immunization program, additional criteria are applied that are different, yet complementary to those applied for

  6. The Regulatory Evaluation of Vaccines for Human Use.

    Science.gov (United States)

    Baylor, Norman W

    2016-01-01

    A vaccine is an immunogen, the administration of which is intended to stimulate the immune system to result in the prevention, amelioration, or therapy of any disease or infection (US Food and Drug Administration. Guidance for Industry: content and format of chemistry, manufacturing, and controls information and establishment description information for a vaccine or related product). A vaccine may be a live attenuated preparation of microorganisms, inactivated (killed) whole organisms, living irradiated cells, crude fractions, or purified immunogens, including those derived from recombinant DNA in a host cell, conjugates formed by covalent linkage of components, synthetic antigens, polynucleotides (such as the plasmid DNA vaccines), living vectored cells expressing specific heterologous immunogens, or cells pulsed with immunogen. Vaccines are highly complex products that differ from small molecule drugs because of the biological nature of the source materials such as those derived from microorganisms as well as the various cell substrates from which some are derived. Regardless of the technology used, because of their complexities, vaccines must undergo extensive characterization and testing. Special expertise and procedures are needed for their manufacture, control, and regulation. The Food and Drug Administration (FDA) is the National Regulatory Authority (NRA) in the United States responsible for assuring quality, safety, and effectiveness of all human medical products, including vaccines for human use.The Center for Biologics Evaluation and Research (CBER) within the US FDA is responsible for overseeing the regulation of therapeutic and preventative vaccines against infectious diseases. Authority for the regulation of vaccines resides in Section 351 of the Public Health Service Act and specific sections of the Federal Food, Drug, and Cosmetic Act (FD&C). Vaccines are regulated as biologics and licensed based on the demonstration of safety and effectiveness. The

  7. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    OpenAIRE

    Warimwe, GM; Lorenzo, G; Lopez-Gil, E; Reyes-Sandoval, A; Cottingham, MG; Spencer, AJ; Collins, KA; Dicks, MD; Milicic, A; Lall, A; Furze, J; Turner, AV; Hill, AV; Brun, A; Gilbert, SC

    2013-01-01

    BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibod...

  8. Gold nanorod vaccine for respiratory syncytial virus

    International Nuclear Information System (INIS)

    Stone, John W; Thornburg, Natalie J; Blum, David L; Kuhn, Sam J; Crowe Jr, James E; Wright, David W

    2013-01-01

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response. (paper)

  9. Role and uptake of human papillomavirus vaccine in adolescent health in the United States

    Directory of Open Access Journals (Sweden)

    Sudenga SL

    2011-08-01

    Full Text Available Staci L Sudenga, Kathryn E Royse, Sadeep ShresthaDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: Both the prophylactic human papillomavirus (HPV vaccines, Gardasil® and Cervarix®, are licensed for the prevention of cervical cancer in females, and Gardasil is also licensed for the prevention of genital warts and anal cancer in both males and females. This review focuses on the uptake of these vaccines in adolescent males and females in the USA and the barriers associated with vaccine initiation and completion. In the USA in 2009, approximately 44.3% of adolescent females aged 13–17 years had received at least one dose of the HPV vaccine, but only 26.7% had received all three doses. In general, the Northeast and Midwest regions of the USA have the highest rates of HPV vaccine initiation in adolescent females, while the Southeast has the lowest rates of vaccine initiation. Uptake of the first dose of the HPV vaccine in adolescent females did not vary by race/ethnicity; however, completion of all three doses is lower among African Americans (23.1% and Latinos (23.4% compared with Caucasians (29.3%. At present, vaccination rates among adolescent females are lower than expected, and thus vaccine models suggest that it is more cost-effective to vaccinate both adolescent males and females. Current guidelines for HPV vaccination in adolescent males is recommended only for “permissive use,” which leaves this population out of routine vaccination for HPV. The uptake of the vaccine is challenged by the high cost, feasibility, and logistics of three-dose deliveries. The biggest impact on acceptability of the vaccine is by adolescents, physicians, parents, and the community. Future efforts need to focus on HPV vaccine education among adolescents and decreasing the barriers associated with poor vaccine uptake and completion in adolescents before their sexual debut, but Papanicolau

  10. 76 FR 66728 - Government-Owned Inventions; Licensing and Collaborative Research Opportunity for PANVAC-Cancer...

    Science.gov (United States)

    2011-10-27

    ... identification of molecular targets associated with cancer, the focus of drug development has shifted from... Immunology and Biology, Center for Cancer Research, NCI. The CRADA partner will (a) generate and characterize...; Licensing and Collaborative Research Opportunity for PANVAC--Cancer Vaccine for the Prevention and Treatment...

  11. "A wild and wondrous ride": CDC field epidemiologists in the east Pakistan smallpox and cholera epidemics of 1958 "Uma louca e maravilhosa jornada": epidemiologistas de campo do CDC nas epidemias de varíola e cólera do Paquistão Oriental em 1958

    Directory of Open Access Journals (Sweden)

    Paul Greenough

    2011-02-01

    Full Text Available In mid-April of 1958 the Government of Pakistan summoned the press to announce a grave need for international aid to cope with smallpox and cholera epidemics in East Pakistan. In response, and with the backing of the US State Department, Dr. Alexander D. Langmuir, chief epidemiologist of the CDC, led a team of epidemiologists to assist authorities in Dacca strengthen their immunization programs. Langmuir's superiors hoped for a Cold War advantage, but he saw an opportunity for trainees in the Epidemic Intelligence Service to learn about public health in a developing country. Langmuir later described the episode as a "wild and wondrous ride," but it had been more like a nightmare: the East Pakistan health department had collapsed; a popular movement had taken over vaccination and squandered vaccine supplies; hostile journalists had questioned the Americans' deeper motives; and a professional rivalry opened between the Americans and a British epidemiologist named Aidan Cockburn. By the time the epidemic subsided in July 1958, 30 million Bengalis had been vaccinated for smallpox but another 20,000 had succumbed to the disease. This episode was CDC's first sustained foreign intervention, a precursor to its extensive role in the 1970s helping WHO eradicate smallpox from Bangladesh.Em meados de abril de 1958, o Governo do Paquistão convocou a imprensa para anunciar a urgente necessidade de auxílio internacional para lidar com epidemias de varíola e cólera no Paquistão Oriental. Em resposta, e com o apoio do Departamento de Estado dos Estados Unidos, Dr. Alexander D. Langmuir, chefe de epidemiologia do CDC em Atlanta, liderou um time de epidemiologistas para auxiliar as autoridades em Dacca a reforçar seus programas de imunização. Os superiores de Langmuir ansiavam por demonstrações de capacidade dos EUA na Guerra Fria, mas ele vislumbrou uma chance para o Serviço de Inteligência Epidemiológica aprender sobre saúde pública em países em

  12. HPV Vaccine Awareness, Barriers, Intentions, and Uptake in Latina Women.

    Science.gov (United States)

    Lechuga, Julia; Vera-Cala, Lina; Martinez-Donate, Ana

    2016-02-01

    Latina women are at heightened risk of cervical cancer incidence and mortality. The human papillomavirus (HPV) is the principal cause of the majority of cervical cancer cases. A vaccine that protects against HPV was licensed in 2006. Eight years post-licensure, mixed research findings exist regarding the factors that predict vaccine uptake in Latinas. We conducted a population-based phone survey with a random sample of 296 Latinas living in a Midwestern U.S. City. Intention to vaccinate was significantly associated with health care provider recommendations, worry about side effects, knowing other parents have vaccinated, perceived severity of HPV, and worry that daughter may become sexually active following vaccination. Worry that daughter may become sexually active was the only factor related to vaccine uptake. Findings suggest that training providers to discuss the low risk of severe side effects, consequences of persistent HPV, and sexuality related concerns with Latino women may encourage vaccination.

  13. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Xin Wu

    2015-11-01

    Full Text Available Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD in humans and non-human primates (NHPs. Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs, vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirus∆VP30, recombinant cytomegalovirus (CMV-based vaccines, recombinant rabies virus (RABV-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

  14. Interwoven support: an historical survey of US federal programs enabling immunization.

    Science.gov (United States)

    Dalrymple, Dack W; Grabenstein, John D

    2014-11-28

    The US Government (USG) can date its involvement with immunization to military and civilian efforts in 1777 and 1813 to prevent smallpox. USG involvement began accelerating with federal licensing of vaccine and antibody manufacturers in 1903. In addition to ongoing regulation of manufacturing and product quality, military and civilian arms of the USG have led research efforts into new or improved vaccines. These efforts have included diseases endemic in the United States, as well as medical countermeasures targeted against biological weapons, influenza pandemics, and emerging infectious diseases. Especially since the 1950s, the USG has provided increasing levels of funding to purchase vaccines and conduct vaccination programs. These programs have focused largely on children, although vaccination programs for adults have been expanded somewhat in recent years. Multiple agencies of the USG have convened various panels of accomplished external experts who have generated widely regarded recommendations on vaccine safety and efficacy and optimal immunization practices. USG programs for safety assessment, injury compensation, liability protection, and disease surveillance have been developed to assess needs, evaluate safety questions, ensure vaccine supply, and foster confidence in vaccination efforts. Debates on the extent of government involvement date back to the 1890 s and continue today. Several pivotal expansions of government involvement followed disease outbreaks or manufacturing accidents. This historical survey describes each of the major US federal programs in these categories, including references to applicable law. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Ebola virus vaccines: an overview of current approaches

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Heinz

    2016-01-01

    Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. PMID:24575870

  16. Storytelling in the context of vaccine refusal: a strategy to improve communication and immunisation.

    Science.gov (United States)

    Cawkwell, Philip B; Oshinsky, David

    2016-03-01

    The December 2014 outbreak of measles in California impacted over 100 children and served as a reminder that this disease still plagues the USA, even 50 years following the first licensed vaccine. Refusal of vaccination is a complicated and multifaceted issue, one that clearly demands a closer look by paediatricians and public health officials alike. While medical doctors and scientists are trained to practice 'evidence-based medicine', and studies of vaccine safety and efficacy speak the language of statistics, there is reason to believe that this is not the most effective strategy for communicating with all groups of parents. Herein, we consider other methods such as narrative practices that employ stories and appeal more directly to parents. We also examine how doctors are trained to disseminate information and whether there are reasonable supplementary methods that could be used to improve vaccine communication and ultimately immunisation rates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. An Overview of Quadrivalent Human Papillomavirus Vaccine Safety

    DEFF Research Database (Denmark)

    Vichnin, Michelle; Bonanni, Paolo; Klein, Nicola P

    2015-01-01

    BACKGROUND: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6...

  18. Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria.

    Science.gov (United States)

    Hoffman, Stephen L; Billingsley, Peter F; James, Eric; Richman, Adam; Loyevsky, Mark; Li, Tao; Chakravarty, Sumana; Gunasekera, Anusha; Chattopadhyay, Rana; Li, Minglin; Stafford, Richard; Ahumada, Adriana; Epstein, Judith E; Sedegah, Martha; Reyes, Sharina; Richie, Thomas L; Lyke, Kirsten E; Edelman, Robert; Laurens, Matthew B; Plowe, Christopher V; Sim, B Kim Lee

    2010-01-01

    Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.

  19. Rotavirus Vaccines: a story of success with challenges ahead [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Miguel O’Ryan

    2017-08-01

    Full Text Available Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries.

  20. Adaptive Immunity to Francisella tularensis and Considerations for Vaccine Development

    Directory of Open Access Journals (Sweden)

    Lydia M. Roberts

    2018-04-01

    Full Text Available Francisella tularensis is an intracellular bacterium that causes the disease tularemia. There are several subspecies of F. tularensis whose ability to cause disease varies in humans. The most virulent subspecies, tularensis, is a Tier One Select Agent and a potential bioweapon. Although considerable effort has made to generate efficacious tularemia vaccines, to date none have been licensed for use in the United States. Despite the lack of a tularemia vaccine, we have learned a great deal about the adaptive immune response the underlies protective immunity. Herein, we detail the animal models commonly used to study tularemia and their recapitulation of human disease, the field's current understanding of vaccine-mediated protection, and discuss the challenges associated with new vaccine development.

  1. Eurogin Roadmap 2015: How has HPV knowledge changed our practice: Vaccines.

    Science.gov (United States)

    Brotherton, Julia M L; Jit, Mark; Gravitt, Patti E; Brisson, Marc; Kreimer, Aimée R; Pai, Sara I; Fakhry, Carole; Monsonego, Joseph; Franceschi, Silvia

    2016-08-01

    This review is one of two complementary reviews that have been prepared in the framework of the Eurogin Roadmap 2015 to evaluate how knowledge about HPV is changing practices in HPV infection and disease control through vaccination and screening. In this review of HPV vaccine knowledge, we present the most significant findings of the past year which have contributed to our knowledge of the two HPV prophylactic vaccines currently in widespread use and about the recently licensed nonavalent HPV vaccine. Whereas anal cancer is dealt with in the companion mini-review on screening, we also review here the rapidly evolving evidence regarding HPV-associated head and neck cancer and priority research areas. © 2016 UICC.

  2. BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination.

    Science.gov (United States)

    Chen, Fan; Yan, Qinying; Yu, Yang; Wu, Mei X

    2017-06-10

    Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The First Smallpox Epidemic on the Canadian Plains: In the Fur-traders' Words

    Directory of Open Access Journals (Sweden)

    C Stuart Houston

    2000-01-01

    Full Text Available William Tomison, in charge of the Hudson's Bay Company's Cumberland House on the Saskatchewan River, described the devastating smallpox epidemic of 1781 and 1782. He understood contagion, practised isolation and disinfection, and provided mortality statistics during a 'virgin soil' epidemic. Above all, he showed remarkable compassion. He and his men took dying Indians into their already crowded quarters, and provided them with food, shelter and 24 h care. This article describes the epidemic and its aftermath.

  4. Classical swine fever vaccines-State-of-the-art.

    Science.gov (United States)

    Blome, Sandra; Moß, Claudia; Reimann, Ilona; König, Patricia; Beer, Martin

    2017-07-01

    Due to its impact on animal health and pig industry, classical swine fever (CSF) is still one of the most important viral diseases of pigs. To control the disease, safe and highly efficacious live attenuated vaccines exist for decades. These vaccines have usually outstanding efficacy and safety but lack differentiability of infected from vaccinated animals (DIVA or marker strategy). In contrast, the first generation of E2 subunit marker vaccines shows constraints in efficacy, application, and production. To overcome these limitations, new generations of marker vaccines are developed. A wide range of approaches have been tried including recombinant vaccines, recombinant inactivated vaccines or subunit vaccines, vector vaccines, and DNA/RNA vaccines. During the last years, especially attenuated deletion vaccines or chimeric constructs have shown potential. At present, especially two new constructs have been intensively tested, the adenovirus-delivered, Semliki Forest virus replicon-vectored marker vaccine candidate "rAdV-SFV-E2" and the pestivirus chimera "CP7_E2alf". The later was recently licensed by the European Medicines Agency. Under field conditions, all marker vaccines have to be accompanied by a potent test system. Particularly this point shows still weaknesses and it is important to embed vaccination in a well-established vaccination strategy and a suitable diagnostic workflow. In summary, conventional vaccines are a standard in terms of efficacy. However, only vaccines with DIVA will allow improved eradication strategies e.g. also under emergency vaccination conditions in free regions. To answer this demand, new generations of marker vaccines have been developed and add now to the tool box of CSF control. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. [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.

  6. Estrategias, actores, promesas y temores en las campañas de vacunación antivariolosa en México: del Porfiriato a la Posrevolución (1880-1940 Strategies, actors, promises and fears in the smallpox vaccinations campaigns in Mexico: from the Porfiriato to the Post-revolution (1880-1940

    Directory of Open Access Journals (Sweden)

    Claudia Agostoni

    2011-02-01

    Full Text Available El artículo estudia algunas de las estrategias a las que recurrieron las autoridades de salud durante la puesta en marcha de programas vacunación antivariolosa durante los años de 1880 a 1940, periodo que corresponde al gobierno encabezado por Porfirio Díaz (1877-1911, a la fase armada de la Revolución Mexicana (1910-1920, y a las dos primeras décadas del estado posrevolucionario (1920-1940. Por una parte se prestará atención a la preeminencia que tuvo la vacunación en los centros urbanos, notablemente en la ciudad de México; y por la otra, se destacará la gradual, pero decisiva, organización y reglamentación de la vacunación antivariolosa en los programas destinados para el heterogéneo y desigual ámbito rural. Asimismo, se analizará la importancia que adquirió la educación higiénica, y se prestará atención a las divergentes respuestas que la aplicación masiva y cotidiana de la vacuna suscitó en las ciudades principales y en pequeños pueblos y municipios rurales, respuestas que incluyeron la resistencia, el temor, la incredulidad y la franca aceptación.The article examines some of the strategies employed by the Mexican health authorities that led to the organization of massive and obligatory smallpox vaccination campaigns from the late 1880s to the 1940s, a period of Mexican history that corresponds to the Porfirio Díaz regime (1877-1911, to the armed phase of the Mexican Revolution (1910-1920, and to the first two decades of the Post-revolutionary governments (1920-1940. Attention will be placed of the vaccination programs in the main urban settings, notably in Mexico City, as well as the gradual but decisive organization and regulation of vaccination campaigns in the heterogeneous rural milieu. Furthermore, the importance that hygienic education acquired will be explored, as well as the divergent and contested responses that emerged due to the obligatory vaccination campaigns, responses that included resistance, fear

  7. Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial

    Directory of Open Access Journals (Sweden)

    Beran Jiri

    2009-04-01

    Full Text Available Abstract Background Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine. Methods In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study. Results In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route. Conclusion

  8. Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial.

    Science.gov (United States)

    Gillet, Yves; Habermehl, Pirmin; Thomas, Stéphane; Eymin, Cécile; Fiquet, Anne

    2009-04-14

    When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) compared with the subcutaneous route. An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to 18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374) or subcutaneously (SC group, n = 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit. Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of >or= 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (vaccines was comparable regardless of administration route. Integration of both administration routes in the current European indications for the two vaccines will now allow physicians in Europe to choose their preferred administration route

  9. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review.

    Science.gov (United States)

    Elizaga, Marnie L; Vasan, Sandhya; Marovich, Mary A; Sato, Alicia H; Lawrence, Dale N; Chaitman, Bernard R; Frey, Sharon E; Keefer, Michael C

    2013-01-01

    Vaccinia-associated myo/pericarditis was observed during the US smallpox vaccination (DryVax) campaign initiated in 2002. A highly-attenuated vaccinia strain, modified vaccinia Ankara (MVA) has been evaluated in clinical trials as a safer alternative to DryVax and as a vector for recombinant vaccines. Due to the lack of prospectively collected cardiac safety data, the US Food and Drug Administration required cardiac screening and surveillance in all clinical trials of MVA since 2004. Here, we report cardiac safety surveillance from 6 phase I trials of MVA vaccines. Four clinical research organizations contributed cardiac safety data using common surveillance methods in trials administering MVA or recombinant MVA vaccines to healthy participants. 'Routine cardiac investigations' (ECGs and cardiac enzymes obtained 2 weeks after injections of MVA or MVA-HIV recombinants, or placebo-controls), and 'Symptom-driven cardiac investigations' are reported. The outcome measure is the number of participants who met the CDC-case definition for vaccinia-related myo/pericarditis or who experienced cardiac adverse events from an MVA vaccine. Four hundred twenty-five study participants had post-vaccination safety data analyzed, 382 received at least one MVA-containing vaccine and 43 received placebo; 717 routine ECGs and 930 cardiac troponin assays were performed. Forty-five MVA recipients (12%) had additional cardiac testing performed; 22 for cardiac symptoms, 19 for ECG/laboratory changes, and 4 for cardiac symptoms with an ECG/laboratory change. No participant had evidence of symptomatic or asymptomatic myo/pericarditis meeting the CDC-case definition and judged to be related to an MVA vaccine. Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants. ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603 NCT00301184 NCT00428337.

  10. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review.

    Directory of Open Access Journals (Sweden)

    Marnie L Elizaga

    Full Text Available Vaccinia-associated myo/pericarditis was observed during the US smallpox vaccination (DryVax campaign initiated in 2002. A highly-attenuated vaccinia strain, modified vaccinia Ankara (MVA has been evaluated in clinical trials as a safer alternative to DryVax and as a vector for recombinant vaccines. Due to the lack of prospectively collected cardiac safety data, the US Food and Drug Administration required cardiac screening and surveillance in all clinical trials of MVA since 2004. Here, we report cardiac safety surveillance from 6 phase I trials of MVA vaccines.Four clinical research organizations contributed cardiac safety data using common surveillance methods in trials administering MVA or recombinant MVA vaccines to healthy participants. 'Routine cardiac investigations' (ECGs and cardiac enzymes obtained 2 weeks after injections of MVA or MVA-HIV recombinants, or placebo-controls, and 'Symptom-driven cardiac investigations' are reported. The outcome measure is the number of participants who met the CDC-case definition for vaccinia-related myo/pericarditis or who experienced cardiac adverse events from an MVA vaccine.Four hundred twenty-five study participants had post-vaccination safety data analyzed, 382 received at least one MVA-containing vaccine and 43 received placebo; 717 routine ECGs and 930 cardiac troponin assays were performed. Forty-five MVA recipients (12% had additional cardiac testing performed; 22 for cardiac symptoms, 19 for ECG/laboratory changes, and 4 for cardiac symptoms with an ECG/laboratory change. No participant had evidence of symptomatic or asymptomatic myo/pericarditis meeting the CDC-case definition and judged to be related to an MVA vaccine.Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants.ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603 NCT00301184 NCT00428337.

  11. The Protestant medical missions to China: the introduction of Western medicine with vaccination.

    Science.gov (United States)

    Fu, Louis

    2013-05-01

    Modern medicine in China began with the arrival of Anglo-American Protestant missionaries in the early 19th century. Conditions were vastly different from the times of the Jesuits in Peking during the 17th and 18th centuries, when the priests enjoyed the endorsement of the Court and high officials. Faced with hostile and xenophobic officialdom and populace, surgeons of the British East India Company in collaboration with missionaries took the initiative. In 1805 Dr Alexander Pearson (1780-1874) introduced smallpox vaccination in Macao and Canton. Reverend Dr Robert Morrison (1782-1834) of the London Missionary Society with another East India Company Surgeon, Dr John Livingstone (1829) opened a dispensary for the poor in Macao in 1820. These pioneers paved the way for later Anglo-American medical missionaries who revolutionized medical practice in China.

  12. Overcoming barriers in HPV vaccination and screening programs

    Directory of Open Access Journals (Sweden)

    Alex Vorsters

    2017-12-01

    Full Text Available The Human Papillomavirus Prevention and Control Board brought together experts to discuss optimizing HPV vaccination and screening programs.Board members reviewed the safety profile of licensed HPV vaccines based on clinical and post-marketing data, reaching a consensus that current safety data is reassuring.Successful vaccination programs used well-coordinated communication campaigns, integrating (social media to spread awareness. Communication of evidence supporting vaccine effectiveness had beneficial effects on the perception of the vaccine. However, anti-vaccination campaigns have threatened existing programs in many countries.Measurement and monitoring of HPV vaccine confidence over time could help understand the nature and scale of waning confidence, define issues and intervene appropriately using context-specific evidence-based strategies. Finally, a broad group of stakeholders, such as teachers, health care providers and the media should also be provided with accurate information and training to help support prevention efforts through enhanced understanding of the risks and benefits of vaccination.Similarly, while cervical cancer screening through population-based programs is highly effective, barriers to screening exist: awareness in countries with population-based screening programs, access for vulnerable populations, and access and affordability in low- and middle-income countries. Integration of primary and secondary prevention has the potential to accelerate the decrease in cervical cancer incidence. Keywords: (max 6 Human papillomavirus, Vaccine, Screening, Barriers, Vaccine confidence

  13. Fulltext PDF

    Indian Academy of Sciences (India)

    They also knew that vaccines could boost the ability of the body to fight infections, since some infections, such as smallpox, were already being controlled with the help of vaccines. Infectious diseases were. [then as now] the bane of the developing world, and vaccines seemed [then as now] the ideal solutions for the future.

  14. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    Science.gov (United States)

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. © 2015 The Author(s) Published by S. Karger AG, Basel.

  15. Advanced Vaccine Candidates for Lassa Fever

    Directory of Open Access Journals (Sweden)

    Igor S. Lukashevich

    2012-10-01

    Full Text Available Lassa virus (LASV is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF. LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

  16. Cost-effectiveness of infant pneumococcal vaccination in the Netherlands

    NARCIS (Netherlands)

    Vemer, P.; Postma, M.J.

    2013-01-01

    Objectives: The Dutch National Immunization Program offers the 10-valent pneumococcal conjugate vaccine (PCV10). Also licensed for use in the infant population is the 13-valent PCV (PCV13). To update cost-effectiveness (CE) estimates of PCV13 over PCV10, using current epidemiological and economic

  17. Real-Time PCR Assay To Detect Smallpox Virus

    Science.gov (United States)

    Sofi Ibrahim, M.; Kulesh, David A.; Saleh, Sharron S.; Damon, Inger K.; Esposito, Joseph J.; Schmaljohn, Alan L.; Jahrling, Peter B.

    2003-01-01

    We developed a highly sensitive and specific assay for the rapid detection of smallpox virus DNA on both the Smart Cycler and LightCycler platforms. The assay is based on TaqMan chemistry with the orthopoxvirus hemagglutinin gene used as the target sequence. With genomic DNA purified from variola virus Bangladesh 1975, the limit of detection was estimated to be approximately 25 copies on both machines. The assay was evaluated in a blinded study with 322 coded samples that included genomic DNA from 48 different isolates of variola virus; 25 different strains and isolates of camelpox, cowpox, ectromelia, gerbilpox, herpes, monkeypox, myxoma, rabbitpox, raccoonpox, skunkpox, vaccinia, and varicella-zoster viruses; and two rickettsial species at concentrations mostly ranging from 100 fg/μl to 1 ng/μl. Contained within those 322 samples were variola virus DNA, obtained from purified viral preparations, at concentrations of 1 fg/μl to 1 ng/μl. On the Smart Cycler platform, 2 samples with false-positive results were detected among the 116 samples not containing variola virus tested; i.e., the overall specificity of the assay was 98.3%. On the LightCycler platform, five samples with false-positive results were detected (overall specificity, 95.7%). Of the 206 samples that contained variola virus DNA ranging in concentrations from 100 fg/μl to 1 ng/μl, 8 samples were considered negative on the Smart Cycler platform and 1 sample was considered negative on the LightCycler platform. Thus, the clinical sensitivities were 96.1% for the Smart Cycler instrument and 99.5% for the LightCycler instrument. The vast majority of these samples were derived from virus-infected cell cultures and variola virus-infected tissues; thus, the DNA material contained both viral DNA and cellular DNA. Of the 43 samples that contained purified variola virus DNA ranging in concentration from 1 fg/μl to 1 ng/μl, the assay correctly detected the virus in all 43 samples on both the Smart Cycler

  18. The clinical development process for a novel preventive vaccine: An overview

    Directory of Open Access Journals (Sweden)

    K Singh

    2016-01-01

    Full Text Available Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO, the European Medicines Agency (EMA, and the United States Food and Drug Administration (USFDA. The manuscript describes the objectives, study populations, study designs, study site, and outcome(s of each phase (Phase I-III of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.

  19. Preclinical evaluation of a Haemophilus influenzae type b conjugate vaccine process intended for technology transfer.

    Science.gov (United States)

    Hamidi, Ahd; Verdijk, Pauline; Kreeftenberg, Hans

    2014-01-01

    Introduction of Haemophilus influenzae type b (Hib) vaccine in low- and middle-income countries has been limited by cost and availability of Hib conjugate vaccines for a long time. It was previously recognized by the Institute for Translational Vaccinology (Intravacc, originating from the former Vaccinology Unit of the National Institute of Public Health [RIVM] and the Netherlands Vaccine Institute [NVI]) that local production of a Hib conjugate vaccine would increase the affordability and sustainability of the vaccine and thereby help to speed up Hib introduction in these countries. A new affordable and a non-infringing production process for a Hib conjugate vaccine was developed, including relevant quality control tests, and the technology was transferred to a number of vaccine manufacturers in India, Indonesia, and China. As part of the Hib technology transfer project managed by Intravacc, a preclinical toxicity study was conducted in the Netherlands to test the safety and immunogenicity of this new Hib conjugate vaccine. The data generated by this study were used by the technology transfer partners to accelerate the clinical development of the new Hib conjugate vaccine. A repeated dose toxicity and local tolerance study in rats was performed to assess the reactogenicity and immunogenicity of a new Hib conjugate vaccine compared to a licensed vaccine. The results showed that the vaccine was well tolerated and immunogenic in rats, no major differences in both safety and immunogenicity in rats were found between the vaccine produced according to the production process developed by Intravacc and the licensed one. Rats may be useful to verify the immunogenicity of Hib conjugate vaccines and for preclinical evaluation. In general, nonclinical evaluation of the new Hib conjugate vaccine, including this proof of concept (safety and immunogenicity study in rats), made it possible for technology transfer partners, having implemented the original process with no changes

  20. A Study of Waste Management within the COL Florence A. Blanchfield Army Community Hospital, Fort Campbell, Kentucky.

    Science.gov (United States)

    1981-08-01

    besnoiti Borna disease virus Bovine infectious petechial fever virus Camel pox virus Ephemeral fever virus Fowl plague virus Goat pox virus Hog...Varicella virus Vole rickettsia Yellow fever virus, 17D vaccine strain 69 Class 3 Alastrun, smallpox, monkeypox, and whitepox, when used in vitro Arbovirus...animal inoculation experiments Vesicular stomatitis virus Yellow fever virus - wild when used in vitro Class 4 Alastrun, smallpox, monkeypox, and

  1. New Kids on the Block: RNA-Based Influenza Virus Vaccines.

    Science.gov (United States)

    Scorza, Francesco Berlanda; Pardi, Norbert

    2018-04-01

    RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

  2. Update on the current status of cytomegalovirus vaccines.

    Science.gov (United States)

    Sung, Heungsup; Schleiss, Mark R

    2010-11-01

    Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design.

  3. Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

    Science.gov (United States)

    Angel, Juana; Steele, A Duncan; Franco, Manuel A

    2014-01-01

    Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

  4. Vaccines based on the cell surface carbohydrates of pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Jones Christopher

    2005-01-01

    Full Text Available Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development. This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

  5. Mathematical modeling provides kinetic details of the human immune response to vaccination

    Directory of Open Access Journals (Sweden)

    Dustin eLe

    2015-01-01

    Full Text Available With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combine mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response is determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increases slowly, the slow increase can still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model describes well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization are derived from the population of circulating antibody-secreting cells. Taken together, our analysis provides novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlight challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  6. Mathematical modeling provides kinetic details of the human immune response to vaccination.

    Science.gov (United States)

    Le, Dustin; Miller, Joseph D; Ganusov, Vitaly V

    2014-01-01

    With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response was determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increased slowly, the slow increase could still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model described well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization were derived from the population of circulating antibody-secreting cells. Taken together, our analysis provided novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlighted challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  7. The role of natural killer T cells in dendritic cell licensing, cross-priming and memory CD8+ T cell generation

    Directory of Open Access Journals (Sweden)

    Catherine eGottschalk

    2015-07-01

    Full Text Available New vaccination strategies focus on achieving CD8+ T cell (CTL immunity rather than on induction of protective antibody responses. While the requirement of CD4+ T (Th cell help in dendritic cell (DC activation and licensing, and in CTL memory induction has been described in several disease models, CTL responses may occur in a Th cell help independent manner. Natural Killer T cells (NKT cells can substitute for Th cell help and license DC as well. NKT cells produce a broad spectrum of Th1 and Th2 cytokines, thereby inducing a similar set of costimulatory molecules and cytokines in DC. This form of licensing differs from Th cell help by inducing other chemokines: while Th cell licensed DC produce CCR5 ligands, NKT cell-licensed DC produce CCL17 which attracts CCR4+ CD8+ T cells for subsequent activation. It has recently been shown that iNKT cells do not only enhance immune responses against bacterial pathogens or parasites, but also play a role in viral infections. The inclusion of NKT cell ligands in Influenza virus vaccines enhanced memory CTL generation and protective immunity in a mouse model. This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation.

  8. Malaria Vaccine Development: The Need for Novel Approach-es: A Review Article

    Directory of Open Access Journals (Sweden)

    Shima MAHMOUDI

    2018-03-01

    Full Text Available Background: Although rigorous efforts have substantially decreased the malaria burden through decades, it still threatens the lives of millions of children. Development of an effective vaccine can provide important approach in malaria control strategies. Unfortunately, development of an effective vaccine for falciparum malaria has been hindered by the extreme complexity of malaria parasite biology, complex and diverse parasite genomes, and immune evasion by the parasites as well as the intricate nature of the parasites infection cycle. The aim of this review was to discuss the different approaches to malaria vaccine development until now.Methods: Scientific databases, including MEDLINE (via PubMed and SCOPUS were searched up to 30 Jan 2017 and the articles regarding malaria vaccine development were taken into examination.Results: Several strategies for malaria vaccine development including pre-erythrocytic vaccines, antibody-based subunit vaccines, vectored vaccines, whole sporozoite vaccines, genetically Attenuated parasites and sporozoite subunit vaccine, erythrocytic vaccines, sexual stage vaccine, transmission-blocking vaccine as well as synthetic peptides and conjugate vaccine has been introduced. However, the success has been limited thus far.Conclusion: Although development of malaria vaccine over the past 70 year has been continued, the discovery, development, and licensing of a malaria vaccine formulation, which meets safety, affordability, accessibility, applicability, and efficacy has not yet been achieved.

  9. Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality From Diarrhea.

    Science.gov (United States)

    Burnett, Eleanor; Jonesteller, Christine L; Tate, Jacqueline E; Yen, Catherine; Parashar, Umesh D

    2017-06-01

    In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus vaccination on hospitalizations and deaths from rotavirus and all-cause acute gastroenteritis (AGE) during the first 10 years since vaccine licensure, including recent evidence from countries with high child mortality. We used standardized guidelines (PRISMA) to identify observational evaluations of rotavirus vaccine impact among children rotavirus AGE were reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low, medium, and high child mortality, respectively. Implementation of rotavirus vaccines has substantially decreased hospitalizations from rotavirus and all-cause AGE. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. A novel DNA vaccine technology conveying protection against a lethal herpes simplex viral challenge in mice.

    Directory of Open Access Journals (Sweden)

    Julie L Dutton

    Full Text Available While there are a number of licensed veterinary DNA vaccines, to date, none have been licensed for use in humans. Here, we demonstrate that a novel technology designed to enhance the immunogenicity of DNA vaccines protects against lethal herpes simplex virus 2 (HSV-2 challenge in a murine model. Polynucleotides were modified by use of a codon optimization algorithm designed to enhance immune responses, and the addition of an ubiquitin-encoding sequence to target the antigen to the proteasome for processing and to enhance cytotoxic T cell responses. We show that a mixture of these codon-optimized ubiquitinated and non-ubiquitinated constructs encoding the same viral envelope protein, glycoprotein D, induced both B and T cell responses, and could protect against lethal viral challenge and reduce ganglionic latency. The optimized vaccines, subcloned into a vector suitable for use in humans, also provided a high level of protection against the establishment of ganglionic latency, an important correlate of HSV reactivation and candidate endpoint for vaccines to proceed to clinical trials.

  11. Nanoengineering of vaccines using natural polysaccharides.

    Science.gov (United States)

    Cordeiro, Ana Sara; Alonso, María José; de la Fuente, María

    2015-11-01

    Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Outstanding challenges for rotavirus vaccine introduction in low-income countries

    DEFF Research Database (Denmark)

    Ustrup, Marte; Madsen, Lizell B; Bygbjerg, Ib C

    2011-01-01

    Rotavirus infections are the most common cause of severe diarrhoea in children worldwide. Two internationally licensed rotavirus vaccines have proven to be efficacious in middle and high-income countries and they could potentially be valuable tools for the prevention of rotavirus....... There is also a need for political commitment to prevent rotavirus infections as well as a need for an overall strengthening of the health systems in low-income countries. If these challenges were met, rotavirus vaccination could substantially improve child health and survival from rotavirus...

  13. Varicella and herpes zoster vaccine development: lessons learned.

    Science.gov (United States)

    Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith

    2017-12-01

    Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines' efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.

  14. Collaborative vaccine development: partnering pays.

    Science.gov (United States)

    Ramachandra, Rangappa

    2008-01-01

    Vaccine development, supported by infusions of public and private venture capital, is re-entering a golden age as one of the fastest growing sectors in the life-sciences industry. Demand is driven by great unmet need in underdeveloped countries, increased resistance to current treatments, bioterrorism, and for prevention indications in travelers, pediatric, and adult diseases. Production systems are becoming less reliant on processes such as egg-based manufacturing, while new processes can help to optimize vaccines. Expeditious development hinges on efficient study conduct, which is greatly enhanced through research partnerships with specialized contract research organizations (CROs) that are licensed and knowledgeable in the intricacies of immunology and with the technologic and scientific foundation to support changing timelines and strategies inherent to vaccine development. The CRO often brings a more objective assessment for probability of success and may offer alternative development pathways. Vaccine developers are afforded more flexibility and are free to focus on innovation and internal core competencies. Functions readily outsourced to a competent partner include animal model development, safety and efficacy studies, immunotoxicity and immunogenicity, dose response studies, and stability and potency testing. These functions capitalize on the CRO partner's regulatory and scientific talent and expertise, and reduce infrastructure expenses for the vaccine developer. Successful partnerships result in development efficiencies, elimination or reduced redundancies, and improved time to market. Keys to success include honest communications, transparency, and flexibility.

  15. Bacillus Calmette-Guérin Vaccination Using a Microneedle Patch

    Science.gov (United States)

    Hiraishi, Yasuhiro; Nandakumar, Subhadra; Choi, Seong-O; Lee, Jeong Woo; Kim, Yeu-Chun; Posey, James E.; Sable, Suraj B.; Prausnitz, Mark R.

    2011-01-01

    Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be a leading cause of mortality among bacterial diseases, and the bacillus Calmette-Guerin (BCG) is the only licensed vaccine for human use against this disease. TB prevention and control would benefit from an improved method of BCG vaccination that simplifies logistics and eliminates dangers posed by hypodermic needles without compromising immunogenicity. Here, we report the design and engineering of a BCG-coated microneedle vaccine patch for a simple and improved intradermal delivery of the vaccine. The microneedle vaccine patch induced a robust cell-mediated immune response in both the lungs and spleen of guinea pigs. The response was comparable to the traditional hypodermic needle based intradermal BCG vaccination and was characterized by a strong antigen specific lymphocyte proliferation and IFN-γ levels with high frequencies of CD4+IFN-γ+, CD4+TNF-α+ and CD4+IFN-γ+TNF-α+ T cells. The BCG-coated microneedle vaccine patch was highly immunogenic in guinea pigs and supports further exploration of this new technology as a simpler, safer, and compliant vaccination that could facilitate increased coverage, especially in developing countries that lack adequate healthcare infrastructure. PMID:21277407

  16. APPROACHING THE TARGET: THE PATH TOWARDS AN EFFECTIVE MALARIA VACCINE

    Directory of Open Access Journals (Sweden)

    Alberto L. García-Basteiro

    2012-01-01

    Full Text Available Eliciting an effective malaria vaccine has been the goal of the scientific community for many years. A malaria vaccine, added to existing tools and strategies, would further prevent and decrease the unacceptable malaria morbidity and mortality burden. Great progress has been made over the last decade, with some vaccine candidates in the clinical phases of development. The RTS,S malaria vaccine candidate, based on a recombinant P. falciparum protein, is the most advanced of such candidates, currently undergoing a large phase III trial. RTS,S has consistently shown an efficacy of around 50% against the first clinical episode of malaria, with protection in some cases extending up to 4 years of duration. Thus, it is hoped that this candidate vaccine will eventually become the first licensed malaria vaccine. This first vaccine against a human parasite is a groundbreaking achievement, but improved malaria vaccines conferring higher protection will be needed if the aspiration of malaria eradication is to be achieved

  17. Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Pauli, Gabrielle; Larsen, Tina H; Rak, Sabina

    2008-01-01

    BACKGROUND: Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. METHODS: A multicenter, randomi......-treated group. CONCLUSION: The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.......BACKGROUND: Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. METHODS: A multicenter......, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients...

  18. Dengue vaccines: Challenges, development, current status and prospects

    Directory of Open Access Journals (Sweden)

    A Ghosh

    2015-01-01

    Full Text Available Infection with dengue virus (DENV is the most rapidly spreading mosquito-borne viral disease in the world. The clinical spectrum of dengue, caused by any of the four serotypes of DENV, ranges from mild self-limiting dengue fever to severe dengue, in the form dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. Increased rates of hospitalization due to severe dengue, during outbreaks, result in massive economic losses and strained health services. In the absence of specific antiviral therapy, control of transmission of DENV by vector management is the sole method available for decreasing dengue-associated morbidity. Since vector control strategies alone have not been able to satisfactorily achieve reduction in viral transmission, the implementation of a safe, efficacious and cost-effective dengue vaccine as a supplementary measure is a high public health priority. However, the unique and complex immunopathology of dengue has complicated vaccine development. Dengue vaccines have also been challenged by critical issues like lack of animal models for the disease and absence of suitable markers of protective immunity. Although no licensed dengue vaccine is yet available, several vaccine candidates are under phases of development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored vaccines. Although some vaccine candidates have progressed from animal trials to phase II and III in humans, a number of issues regarding implementation of dengue vaccine in countries like India still need to be addressed. Despite the current limitations, collaborative effects of regulatory bodies like World Health Organization with vaccine manufacturers and policy makers, to facilitate vaccine development and standardize field trials can make a safe and efficacious dengue vaccine a reality in near future.

  19. Genome sequence diversity and clues to the evolution of variola (smallpox) virus.

    Science.gov (United States)

    Esposito, Joseph J; Sammons, Scott A; Frace, A Michael; Osborne, John D; Olsen-Rasmussen, Melissa; Zhang, Ming; Govil, Dhwani; Damon, Inger K; Kline, Richard; Laker, Miriam; Li, Yu; Smith, Geoffrey L; Meyer, Hermann; Leduc, James W; Wohlhueter, Robert M

    2006-08-11

    Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.

  20. The World Health Organization and global smallpox eradication.

    Science.gov (United States)

    Bhattacharya, S

    2008-10-01

    This article examines the multifaceted structures and complex operations of the World Health Organization and its regional offices; it also reassesses the form and the workings of the global smallpox eradication programme with which these bodies were closely linked in the 1960s and 1970s. Using the case study of South Asia, it seeks to highlight the importance of writing nuanced histories of international health campaigns through an assessment of differences between official rhetoric and practice. The article argues that the detailed examination of the implementation of policy in a variety of localities, within and across national borders, allows us to recognise the importance of the agency of field managers and workers. This analytical approach also helps us acknowledge that communities were able to influence the shape and the timing of completion of public health campaigns in myriad ways. This, in turn, can provide useful pointers for the design and management of health programmes in the contemporary world.

  1. The Benefits and Risks of Pandemic Influenza Vaccines

    NARCIS (Netherlands)

    E.G. Wijnans (Leonoor)

    2015-01-01

    markdownabstractIn 2009 and 2010 the world experienced the first influenza pandemic of the 21st century. As the new influenza A(H1N1)pdm09 virus spread across the world, vaccines were being produced and licensed at an unprecedented scale and speed. In Europe, adjuvanted and non-adjuvanted H1N1pdm09

  2. Immune responses to commercial equine vaccines against equine herpesvirus-1, equine influenza virus, eastern equine encephalomyelitis, and tetanus.

    Science.gov (United States)

    Holmes, Mark A; Townsend, Hugh G G; Kohler, Andrea K; Hussey, Steve; Breathnach, Cormac; Barnett, Craig; Holland, Robert; Lunn, D P

    2006-05-15

    Horses are commonly vaccinated to protect against pathogens which are responsible for diseases which are endemic within the general horse population, such as equine influenza virus (EIV) and equine herpesvirus-1 (EHV-1), and against a variety of diseases which are less common but which lead to greater morbidity and mortality, such as eastern equine encephalomyelitis virus (EEE) and tetanus. This study consisted of two trials which investigated the antigenicity of commercially available vaccines licensed in the USA to protect against EIV, EHV-1 respiratory disease, EHV-1 abortion, EEE and tetanus in horses. Trial I was conducted to compare serological responses to vaccines produced by three manufacturers against EIV, EHV-1 (respiratory disease), EEE, and tetanus given as multivalent preparations or as multiple vaccine courses. Trial II compared vaccines from two manufacturers licensed to protect against EHV-1 abortion, and measured EHV-1-specific interferon-gamma (IFN-gamma) mRNA production in addition to serological evidence of antigenicity. In Trial I significant differences were found between the antigenicity of different commercial vaccines that should be considered in product selection. It was difficult to identify vaccines that generate significant immune responses to respiratory viruses. The most dramatic differences in vaccine performance occurred in the case of the tetanus antigen. In Trial II both vaccines generated significant antibody responses and showed evidence of EHV-1-specific IFN-gamma mRNA responses. Overall there were wide variations in vaccine response, and the vaccines with the best responses were not produced by a single manufacturer. Differences in vaccine performance may have resulted from differences in antigen load and adjuvant formulation.

  3. Questions regarding the safety and duration of immunity following live yellow fever vaccination.

    Science.gov (United States)

    Amanna, Ian J; Slifka, Mark K

    2016-12-01

    The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas covered: We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert commentary: Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered.

  4. Questions regarding the safety and duration of immunity following live yellow fever vaccination

    Science.gov (United States)

    Amanna, Ian J.; Slifka, Mark K.

    2016-01-01

    Introduction The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas Covered We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert Commentary Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered. PMID:27267203

  5. Ebola Virus Vaccines – reality or fiction?

    Science.gov (United States)

    Mire, Chad E.; Geisbert, Thomas W.; Feldmann, Heinz

    2016-01-01

    For 40 years ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates. In December 2013 an unprecedented Zaire ebolavirus epidemic began in West Africa. Although “patient zero” has finally been reached after 2 years, the virus is again causing disease in the region. Currently there are no licensed vaccines or therapeutic countermeasures against ebolaviruses; however, the epidemic in West Africa has focused attention on the potential vaccine platforms developed over the past 15 years. There has been remarkable progress using a variety of platforms including DNA, subunit, and several viral vector approaches, replicating and non-replicating, which have shown varying degrees of protective efficacy in the “gold-standard” nonhuman primate models for Ebolavirus infections. A number of these vaccine platforms have moved into clinical trials over the past year with the hope of finding an efficacious vaccine to prevent future outbreaks/epidemics of Ebola hemorrhagic fever on the scale of the West African epidemic. PMID:27078187

  6. Controversy and debate on dengue vaccine series-paper 1: review of a licensed dengue vaccine: inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs.

    Science.gov (United States)

    Dans, Antonio L; Dans, Leonila F; Lansang, Mary Ann D; Silvestre, Maria Asuncion A; Guyatt, Gordon H

    2018-03-01

    Severe life-threatening dengue fever usually occurs when a child is infected by dengue virus a second time. This is caused by a phenomenon called antibody-dependent enhancement (ADE). Since dengue vaccines can mimic a first infection in seronegative children (those with no previous infection), a natural infection later in life could lead to severe disease. The possibility that dengue vaccines can cause severe dengue through ADE has led to serious concern regarding the safety of mass vaccination programs. A published meta-analysis addressed this safety issue for a new vaccine against dengue fever-Dengvaxia. The trials in this meta-analysis have been used to campaign for mass vaccination programs in developing countries. We discuss the results of this paper and point out problems in the analyses. Reporting the findings in an Asian trial (CYD14), the authors show a sevenfold rise in one outcome-hospitalization for dengue fever in children <5 years old. However, they fail to point out two signals of harm for another outcome-hospitalization for severe dengue fever (as confirmed by an independent data monitoring committee): 1. In children younger than 9 years, the relative risk was 8.5 (95% confidence interval [CI]: 0.5, 146.8), and 2. In the overall study group, the relative risk was 5.5 (95% CI: 0.9, 33). The authors conduct a subgroup analysis to support claims that the vaccine is probably safe among children aged 9 years or more. This subgroup analysis has limited credibility because: (1) it was a post hoc analysis; (2) it was one of a large number of subgroup analyses; (3) the test of interaction was not reported, but was insignificant (P = 0.14); and (4) there is no biological basis for a threshold age of 9 years. The more likely explanation for the higher risk in younger children is ADE, that is, more frequent seronegativity, rather than age itself. The selective reporting and inappropriate subgroup claims mask the potential harm of dengue mass vaccination

  7. Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

    KAUST Repository

    Gao, Ge

    2013-09-01

    BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

  8. Vacinas contra varicela e vacina quádrupla viral Varicella vaccines and measles, mumps, rubella, and varicella vaccine

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2006-07-01

    vaccine protects 70 to 90% of immunized children against any form of varicella zoster infection, but the efficacy against severe forms is higher (95 to 98%. This is a well-tolerated vaccine that causes few reactions. Since the vaccine was licensed, there have been three confirmed cases of transmission of the vaccine virus by domestic contacts to previously healthy people, who went on to develop mild disease. Despite evidence that the protection offered by this vaccine can wane over a number of years, it is not yet possible to state that a second dose is warranted, bearing in mind exposure to wild virus. After universal vaccination the chances of natural stimulation should drop and it is very probable that booster doses will become necessary. A measles, mumps, rubella, and varicella vaccine has recently been licensed that combines vaccines for measles, mumps, rubella and varicella in a single product with high rates of seroconversion. CONCLUSIONS: The Brazilian Society of Pediatrics recommends the varicella vaccine for children from 1 year on. We hope that the measles, mumps, rubella, and varicella vaccine will soon be available in Brazil, since combined vaccines facilitate wider vaccination coverage.

  9. Prospects and perspectives for development of a vaccine against herpes simplex virus infections.

    Science.gov (United States)

    McAllister, Shane C; Schleiss, Mark R

    2014-11-01

    Herpes simplex viruses 1 and 2 are human pathogens that lead to significant morbidity and mortality in certain clinical settings. The development of effective antiviral medications, however, has had little discernible impact on the epidemiology of these pathogens, largely because the majority of infections are clinically silent. Decades of work have gone into various candidate HSV vaccines, but to date none has demonstrated sufficient efficacy to warrant licensure. This review examines developments in HSV immunology and vaccine development published since 2010, and assesses the prospects for improved immunization strategies that may result in an effective, licensed vaccine in the near future.

  10. How Are New Vaccines Prioritized in Low-Income Countries? A Case Study of Human Papilloma Virus Vaccine and Pneumococcal Conjugate Vaccine in Uganda.

    Science.gov (United States)

    Wallace, Lauren; Kapirir, Lydia

    2017-04-08

    To date, research on priority-setting for new vaccines has not adequately explored the influence of the global, national and sub-national levels of decision-making or contextual issues such as political pressure and stakeholder influence and power. Using Kapiriri and Martin's conceptual framework, this paper evaluates priority setting for new vaccines in Uganda at national and sub-national levels, and considers how global priorities can influence country priorities. This study focuses on 2 specific vaccines, the human papilloma virus (HPV) vaccine and the pneumococcal conjugate vaccine (PCV). This was a qualitative study that involved reviewing relevant Ugandan policy documents and media reports, as well as 54 key informant interviews at the global level and national and sub-national levels in Uganda. Kapiriri and Martin's conceptual framework was used to evaluate the prioritization process. Priority setting for PCV and HPV was conducted by the Ministry of Health (MoH), which is considered to be a legitimate institution. While respondents described the priority setting process for PCV process as transparent, participatory, and guided by explicit relevant criteria and evidence, the prioritization of HPV was thought to have been less transparent and less participatory. Respondents reported that neither process was based on an explicit priority setting framework nor did it involve adequate representation from the districts (program implementers) or publicity. The priority setting process for both PCV and HPV was negatively affected by the larger political and economic context, which contributed to weak institutional capacity as well as power imbalances between development assistance partners and the MoH. Priority setting in Uganda would be improved by strengthening institutional capacity and leadership and ensuring a transparent and participatory processes in which key stakeholders such as program implementers (the districts) and beneficiaries (the public) are

  11. Childhood Tuberculosis: Epidemiology, Diagnosis, Treatment, and Vaccination

    Directory of Open Access Journals (Sweden)

    Kuo-Sheng Tsai

    2013-10-01

    Full Text Available Despite the existence of a government-run tuberculosis (TB control program, the current nationwide burden of TB continues to be a public health problem in Taiwan. Intense current and previous efforts into diagnostic, therapeutic, and preventive interventions have focused on TB in adults, but childhood TB has been relatively neglected. Children are particularly vulnerable to severe disease and death following infection, and children with latent infections become reservoirs for future transmission following disease reactivation in adulthood, thus fueling future epidemics. Additional research, understanding, and prevention of childhood TB are urgently needed. This review assesses the epidemiology, diagnosis, treatment, and relevant principles of TB vaccine development and presents efficacy data for the currently licensed vaccines.

  12. Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option.

    Science.gov (United States)

    Cui, Shuhui; Tobe, Ruoyan Gai; Mo, Xiuting; Liu, Xiaoyan; Xu, Lingzhong; Li, Shixue

    2016-11-15

    Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR. An economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio (ICER) compared to status quo. In a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years. RotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

  13. Aspergillus vaccines: Hardly worth studying or worthy of hard study?

    Science.gov (United States)

    Levitz, Stuart M

    2017-01-01

    Vaccines rank among the greatest advances in the history of public health. Yet, despite the need, there are no licensed vaccines to protect humans against fungal diseases, including aspergillosis. In this focused review, some of the major scientific and logistical challenges to developing vaccines to protect at-risk individuals against aspergillosis are discussed. Approaches that have shown promise in animal models include vaccines that protect against multiple fungal genera and those that are specifically directed to Aspergillus Advances in proteomics and glycomics have facilitated identification of candidate antigens for use in subunit vaccines. Novel adjuvants and delivery systems are becoming available that can skew vaccine responses toward those associated with protection. Immunotherapy consisting of adoptive transfer of Aspergillus-specific T cells to allogeneic hematopoietic transplant recipients has advanced to human testing but is technically difficult and of unproven benefit. While progress has been impressive, much work still needs to be done if vaccines against aspergillosis are to become a reality. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Canine distemper of vaccine origin in European mink, Mustela lutreola--a case report.

    Science.gov (United States)

    Ek-Kommonen, C; Rudbäck, E; Anttila, M; Aho, M; Huovilainen, A

    2003-04-02

    Cases of canine distemper (CD) related to vaccination of exotic carnivores extend over three decades and have been described in at least nine different species. Our report describes a case of acute CD in a European mink, Mustela lutreola, vaccinated with live attenuated CD vaccine licensed for use in fur-farmed mink. The male mink died of an acute grey matter disease with an unusually long incubation period. A female vaccinated at the same time showed no obvious signs of illness. The diagnosis was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and by subsequent sequencing of the PCR products. The sequenced products of the virus isolated from the mink and of the vaccine batch showed 100% identity. This is the first report in which molecular methods were used to confirm that the disease was caused by the vaccine strain. Based on our findings, it is clearly evident that current CD vaccines cannot be safely used in exotic species.

  15. Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors

    Directory of Open Access Journals (Sweden)

    Ulrich Desselberger

    2017-12-01

    Full Text Available Rotaviruses are a major cause of acute gastroenteritis in infants and young children worldwide and in many other mammalian and avian host species. Since 2006, two live-attenuated rotavirus vaccines, Rotarix® and RotaTeq®, have been licensed in >100 countries and are applied as part of extended program of vaccination (EPI schemes of childhood vaccinations. Whereas the vaccines have been highly effective in high-income countries, they were shown to be considerably less potent in low- and middle-income countries. Rotavirus-associated disease was still the cause of death in >200,000 children of <5 years of age worldwide in 2013, and the mortality is concentrated in countries of sub-Saharan Africa and S.E. Asia. Various factors that have been identified or suggested as being involved in the differences of rotavirus vaccine effectiveness are reviewed here. Recognition of these factors will help to achieve gradual worldwide improvement of rotavirus vaccine effectiveness.

  16. Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

    Directory of Open Access Journals (Sweden)

    Yoshikazu Nakayama

    2015-03-01

    Full Text Available Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region.

  17. Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

    Directory of Open Access Journals (Sweden)

    Aruna Chandran

    2010-07-01

    Full Text Available Aruna Chandran1, Sean Fitzwater1, Anjie Zhen2, Mathuram Santosham11Department of International Health, Division of Health Systems, 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAAbstract: Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.Keywords: vaccination, mortality, rotavirus, gastroenteritis

  18. A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation From Immunogenicity

    Directory of Open Access Journals (Sweden)

    David J. Dowling

    2016-12-01

    Full Text Available Background. Group B Neisseria meningitidis, an endotoxin-producing gram-negative bacterium, causes the highest incidence of group B meningococcus (MenB disease in the first year of life. The Bexsero vaccine is indicated in Europe from 8 weeks of age. Endotoxin components of outer membrane vesicles (OMVs or soluble lipopolysaccharide (LPS represent a potential source of inflammation and residual reactogenicity. The purpose of this study was to compare novel candidate MenB vaccine formulations with licensed vaccines, including Bexsero, using age-specific in vitro culture systems.Methods. OMVs from wild type and inactivated lpxL1 gene mutant N. meningitidis strains were characterized in human neonatal and adult in vitro whole blood assays and dendritic cell arrays. OMVs were benchmarked against licensed vaccines, including Bexsero and whole cell pertussis formulations, with respect to Th-polarizing cytokine and PGE2 production, as well as cell surface activation markers (HLA-DR, CD86, CCR7. OMV immunogenicity was assessed in mice.Results. ΔlpxLI native OMVs demonstrated significantly less cytokine induction in human blood and DCs than Bexsero and most of the other pediatric vaccines (e.g., PedvaxHib, EasyFive, Bacillus Calmette–Guérin (BCG tested. Despite a much lower inflammatory profile in vitro than Bexsero, ΔlpxLI native OMVs still had moderate DC maturing ability and induced robust anti-N. meningitidis antibody responses after murine immunization.Conclusions. A meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile in vitro induces robust antigen-specific immunogenicity in vivo.

  19. Options for improving effectiveness of rotavirus vaccines in developing countries.

    Science.gov (United States)

    Tissera, Marion S; Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L; Lyras, Dena; Kirkwood, Carl D; Buttery, Jim P

    2017-04-03

    Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30-60% in developing countries, but have been proven life-saving. Bridging this "efficacy gap" offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings.

  20. Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine--induced immunity.

    Science.gov (United States)

    He, Yong; Manischewitz, Jody; Meseda, Clement A; Merchlinsky, Michael; Vassell, Russell A; Sirota, Lev; Berkower, Ira; Golding, Hana; Weiss, Carol D

    2007-10-01

    The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27.

  1. Regulatory pathways for vaccines for developing countries.

    Science.gov (United States)

    Milstien, Julie; Belgharbi, Lahouari

    2004-01-01

    Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world. PMID:15042235

  2. Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates

    OpenAIRE

    Bolton, Diane L.; Santra, Sampa; Swett, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Kozlowski, Pamela A.; Letvin, Norman; Roederer, Mario; Radošević, Katarina

    2012-01-01

    Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag...

  3. A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

    Science.gov (United States)

    Aquino, Amalia Guadalupe Becerra; Brito, Maricruz Gutiérrez; Doniz, Carlos E Aranza; Herrera, Juan Francisco Galán; Macias, Mercedes; Zambrano, Betzana; Plennevaux, Eric; Santos-Lima, Eduardo

    2012-10-05

    To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Vaccine development against Leishmania donovani

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    Amrita eDas

    2012-05-01

    Full Text Available Visceral leishmaniasis (VL caused by Leishmania donovani and Leishmania infantum/ chagasi represents the second most challenging infectious disease worldwide, affecting nearly 500,000 people and 60,000 deaths annually. Zoonotic VL (ZVL caused by L. infantum is re-emergent canid zoonoses which represents a complex epidemiological cycle in New world where domestic dogs serve as reservoir host responsible for potentially fatal human infection where dog culling is the only control measure for eliminating reservoir host. Lifelong immunity in human against reinfection has motivated several attempts in developing prophylactic vaccines against the disease but very few have progressed beyond experimental stage. Absence of any licensed vaccine along with high toxicity and increasing resistance to the current chemotherapeutic drugs has further complicated the situation in endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge about pathogenesis, immune response and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine targets, their developmental status and future prospects in a quest for rational vaccine development against VL. In addition, several challenges such as safety issues, a renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing effective vaccines

  5. Rotavirus vaccines: safety, efficacy and public health impact.

    Science.gov (United States)

    Gray, J

    2011-09-01

    Rotaviruses are the cause of acute gastroenteritis, and disease is widespread amongst infants and young children throughout the world. Also, rotavirus is associated with significant mortality in developing countries with more than 500 000 children dying each year as a result of the severe dehydration associated with rotavirus disease. Efforts have been ongoing for more than 30 years to develop a safe and effective rotavirus vaccine. Currently, two vaccines, RotaRix and RotaTeq, have been licensed for use in many countries throughout the world following comprehensive safety and efficiency trials. Monitoring their effectiveness after licensure has confirmed that their incorporation into early childhood vaccination schedules can significantly prevent severe rotavirus diarrhoea, which would have resulted in hospitalizations, emergency room visits or increased diarrhoea-related mortality. Although the efficacy of both vaccines is lower at approximately 40-59% in developing countries, their use could significantly reduce the mortality associated with rotavirus disease that is concentrated in these countries. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  6. Recommendations on vaccination for Asian small animal practitioners: a report of the WSAVA Vaccination Guidelines Group.

    Science.gov (United States)

    Day, M J; Karkare, U; Schultz, R D; Squires, R; Tsujimoto, H

    2015-02-01

    In 2012 and 2013, the World Small Animal Veterinary Association (WSAVA) Vaccination Guidelines Group (VGG) undertook fact-finding visits to several Asian countries, with a view to developing advice for small companion animal practitioners in Asia related to the administration of vaccines to dogs and cats. The VGG met with numerous first opinion practitioners, small animal association leaders, academic veterinarians, government regulators and industry representatives and gathered further information from a survey of almost 700 veterinarians in India, China, Japan and Thailand. Although there were substantial differences in the nature and magnitude of the challenges faced by veterinarians in each country, and also differences in the resources available to meet those challenges, overall, the VGG identified insufficient undergraduate and postgraduate training in small companion animal microbiology, immunology and vaccinology. In most of the countries, there has been little academic research into small animal infectious diseases. This, coupled with insufficient laboratory diagnostic support, has limited the growth of knowledge concerning the prevalence and circulating strains of key infectious agents in most of the countries visited. Asian practitioners continue to recognise clinical infections that are now considered uncommon or rare in western countries. In particular, canine rabies virus infection poses a continuing threat to animal and human health in this region. Both nationally manufactured and international dog and cat vaccines are variably available in the Asian countries, but the product ranges are small and dominated by multi-component vaccines with a licensed duration of immunity (DOI) of only 1 year, or no description of DOI. Asian practitioners are largely unaware of current global trends in small animal vaccinology or of the WSAVA vaccination guidelines. Consequently, most practitioners continue to deliver annual revaccination with both core and non

  7. Rabies Outbreaks and Vaccination in Domestic Camels and Cattle in Northwest China.

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    Ye Liu

    2016-09-01

    Full Text Available In contrast to many countries where rabies has been well controlled in humans and livestock, even in wildlife, rabies is still endemic in almost regions of China. In Northwest China, rabies transmitted by stray dogs and wild foxes has caused heavy economic losses to local herdsmen, as well as causing numbers of human cases. In this study, as part of an investigation of ways to prevent rabies epidemics in livestock, we report an analysis of domestic cattle and camel rabies cases in Ningxia Hui (NHAR and Inner Mongolia Autonomous Region (IMAR and the immune efficacy of canine inactivated rabies vaccines in these animals. We found that rabies viruses from these animals are closely related to dog-hosted China I and fox-associated China III lineages, respectively, indicating that the infections originated from two different sources (dogs and wild foxes. As well as the previously reported Arctic and Arctic-related China IV lineage in IMAR, at least three separate phylogenetic groups of rabies virus consistently exist and spread throughout Northwest China. Since there is no licensed oral vaccine for wild foxes and no inactivated vaccine for large livestock, local canine inactivated vaccine products were used for emergency immunization of beef and milk cattle and bactrian (two-humped camels in local farms. Compared with a single injection with one (low-efficacy or three doses (high-cost, a single injection of a double dose of canine vaccine provided low-price and convenience for local veterinarians while inducing levels of virus neutralizing antibodies indicative of protection against rabies for at least 1 year in the cattle and camels. However, licensed vaccines for wildlife and large domestic animals are still needed in China.

  8. Persistence of bactericidal antibodies following early infant vaccination with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose.

    Science.gov (United States)

    Snape, Matthew D; Saroey, Praveen; John, Tessa M; Robinson, Hannah; Kelly, Sarah; Gossger, Nicoletta; Yu, Ly-Mee; Wang, Huajun; Toneatto, Daniela; Dull, Peter M; Pollard, Andrew J

    2013-10-15

    The multicomponent serogroup B meningococcal (4CMenB) vaccine was recently licensed for use in Europe. There are currently no data on the persistence of bactericidal antibodies induced by use of this vaccine in infants. Our objective was to evaluate serogroup B-specific bactericidal antibodies in children aged 40-44 months previously vaccinated at 2, 4, 6 and 12 months of age. Participants given 4 doses of 4CMenB as infants received a fifth dose of the vaccine at 40-44 months of age. Age-matched participants who were MenB vaccine-naive received 4CMenB and formed the control group. We evaluated human complement serum bactericidal activity (hSBA) titres at baseline and 1 month after each dose of 4CMenB. Before a booster dose at enrolment, 41%-76% of 17 participants previously vaccinated with 4CMenB in infancy had hSBA titres of 4 or greater against 4 reference strains. Before vaccination in the control group (n = 40) these proportions were similar for strains 44/76-SL (63%) and M10713 (68%) but low for strains NZ98/254 (0%) and 5/99 (3%). A booster dose in the 4CMenB-primed participants generated greater increases in hSBA titres than in controls. As has been observed with other meningococcal vaccines, bactericidal antibodies waned after vaccination with 4CMenB administered according to an approved infant vaccination schedule of 2, 4, 6 and 12 months of age, but there was an anamnestic response to a booster dose at 40-44 months of age. If 4CMenB were introduced into routine vaccination schedules, assessment of the need for a booster dose would require data on the impact of these declining titres on vaccine effectiveness. ClinicalTrials.gov, no. NCT01027351.

  9. Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option

    Directory of Open Access Journals (Sweden)

    Shuhui Cui

    2016-11-01

    Full Text Available Abstract Background Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR. Methods An economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs gained and incremental cost-effectiveness ratio (ICER compared to status quo. Results In a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years. Conclusions RotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

  10. Genetic diversity of G1P[8] rotavirus VP7 and VP8* antigens in Finland over a 20-year period: No evidence for selection pressure by universal mass vaccination with RotaTeq® vaccine.

    Science.gov (United States)

    Hemming, Maria; Vesikari, Timo

    2013-10-01

    Two live-attenuated oral vaccines (Rotarix™ and Rotateq®) against rotavirus gastroenteritis were licensed in 2006 and have been introduced into National Immunization Programs (NIPs) of several countries. Large scale use of rotavirus vaccines might cause antigenic pressure on circulating rotavirus types or lead to selection of new rotaviruses thus decreasing vaccine efficacy. We examined the nucleotide and amino acid sequences of the surface proteins VP7 and VP4 (cleaved to VP8(*) and VP5(*)) of a total of 108 G1P[8] rotavirus strains collected over a 20-year period from 1992, including the years 2006-2009 when rotavirus vaccine (mainly Rotarix™) was available, and the years 2009-2012 after implementation of RotaTeq® vaccine into the NIP of Finland. In G1 VP7 no changes at amino acid level were observed. In VP8(*) periodical fluctuation of the sublineage over the study period was found with multiple changes both at nucleotide and amino acid levels. Most amino acid changes were in the dominant antigenic epitopes of VP8(*). A change in VP8(*) sublineage occurred between 2008 and 2009, with a temporal correlation to the use of Rotarix™ up to 30% coverage in the period. In contrast, no antigenic changes in the VP8(*) protein appeared to be correlated to the exclusive use of RotaTeq® vaccine after 2009. Nevertheless, long-term surveillance of antigenic changes in VP4 and also VP7 proteins in wild-type rotavirus strains is warranted in countries with large scale use of the currently licensed live oral rotavirus vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. The decision to receive influenza vaccination among nurses in North and South Dakota.

    Science.gov (United States)

    Johansen, Laurie Jo; Stenvig, Thomas; Wey, Howard

    2012-01-01

    We examined the relationships between factors (intention, habit, facilitating conditions, and social, cognitive, and affective factors) and nurses' decisions about influenza vaccinations to understand why some get vaccinated while others do not. In a descriptive correlational design, the Triandis model of interpersonal behavior was used to examine the decision of nurses to receive influenza vaccinations. Participants were a random sample (N=193) of registered nurses in North and South Dakota drawn from the respective state nursing licensing board lists. Instrument construction and mail survey procedures followed Dillman's tailored design method. The response rate exceeded 80%. The findings revealed significant, positive correlations among all model variables. Item analysis showed that false beliefs about influenza disease and vaccinations were prevalent and that there was a wide variation in employer support for nurses getting vaccinated. Educational and social marketing strategies may improve nurse's knowledge about influenza disease and vaccine and increase vaccine uptake. Employers should be encouraged to promote and improve influenza vaccine accessibility in the workplace. Additional study is needed to understand how best to strengthen the influence of intention and habit on the decision of nurses to receive influenza vaccinations. © 2011 Wiley Periodicals, Inc.

  12. Identification and characterization of avian retroviruses in chicken embryo-derived yellow fever vaccines: investigation of transmission to vaccine recipients.

    Science.gov (United States)

    Hussain, Althaf I; Johnson, Jeffrey A; Da Silva Freire, Marcos; Heneine, Walid

    2003-01-01

    All currently licensed yellow fever (YF) vaccines are propagated in chicken embryos. Recent studies of chick cell-derived measles and mumps vaccines show evidence of two types of retrovirus particles, the endogenous avian retrovirus (EAV) and the endogenous avian leukosis virus (ALV-E), which originate from the chicken embryonic fibroblast substrates. In this study, we investigated substrate-derived avian retrovirus contamination in YF vaccines currently produced by three manufacturers (YF-vax [Connaught Laboratories], Stamaril [Aventis], and YF-FIOCRUZ [FIOCRUZ-Bio-Manguinhos]). Testing for reverse transcriptase (RT) activity was not possible because of assay inhibition. However, Western blot analysis of virus pellets with anti-ALV RT antiserum detected three distinct RT proteins in all vaccines, indicating that more than one source is responsible for the RTs present in the vaccines. PCR analysis of both chicken substrate DNA and particle-associated RNA from the YF vaccines showed no evidence of the long terminal repeat sequences of exogenous ALV subgroups A to D in any of the vaccines. In contrast, both ALV-E and EAV particle-associated RNA were detected at equivalent titers in each vaccine by RT-PCR. Quantitative real-time RT-PCR revealed 61,600, 348,000, and 1,665,000 ALV-E RNA copies per dose of Stamaril, YF-FIOCRUZ, and YF-vax vaccines, respectively. ev locus-specific PCR testing of the vaccine-associated chicken substrate DNA was positive both for the nondefective ev-12 locus in two vaccines and for the defective ev-1 locus in all three vaccines. Both intact and ev-1 pol sequences were also identified in the particle-associated RNA. To investigate the risks of transmission, serum samples from 43 YF vaccine recipients were studied. None of the samples were seropositive by an ALV-E-based Western blot assay or had detectable EAV or ALV-E RNA sequences by RT-PCR. YF vaccines produced by the three manufacturers all have particles containing EAV genomes and

  13. Medical experimentation concerning chemical and biological weapons for mass destruction.

    Science.gov (United States)

    Deutsch, Erwin

    2003-04-01

    This article is the text of a speech originally presented at the Second World Conference on Medical Ethics at Gijon, Spain, on 2 October 2002 under the title "Medical Experimentation Concerning Chemical and Biological Weapons for Mass Destruction: Clinical Design for New Smallpox Vaccines: Ethical and Legal Aspects." Experimentation on vaccines such as smallpox is subject to the usual ethical rules such as the need for informed consent. However, the participants will not often be at risk of catching the disease but expose themselves by taking part in the experimentation. Professor Deutsch explores the implications of this, including the position of vulnerable groups such as children, those with mental handicaps, and those acting under orders such as the miliary, the policy and fire officers.

  14. Pan-Influenza A Protection by Prime-Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model.

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime-boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro , CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo . Heterologous combination of prime (H1)-boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a "truly" universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising results

  15. Pan-Influenza A Protection by Prime–Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime–boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro, CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo. Heterologous combination of prime (H1)–boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a “truly” universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising

  16. 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV.

    Science.gov (United States)

    Pitisuttithum, Punnee; Velicer, Christine; Luxembourg, Alain

    2015-01-01

    Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.

  17. Dengue vaccine: come let's fight the menace.

    Science.gov (United States)

    Chawla, Sumit; Sahoo, Soumya Swaroop; Singh, Inderjeet; Verma, Madhur; Gupta, Vikas; Kumari, Sneh

    2015-01-01

    Although dengue has a global distribution, the World Health Organization (WHO) South-East Asia region together with Western Pacific region bears nearly 75% of the current global disease burden. Globally, the societal burden has been estimated to be approximately 528 to 1300 disability-adjusted life years (DALY) per million to populations in endemic regions Dengue is believed to infect 50 to 100 million people worldwide a year with half a million life-threatening infections requiring hospitalization, resulting in approximately 12,500 to 25,000 deaths. Despite being known for decades and nearly half the world's population is at risk for infection with as many as 100 million cases occurring annually, the pitiable state is that we still have no antiviral drugs to treat it and no vaccines to prevent it. In recent years, however, the development of dengue vaccines has accelerated dramatically in tandem with the burgeoning dengue problem with a rejuvenated vigour. However, recent progress in molecular-based vaccine strategies, as well as a renewed commitment by the World Health Organization (WHO) to co-ordinate global efforts on vaccine development, finally provides hope that control of this serious disease may be at hand. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on 5 candidate vaccines. Trials in the most advanced stages are showing encouraging preliminary data, and the leading candidate could be licensed as early as 2015.

  18. Implementation of Rotavirus Surveillance and Vaccine Introduction - World Health Organization African Region, 2007-2016.

    Science.gov (United States)

    Mwenda, Jason M; Burke, Rachel M; Shaba, Keith; Mihigo, Richard; Tevi-Benissan, Mable Carole; Mumba, Mutale; Biey, Joseph Nsiari-Muzeyi; Cheikh, Dah; Poy MSc, Alain; Zawaira, Felicitas R; Aliabadi, Negar; Tate, Jacqueline E; Hyde, Terri; Cohen, Adam L; Parashar, Umesh D

    2017-11-03

    Rotavirus is a leading cause of severe pediatric diarrhea globally, estimated to have caused 120,000 deaths among children aged rotavirus vaccination for all infants worldwide (2). Two rotavirus vaccines are currently licensed globally: the monovalent Rotarix vaccine (RV1, GlaxoSmithKline; 2-dose series) and the pentavalent RotaTeq vaccine (RV5, Merck; 3-dose series). This report describes progress of rotavirus vaccine introduction (3), coverage (using estimates from WHO and the United Nations Children's Fund [UNICEF]) (4), and impact on pediatric diarrhea hospitalizations in the WHO African Region. By December 2016, 31 (66%) of 47 countries in the WHO African Region had introduced rotavirus vaccine, including 26 that introduced RV1 and five that introduced RV5. Among these countries, rotavirus vaccination coverage (completed series) was 77%, according to WHO/UNICEF population-weighted estimates. In 12 countries with surveillance data available before and after vaccine introduction, the proportion of pediatric diarrhea hospitalizations that were rotavirus-positive declined 33%, from 39% preintroduction to 26% following rotavirus vaccine introduction. These results support introduction of rotavirus vaccine in the remaining countries in the region and continuation of rotavirus surveillance to monitor impact.

  19. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorragic E. coli (EHEC) and Campylobacter jejuni

    Science.gov (United States)

    O’Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Carlos Salazar, Juan; Montero, David

    2015-01-01

    In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral®), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp. Numerous vaccine candidates in earlier stages of development are discussed. PMID:25715096

  20. Gel-eletroforese no diagnóstico da varíola Gel-electrophoresis in the smallpox diagnosis

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    Julio A. Mesquita

    1972-01-01

    Full Text Available O emprego de gel-eletroforese no diagnóstico da varíola, demonstrou ser ao menos trinta vezes (30X mais sensível que o teste de agar-gel, nas condições descritas (tabela I. Doze (12 espécimes, cujos testes convencionais de inoculação em ovos embrionados e de agar-gel resultaram positivos, foram testados em suas diluições originais congeladas por mais de um ano, sendo seis deles revelados por gel-eletroforese enquanto nenhum o foi por agar-gel (tabela II. Trinta e três (33 amostras isoladas no laboratório, foram testadas com material colhido de membrana cório-alantóica da primeira inoculação para o diagnóstico, conservado em glicerina 50%, resultando 15 positivas em gel-eletroforese e apenas 3 em agar-gel (tabela II. Os últimos 60 espécimes recebidos para diagnóstico, através a Campanha de Erradicação da Varíola, também resultaram negativos em gel-eletroforese, que não mostrou falsos-positivos nas condições descritas.The test of gel-electrophoresis applied to the pox virus group showed to be at least thirth times (30X more sensitive than agar-gel test on the described conditions (Table I. Twelve specimens, which were positives form Smallpox in the conventional tests of egg inoculation and agar-gel difusion test, have been screened in their original dilutions frozen for more than 1 year and six of them were still detectable by gel-eletrophoresis, while by agar-gel test any of them was positive (Table II. Thirty three Smallpox isolates have been tested with material from first egg inoculation (chorioallantoic membranes which have been stored in glycerin 50%, at - 15ºC. Fifteen of them were still positive by gel-electrophoresis and only 3 by agar-gel (Table II. The last 60 specimens received for diagnosis from Smallpox Erradication Campaign (CEV, were negatives by both tests. The gel-electrophoresis, did not show false-positives on described conditions.

  1. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    Directory of Open Access Journals (Sweden)

    Marit Kramski

    Full Text Available The intentional re-introduction of Variola virus (VARV, the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV and Monkeypox virus (MPXV cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus.A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50 (minimal monkey infectious dose 50% of 8.3x10(2 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  2. Safety of pandemic H1N1 vaccines in children and adolescents

    NARCIS (Netherlands)

    E.G. Wijnans (Leonoor); S. de Bie (Sandra); J.P. Dieleman (Jeanne); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2011-01-01

    textabstractDuring the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of

  3. ITER licensing

    International Nuclear Information System (INIS)

    Gordon, C.W.

    2005-01-01

    ITER was fortunate to have four countries interested in ITER siting to the point where licensing discussions were initiated. This experience uncovered the challenges of licensing a first of a kind, fusion machine under different licensing regimes and helped prepare the way for the site specific licensing process. These initial steps in licensing ITER have allowed for refining the safety case and provide confidence that the design and safety approach will be licensable. With site-specific licensing underway, the necessary regulatory submissions have been defined and are well on the way to being completed. Of course, there is still work to be done and details to be sorted out. However, the informal international discussions to bring both the proponent and regulatory authority up to a common level of understanding have laid the foundation for a licensing process that should proceed smoothly. This paper provides observations from the perspective of the International Team. (author)

  4. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Science.gov (United States)

    van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino

    2011-01-01

    Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.

  5. Oral vaccination against plague using Yersinia pseudotuberculosis.

    Science.gov (United States)

    Demeure, Christian E; Derbise, Anne; Carniel, Elisabeth

    2017-04-01

    Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

    Science.gov (United States)

    Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  7. Cost-effectiveness analysis of rotavirus vaccination in Argentina.

    Science.gov (United States)

    Urueña, Analía; Pippo, Tomás; Betelu, María Sol; Virgilio, Federico; Hernández, Laura; Giglio, Norberto; Gentile, Ángela; Diosque, Máximo; Vizzotti, Carla

    2015-05-07

    Rotavirus is a leading cause of severe diarrhea in children under 5. In Argentina, the most affected regions are the Northeast and Northwest, where hospitalizations and deaths are more frequent. This study estimated the cost-effectiveness of adding either of the two licensed rotavirus vaccines to the routine immunization schedule. The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (Version 2.0) was used to assess health benefits, costs savings, life-years gained (LYGs), DALYs averted, and cost/DALY averted of vaccinating 10 successive cohorts, from the health care system and societal perspectives. Two doses of monovalent (RV1) rotavirus vaccine and three doses of pentavalent (RV5) rotavirus vaccine were each compared to a scenario assuming no vaccination. The price/dose was US$ 7.50 and US$ 5.15 for RV1 and RV5, respectively. We ran both a national and sub-national analysis, discounting all costs and benefits 3% annually. Our base case results were compared to a range of alternative univariate and multivariate scenarios. The number of LYGs was 5962 and 6440 for RV1 and RV5, respectively. The cost/DALY averted when compared to no vaccination from the health care system and societal perspective was: US$ 3870 and US$ 1802 for RV1, and US$ 2414 and US$ 358 for RV5, respectively. Equivalent figures for the Northeast were US$ 1470 and US$ 636 for RV1, and US$ 913 and US$ 80 for RV5. Therefore, rotavirus vaccination was more cost-effective in the Northeast compared to the whole country; and, in the Northwest, health service's costs saved outweighed the cost of introducing the vaccine. Vaccination with either vaccine compared to no vaccination was highly cost-effective based on WHO guidelines and Argentina's 2011 per capita GDP of US$ 9090. Key variables influencing results were vaccine efficacy, annual loss of efficacy, relative coverage of deaths, vaccine price, and discount rate. Compared to no

  8. The Dangerous Decline in the United States Military’s Infectious Disease Vaccine Program

    Science.gov (United States)

    2010-02-17

    of the 27th Special Operations Medical Group, Cannon Air Force Base, New Mexico . He has supported numerous combat operations including Operations...Japanese encephalitis.22 In addition, development of licensed vaccines for yellow fever, mumps, measles, varicella and oral polio was supervised

  9. Vaccine for BK Polyomavirus-associated Infections in Transplant Recipients | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    NCI researches identified a BK polyomavirus (BKV) virulent strain that causes chronic urinary tract infections, and the development of vaccine and therapeutic methods that would block BKV pathogenesis. The NCI Laboratory of Cellular Oncology, seek parties to license or co-develop this technology.

  10. A recombinant live attenuated tetravalent vaccine for the prevention of dengue.

    Science.gov (United States)

    Guy, Bruno; Noriega, Fernando; Ochiai, R Leon; L'azou, Maïna; Delore, Valentine; Skipetrova, Anna; Verdier, François; Coudeville, Laurent; Savarino, Stephen; Jackson, Nicholas

    2017-07-01

    Dengue is an important and still growing public health problem associated with substantial morbidity, as well as significant social and economic impact. The present review describes the main features and development of the first dengue vaccine (CYD-TDV, Dengvaxia®), which has been licensed by several dengue-endemic countries in Asia and Latin America for use in populations above 9 years of age. Areas covered: The review focuses on the large clinical development of CYD-TDV, which includes in particular two pivotal phase III efficacy trials conducted in Asia and Latin America and supported vaccine licensure. Based on these clinical data, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended considering introduction of the vaccine in geographic settings (national or subnational) with high burden of disease. Long-term safety follow-up studies of the efficacy trials are currently ongoing, and post-licensure studies will evaluate the vaccine effectiveness and safety in 'real-life' following vaccine introduction. Expert commentary: During vaccine development, a number of complexities were tackled, innovation pursued, and risk managed. These aspects, as well as the potential impact of CYD-TDV on public health are also discussed.

  11. A history of fish vaccination: science-based disease prevention in aquaculture.

    Science.gov (United States)

    Gudding, Roar; Van Muiswinkel, Willem B

    2013-12-01

    Disease prevention and control are crucial in order to maintain a sustainable aquaculture, both economically and environmentally. Prophylactic measures based on stimulation of the immune system of the fish have been an effective measure for achieving this goal. Immunoprophylaxis has become an important part in the successful development of the fish-farming industry. The first vaccine for aquaculture, a vaccine for prevention of yersiniosis in salmonid fish, was licensed in USA in 1976. Since then the use of vaccines has expanded to new countries and new species simultaneous with the growth of the aquaculture industry. This paper gives an overview of the achievements in fish vaccinology with particular emphasis on immunoprophylaxis as a practical tool for a successful development of bioproduction of aquatic animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

    Science.gov (United States)

    Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  13. Optimal Use of Vaccines for Control of Influenza A Virus in Swine

    Directory of Open Access Journals (Sweden)

    Matthew R. Sandbulte

    2015-01-01

    Full Text Available Influenza A virus in swine (IAV-S is one of the most important infectious disease agents of swine in North America. In addition to the economic burden of IAV-S to the swine industry, the zoonotic potential of IAV-S sometimes leads to serious public health concerns. Adjuvanted, inactivated vaccines have been licensed in the United States for over 20 years, and there is also widespread usage of autogenous/custom IAV-S vaccines. Vaccination induces neutralizing antibodies and protection against infection with very similar strains. However, IAV-S strains are so diverse and prone to mutation that these vaccines often have disappointing efficacy in the field. This scientific review was developed to help veterinarians and others to identify the best available IAV-S vaccine for a particular infected herd. We describe key principles of IAV-S structure and replication, protective immunity, currently available vaccines, and vaccine technologies that show promise for the future. We discuss strategies to optimize the use of available IAV-S vaccines, based on information gathered from modern diagnostics and surveillance programs. Improvements in IAV-S immunization strategies, in both the short term and long term, will benefit swine health and productivity and potentially reduce risks to public health.

  14. Small(pox success? Erradicação da varíola: medida do sucesso?

    Directory of Open Access Journals (Sweden)

    Anne-Emanuelle Birn

    2011-02-01

    Full Text Available The 30th anniversary of the World Health Organization's (WHO official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.O 30º aniversário da certificação oficial da Organização Mundial da Saúde (OMS da erradicação da varíola foi marcado por uma série de eventos que saudaram a dramática história do triunfo tecnológico e organizacional contra este antigo flagelo. Todavia, as comemorações também servem como momentos para uma reflexão crítica. Este artigo questiona os aplausos excessivos para a erradicação da varíola como o único e absoluto sucesso na história da saúde pública. Examina como e por que a erradicação da varíola e a abordagem da atenção básica de saúde orientada para a justiça social (de acordo com a Declaração de Alma-Ata se tornaram paradigmas concorrentes. Sintetiza críticas sobre as deficiências da erradicação e busca desvelar alguns dos mitos que envolvem a campanha de erradicação global como uma prioridade e necessidade da saúde pública, e como uma vitória da

  15. Managing the effect of TRIPS on availability of priority vaccines.

    Science.gov (United States)

    Milstien, Julie; Kaddar, Miloud

    2006-05-01

    The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world.

  16. Update on Key Studies - The Millennium Cohort Study, The STAMPEDE Study, The Million Veteran Program, and The National Health Study for a New Generation of US Veterans

    Science.gov (United States)

    2015-01-01

    Deployment scientific; ethical ; and legal experts in the field of genetics and veteran representatives, and partners, including but not limited to veterans...Smith TC, et al. Anthrax vaccination in the Millennium Cohort: validation and measures of health. Am J Prev Med. 2007;32:347–353. 20. Smith B, Smith...LeardMann CA, Smith B, Smith TC, Wells TS, Ryan MAK. Smallpox vaccination : comparison of self-reported and electronic vaccine records in the millennium

  17. Genetic characterization of L-Zagreb mumps vaccine strain.

    Science.gov (United States)

    Ivancic, Jelena; Gulija, Tanja Kosutic; Forcic, Dubravko; Baricevic, Marijana; Jug, Renata; Mesko-Prejac, Majda; Mazuran, Renata

    2005-04-01

    Eleven mumps vaccine strains, all containing live attenuated virus, have been used throughout the world. Although L-Zagreb mumps vaccine has been licensed since 1972, only its partial nucleotide sequence was previously determined (accession numbers , and ). Therefore, we sequenced the entire genome of L-Zagreb vaccine strain (Institute of Immunology Inc., Zagreb, Croatia). In order to investigate the genetic stability of the vaccine, sequences of both L-Zagreb master seed and currently produced vaccine batch were determined and no difference between them was observed. A phylogenetic analysis based on SH gene sequence has shown that L-Zagreb strain does not belong to any of established mumps genotypes and that it is most similar to old, laboratory preserved European strains (1950s-1970s). L-Zagreb nucleotide and deduced protein sequences were compared with other mumps virus sequences obtained from the GenBank. Emphasis was put on functionally important protein regions and known antigenic epitopes. The extensive comparisons of nucleotide and deduced protein sequences between L-Zagreb vaccine strain and other previously determined mumps virus sequences have shown that while the functional regions of HN, V, and L proteins are well conserved among various mumps strains, there can be a substantial amino acid difference in antigenic epitopes of all proteins and in functional regions of F protein. No molecular pattern was identified that can be used as a distinction marker between virulent and attenuated strains.

  18. Cold-adapted live attenuated influenza vaccines developed in Russia: Can they contribute to meeting the needs for influenza control in other countries?

    International Nuclear Information System (INIS)

    Kendal, Alan P.

    1997-01-01

    It is now more than 30 years since the first cold-adapted influenza viruses were developed in Russia as potential live, attenuated vaccines. In the past 15-20 years considerable experience has been gained from Russian and joint Russian-US laboratory and clinical studies with type A monovalent and bivalent vaccines prepared with genetic reassortant viruses derived from one of these cold-adapted viruses in particular, A/Leningrad/134/57. More recent experiences include use of trivalent cold-adapted vaccines with a type B component. The overall high level of safety of individual and combined vaccines in pre-school and school-aged children, with illness reductions in open field trials equivalent to that seen with inactivated vaccines, is such as to suggest that practical measures might now be justified to facilitate expansion of the use of these vaccines to other countries. It is proposed that further experimentation with the Russian cold-adapted live attenuated vaccines should be focused on issues that will relate to the public health perspective, i.e. selection of the single best candidate type A and B vaccines for intense study using as criteria their potential for meeting licensing requirements outside Russia, and documenting the clinical protective efficacy of a single vaccine dose compared to two doses as studied until now. Resolution of these issues is important to ensure that costs for future live vaccine production, control, and utilization will be kept at lowest levels so that expanded use of live vaccines will have maximum cost-benefit and affordability. To guide those interested in these issues, examples are given of populations for whom a licensed live cold-adapted vaccine might be considered, together with indications of extra data needed to fully validate each suggested use

  19. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Directory of Open Access Journals (Sweden)

    Pierre van Damme

    Full Text Available Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine.All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907.

  20. Immunization. Safety and Use of Polio Vaccines. Briefing Report to the Chairman, Subcommittee on Natural Resources, Agriculture Research and Environment, Committee on Science, Space, and Technology, House of Representatives.

    Science.gov (United States)

    General Accounting Office, Washington, DC.

    This report presents information on the status of the safety and use of polio vaccines in the United States. Topics discussed include: (1) the role of the Food and Drug Administration (FDA) in processing an inactivated polio vaccine license application; (2) the steps the federal government has taken to improve the safety of the vaccine; (3) the…

  1. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Directory of Open Access Journals (Sweden)

    Irina Margine

    2014-10-01

    Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.

  2. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 3 - Vaccines.

    Science.gov (United States)

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    This study assessed research knowledge gaps in the field of FMDV (foot-and-mouth disease virus) vaccines. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD vaccine research. Vaccines play a vital role in FMD control, used both to limit the spread of the virus during epidemics in FMD-free countries and as the mainstay of disease management in endemic regions, particularly where sanitary controls are difficult to apply. Improvements in the performance or cost-effectiveness of FMD vaccines will allow more widespread and efficient disease control. FMD vaccines have changed little in recent decades, typically produced by inactivation of whole virus, the quantity and stability of the intact viral capsids in the final preparation being key for immunogenicity. However, these are exciting times and several promising novel FMD vaccine candidates have recently been developed. This includes the first FMD vaccine licensed for manufacture and use in the USA; this adenovirus-vectored FMD vaccine causes in vivo expression of viral capsids in vaccinated animals. Another promising vaccine candidate comprises stabilized empty FMDV capsids produced in vitro in a baculovirus expression system. Recombinant technologies are also being developed to improve otherwise conventionally produced inactivated vaccines, for example, by creating a chimeric vaccine virus to increase capsid stability and by inserting sequences into the vaccine virus for desired antigen expression. Other important areas of ongoing research include enhanced adjuvants, vaccine quality control procedures and predicting vaccine protection from immune correlates, thus reducing dependency on animal challenge studies. Globally, the degree of independent vaccine evaluation is highly variable, and this is essential for vaccine quality. Previously neglected, the

  3. Multifaceted contributions: health workers and smallpox eradication in India.

    Science.gov (United States)

    Bhattacharya, Sanjoy

    2008-01-01

    Smallpox eradication in South Asia was a result of the efforts of many grades of health-workers. Working from within the confines of international organisations and government structures, the role of the field officials, who were of various nationalities and also drawn from the cities and rural enclaves of the countries in these regions, was crucial to the development and deployment of policies. However, the role of these personnel is often downplayed in official histories and academic histories, which highlight instead the roles played by a handful of senior officials within the World Health Organization and the federal governments in the sub-continent. This article attempts to provide a more rounded assessment of the complex situation in the field. In this regard, an effort is made to underline the great usefulness of the operational flexibility displayed by field officers, wherein lessons learnt in the field were made an integral part of deploying local campaigns; careful engagement with the communities being targeted, as well as the employment of short term workers from amongst them, was an important feature of this work.

  4. Fulltext PDF

    Indian Academy of Sciences (India)

    Unknown

    items produced by the international media also tend to annoy me: most of them refer to the disease ... Smallpox Eradication Archives of the World Health Organization. ... governmental standpoints and, sometimes, oppose vaccination, and the ...

  5. Assessment of immunogenicity and safety following primary and booster immunisation with a CRM197 -conjugated Haemophilus influenzae type B vaccine in healthy Chinese infants.

    Science.gov (United States)

    Jun, L; Yuguo, C; Zhiguo, W; Jinfeng, L; Huawei, M; Xiuhua, L; Yonggui, Z; Yanhua, X; Kong, Y; Hongtao, L; Yuliang, Z

    2013-10-01

    Invasive meningitis and pneumonia caused by Haemophilus influenzae type b (Hib) is an important cause of childhood mortality in countries where Hib vaccination is not routine. We evaluated the non-inferiority of a licensed Hib vaccine, PRP-CRM(197) compared with a second licensed Hib vaccine, PRP-T, following the recommended Chinese immunisation schedule for infants between 6 months and 1 year of age. In the first study phase, 6-12 month-old infants received two primary doses of either PRP-CRM(197) (n = 335) or PRP-T (n = 335) vaccine administered 1 month apart. In the second study phase 8 months later, the same children received a single booster dose of vaccine identical to that use for priming (PRP-CRM(197), n = 327; PRP-T, n = 333). Serum levels of anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Non-inferiority of primary and booster doses was assessed in terms of percentages of subjects with anti-PRP antibody levels associated with providing short-term (≥ 0.15 μg/ml) and long-term (≥ 1.0 μg/ml) protection; the non-inferiority margin was set at -5%. PRP-CRM(197) was demonstrated to be non-inferior to PRP-T. Anti-PRP antibodies levels ≥ 0.15 μg/ml and ≥ 1.0 μg/ml were achieved by 97% of infants in the PRP-CRM(197) group and 98% of infants in the PRP-T group 1 month after primary immunisation, and by all subjects (100%) in both vaccine groups 1 month after booster administration. Safety profiles for both vaccines were similar; no serious adverse events, deaths or adverse events leading to withdrawal occurred during the study. PRP-CRM(197) was well-tolerated and immunologically non-inferior to a licensed comparator Hib vaccine in Chinese infants (Clinicaltrials.gov: NCT01044316 & NCT01226953). © 2013 John Wiley & Sons Ltd.

  6. Potency assay design for adjuvanted recombinant proteins as malaria vaccines.

    Science.gov (United States)

    Giersing, Birgitte K; Dubovsky, Filip; Saul, Allan; Denamur, Francoise; Minor, Philip; Meade, Bruce

    2006-05-15

    Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modern vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development.

  7. A turkey rhinotracheitis outbreak caused by the environmental spread of a vaccine-derived avian metapneumovirus.

    Science.gov (United States)

    Lupini, Caterina; Cecchinato, Mattia; Ricchizzi, Enrico; Naylor, Clive J; Catelli, Elena

    2011-10-01

    Avian metapneumovirus (aMPV) subtype A was isolated from 7-week-old turkeys showing respiratory disease typical of turkey rhinotracheitis. Comparison of the virus sequence with previously determined vaccine marker sequences showed that the virulent virus had originated from a licensed live subtype A aMPV vaccine. The vaccine had neither been in use on the farm within a period of at least 6 months nor had it been used on farms within a distance of approximately 5 km. Isolation of the virus and exposure to naive turkeys caused disease typical of a virulent aMPV field strain. The study shows that disease was caused by exposure to aMPV vaccine-derived virus that was present in the environment, and indicates that such virus is able to circulate for longer than was previously envisaged.

  8. Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships.

    Science.gov (United States)

    Olson, Victoria A; Karem, Kevin L; Smith, Scott K; Hughes, Christine M; Damon, Inger K

    2009-04-01

    Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.

  9. Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro® and a varicella vaccine (VARIVAX® by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Thomas Stéphane

    2009-04-01

    Full Text Available Abstract Background When this trial was initiated, the combined measles, mumps and rubella (MMR vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro® and a varicella vaccine (VARIVAX® compared with the subcutaneous route. Methods An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374 or subcutaneously (SC group, n = 378. Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit. Results Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of ≥ 1.25 gpELISA units/ml. Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (≤ 2.5 cm. There was a trend for lower rates of injection-site erythema and swelling in the IM group. The incidence and nature of systemic adverse events were comparable for the two routes

  10. Development of a multicomponent Staphylococcus aureus vaccine designed to counter multiple bacterial virulence factors

    Science.gov (United States)

    Anderson, Annaliesa S.; Miller, Alita A.; Donald, Robert G.K.; Scully, Ingrid L.; Nanra, Jasdeep S.; Cooper, David; Jansen, Kathrin U.

    2012-01-01

    Staphylococcus aureus is a major cause of healthcare-associated infections and is responsible for a substantial burden of disease in hospitalized patients. Despite increasingly rigorous infection control guidelines, the prevalence and corresponding negative impact of S. aureus infections remain considerable. Difficulties in controlling S. aureus infections as well as the associated treatment costs are exacerbated by increasing rates of resistance to available antibiotics. Despite ongoing efforts over the past 20 years, no licensed S. aureus vaccine is currently available. However, learnings from past clinical failures of vaccine candidates and a better understanding of the immunopathology of S. aureus colonization and infection have aided in the design of new vaccine candidates based on multiple important bacterial pathogenesis mechanisms. This review outlines important considerations in designing a vaccine for the prevention of S. aureus disease in healthcare settings. PMID:22922765

  11. A review of the literature on the economics of vaccination against TB.

    Science.gov (United States)

    Tu, Hong-Anh T; Vu, Hoa D; Rozenbaum, Mark H; Woerdenbag, Herman J; Postma, Maarten J

    2012-03-01

    The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in particular, miliary TB and tuberculous meningitis. However, it has a limited effect in preventing pulmonary TB, which occurs more frequently in adults. BCG vaccination has now been implemented in more than 157 countries worldwide. For various countries, the benefits of vaccination are only limited and potentially not cost effective. The International Union Against Tuberculosis and Lung Diseases had set the criteria for discontinuation of BCG vaccination in 1994. This decision, however, was not based on economic considerations. Many developed countries have met the criteria set by the International Union Against Tuberculosis and Lung Disease and stopped universal BCG vaccination. For developing countries, the BCG vaccine is still an effective intervention in protecting young children from TB infection. A lot of effort has been spent on R&D of new TB vaccines, the first of which are expected to be available within 5-7 years from now. Novel TB vaccines are expected to be better and more effective than the current BCG vaccine and should provide a viable strategy in controlling TB morbidity and mortality. In this review, the aim is to explore economic evaluations that have been carried out for vaccination against TB worldwide. In addition to epidemiological evidence, economic evidence can play a crucial role in supporting the governments of countries in making proper public health decisions on BCG vaccination policies, in particular, to implement, continue, or discontinue.

  12. The yellow fever 17D vaccine virus as a vector for the expression of foreign proteins: development of new live flavivirus vaccines

    Directory of Open Access Journals (Sweden)

    Myrna C Bonaldo

    2000-01-01

    Full Text Available The Flaviviridae is a family of about 70 mostly arthropod-borne viruses many of which are major public health problems with members being present in most continents. Among the most important are yellow fever (YF, dengue with its four serotypes and Japanese encephalitis virus. A live attenuated virus is used as a cost effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The rise of recombinant DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine development. One new approach is the use of cDNAs encopassing the whole viral genome to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of viral mutants with considerable potential as new live attenuated viruses. The use of infectious cDNA as a carrier for heterologous antigens is gaining importance as chimeric viruses are shown to be viable, immunogenic and less virulent as compared to the parental viruses. The use of DNA to overcome mutation rates intrinsic of RNA virus populations in conjunction with vaccine production in cell culture should improve the reliability and lower the cost for production of live attenuated vaccines. The YF virus despite a long period ignored by researchers probably due to the effectiveness of the vaccine has made a come back, both in nature as human populations grow and reach endemic areas as well as in the laboratory being a suitable model to understand the biology of flaviviruses in general and providing new alternatives for vaccine development through the use of the 17D vaccine strain.

  13. Advances and Future Challenges in Recombinant Adenoviral Vectored H5N1 Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2012-11-01

    Full Text Available The emergence of a highly pathogenic avian influenza virus H5N1 has increased the potential for a new pandemic to occur. This event highlights the necessity for developing a new generation of influenza vaccines to counteract influenza disease. These vaccines must be manufactured for mass immunization of humans in a timely manner. Poultry should be included in this policy, since persistent infected flocks are the major source of avian influenza for human infections. Recombinant adenoviral vectored H5N1 vaccines are an attractive alternative to the currently licensed influenza vaccines. This class of vaccines induces a broadly protective immunity against antigenically distinct H5N1, can be manufactured rapidly, and may allow mass immunization of human and poultry. Recombinant adenoviral vectors derived from both human and non-human adenoviruses are currently being investigated and appear promising both in nonclinical and clinical studies. This review will highlight the current status of various adenoviral vectored H5N1 vaccines and will outline novel approaches for the future.

  14. License renewal

    International Nuclear Information System (INIS)

    Newberry, S.

    1993-01-01

    This article gives an overview of the process of license renewal for nuclear power plants. It explains what is meant by license renewal, the significance of license renewal, and goes over key elements involved in the process of license renewal. Those key elements are NRC requirements embodied in 10 CFR Part 54 (Reactor Safety) and 10 CFR Part 51 (Environmental Issues). In addition Industry Reports must be developed and reviewed. License renewal is essentially the process of applying for a 20 year extension to the original 40 year operating license granted for the plant. This is a very long term process, which involves a lot of preparation, and compliance with regulatory rules and guidelines. In general it is a process which is expected to begin when plants reach an operating lifetime of 20 years. It has provisions for allowing the public to become involved in the review process

  15. Early Impact of Human Papillomavirus Vaccination on Cervical Neoplasia—Nationwide Follow-up of Young Danish Women

    DEFF Research Database (Denmark)

    Baldur-Felskov, Birgitte; Dehlendorff, Christian; Munk, Christian

    2014-01-01

    +) and of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) were statistically significantly reduced among vaccinated women in birth cohorts 1991 to 1994 (1991-1992atypia+: hazard ratio [HR] = 0.46, two-sided 95% confidence interval [CI] = 0.39 to 0.56; 1991-1992CIN2/3: HR = 0.56, 95% CI = 0.37 to 0.84; 1993......BACKGROUND: In clinical trials, vaccines against human papillomavirus (HPV) have been highly effective against HPV16- or HPV18-associated cervical lesions. The quadrivalent HPV vaccine was licensed in 2006 and subsequently implemented in the Danish vaccination program. The study aim was to use...... individual information on HPV vaccination status to assess subsequent risk of cervical lesions. METHODS: Using a cohort study design, we identified all girls and women born in Denmark in the period from 1989 to 1999 and obtained information on individual HPV vaccination status in the period from 2006 to 2012...

  16. Cost-effectiveness analysis of routine pneumococcal vaccination in the UK: a comparison of the PHiD-CV vaccine and the PCV-13 vaccine using a Markov model.

    Science.gov (United States)

    Delgleize, Emmanuelle; Leeuwenkamp, Oscar; Theodorou, Eleni; Van de Velde, Nicolas

    2016-11-30

    In 2010, the 13-valent pneumococcal conjugate vaccine (PCV-13) replaced the 7-valent vaccine (introduced in 2006) for vaccination against invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) in the UK. Using recent evidence on the impact of PCVs and epidemiological changes in the UK, we performed a cost-effectiveness analysis (CEA) to compare the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with PCV-13 in the ongoing national vaccination programme. CEA was based on a published Markov model. The base-case scenario accounted only for direct medical costs. Work days lost were considered in alternative scenarios. Calculations were based on serotype and disease-specific vaccine efficacies, serotype distributions and UK incidence rates and medical costs. Health benefits and costs related to IPD, pneumonia and AOM were accumulated over the lifetime of a UK birth cohort. Vaccination of infants at 2, 4 and 12 months with PHiD-CV or PCV-13, assuming complete coverage and adherence. The incremental cost-effectiveness ratio (ICER) was computed by dividing the difference in costs between the programmes by the difference in quality-adjusted life-years (QALY). Under our model assumptions, both vaccines had a similar impact on IPD and pneumonia, but PHiD-CV generated a greater reduction in AOM cases (161 918), AOM-related general practitioner consultations (31 070) and tympanostomy tube placements (2399). At price parity, PHiD-CV vaccination was dominant over PCV-13, saving 734 QALYs as well as £3.68 million to the National Health Service (NHS). At the lower list price of PHiD-CV, the cost-savings would increase to £45.77 million. This model projected that PHiD-CV would provide both incremental health benefits and cost-savings compared with PCV-13 at price parity. Using PHiD-CV could result in substantial budget savings to the NHS. These savings could be used to implement other life-saving interventions

  17. Cervical cancer and HPV: Awareness and vaccine acceptability among parents in Morocco.

    Science.gov (United States)

    Mouallif, Mustapha; Bowyer, Harriet L; Festali, Soukaina; Albert, Adelin; Filali-Zegzouti, Younes; Guenin, Samuel; Delvenne, Philippe; Waller, Jo; Ennaji, Moulay Mustapha

    2014-01-09

    Cervical cancer is a major public health concern in Morocco where it represents the second most common and lethal cancer in women. Human papillomavirus (HPV) vaccines have been licensed in Morocco since 2008 but there are no available data on their acceptability. This study aimed to assess awareness of HPV and the vaccine, and to identify factors associated with acceptability of the vaccine among parents in Morocco. We carried out a questionnaire-based survey using face-to-face interviews in a sample of 852 parents (670 mothers and 182 fathers) with at least one unmarried daughter ≤26 years. We collected data within public and private health centres and clinics in four regions in Morocco between July and August 2012. The main outcome measure was parental acceptability of the HPV vaccine for their daughter(s). Responses revealed very low awareness of HPV infection (4.7%) and the HPV vaccine (14.3%). None of the participants had vaccinated their daughter(s) against HPV and vaccine acceptability was low among mothers (32%) and fathers (45%). Higher education and income, previous awareness of the HPV vaccine and endorsement of the belief that a recommendation from the Ministry of Health or a doctor to have the vaccine would be encouraging, were associated with mothers' HPV vaccine acceptability. Non-acceptability among mothers was associated with having more than two daughters, believing the vaccine was expensive, lack of information and believing that whatever happens to an individual's health is God's will. The only factor associated with the fathers' acceptability of the vaccine was the cost of the vaccine. Increasing HPV and HPV vaccine awareness through educational campaigns, along with active recommendation by physicians and a publically funded vaccination programme could increase parental acceptability of the HPV vaccine in Morocco. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Protective Immunity against Tularemia Provided by an Adenovirus-Vectored Vaccine Expressing Tul4 of Francisella tularensis

    OpenAIRE

    Kaur, Ravinder; Chen, Shan; Arévalo, Maria T.; Xu, Qingfu; Chen, Yanping; Zeng, Mingtao

    2012-01-01

    Francisella tularensis, a category A bioterrorism agent, is a highly infectious organism that is passed on via skin contact and inhalation routes. A live attenuated vaccine strain (LVS) has been developed, but it has not been licensed for public use by the FDA due to safety concerns. Thus, there exists a need for a safer and improved vaccine. In this study, we have constructed a replication-incompetent adenovirus, Ad/opt-Tul4, carrying a codon-optimized gene for expression of a membrane prote...

  19. Diarrheal Diseases Hospitalization in Yemen before and after Rotavirus Vaccination

    Directory of Open Access Journals (Sweden)

    Mohammed Amood AL-Kamarany

    2016-01-01

    Full Text Available The study aims to assess the impact of rotavirus vaccine introduction on diarrheal diseases hospitalization and to identify the rotavirus genotypes most prevalent before and after vaccine introduction among children ≤ 5 years of age. Rotarix™ ® rotavirus vaccine is currently licensed for infants in Yemen and was introduced in 2012. The vaccination course consists of two doses. The first dose is administrated at 6 weeks of age and the second dose is completed by 10 weeks. Based on a longitudinal observational study, we assessed the impact of vaccination on rotavirus hospitalization before and after vaccination among children ≤ 5 years of age at the Yemeni-Swedish Hospital (YSH in Taiz, Yemen. Prevaccination covered January 2009–July 2012 during which 2335 fecal samples were collected from children ≤ 5 years old. Postvaccination covered January 2013–December 2014 during which 1114 fecal samples were collected. Rotavirus was detected by Enzyme Linkage Immunosorbent Assay (ELISA. The incidence of rotavirus hospitalization decreased from 43.79% in 2009 to 10.54% in 2014. Hospitalization due to rotavirus diarrhea was reduced by 75.93%. Vaccine coverage increased from 23% in 2012 to 72% in 2014. Also, the results showed that the most predominant genotypes in prevaccination period were G2P[4] (55.0%, followed by G1P[8] (15.0%, while in postvaccination period G1P[8] (31% was the predominant genotype, followed by G9P[8] (27.5%. In conclusion, rotavirus vaccination in Yemen resulted in sharp reduction in diarrheal hospitalization. A successful rotavirus vaccination program in Yemen will rely upon efficient vaccine delivery systems and sustained vaccine efficacy against diverse and evolving rotavirus strains.

  20. Cost-effectiveness analysis of vaccinating children in Malawi with RTS,S vaccines in comparison with long-lasting insecticide-treated nets.

    Science.gov (United States)

    Seo, Mikyung Kelly; Baker, Peter; Ngo, Karen Ngoc-Lan

    2014-02-24

    New RTS,S malaria vaccines may soon be licensed, yet its cost-effectiveness is unknown. Before the widespread introduction of RTS,S vaccines, cost-effectiveness studies are needed to help inform governments in resource-poor settings about how best to prioritize between the new vaccine and existing malaria interventions. A Markov model simulated malaria progression in a hypothetical Malawian birth cohort. Parameters were based on published data. Three strategies were compared: no intervention, vaccination at one year, and long-lasting, insecticide-treated nets (LLINs) at birth. Both health service and societal perspectives were explored. Health outcomes were measured in disability-adjusted life years (DALYs) averted and costed in 2012 US$. Incremental cost-effectiveness ratios (ICERs) were calculated and extensive sensitivity analyses were conducted. Three times GDP per capita ($1,095) per DALY averted was used for a cost-effectiveness threshold, whilst one times GDP ($365) was considered 'very cost-effective'. From a societal perspective the vaccine strategy was dominant. It averted 0.11 more DALYs than LLINs and 0.372 more DALYs than the no intervention strategy per person, while costing $10.04 less than LLINs and $59.74 less than no intervention. From a health service perspective the vaccine's ICER was $145.03 per DALY averted, and thus can be considered very cost-effective. The results were robust to changes in all variables except the vaccine and LLINs' duration of efficacy. Vaccines remained cost-effective even at the lowest assumed efficacy levels of 49.6% (mild malaria) and 14.2% (severe malaria), and the highest price of $15. However, from a societal perspective, if the vaccine duration efficacy was set below 2.69 years or the LLIN duration of efficacy was greater than 4.24 years then LLINs became the more cost-effective strategy. The results showed that vaccinating Malawian children with RTS,S vaccines was very cost-effective from both a societal and a

  1. Perceived Need for a Parental Decision Aid for the HPV Vaccine: Content and Format Preferences

    Science.gov (United States)

    Lechuga, Julia; Swain, Geoffrey; Weinhardt, Lance S.

    2014-01-01

    The human papillomavirus (HPV) is a precursor of cervical cancer. In 2006, the Federal Drug Administration licensed a vaccine to protect against four types of HPV. Three years postlicensure of the vaccine, HPV vaccination is still fraught with controversy. To date, research suggests that contrary to popular notions, parents are less concerned with controversies on moral issues and more with uncertainty regarding because long-term safety of a drug is resolved after licensure. This study was designed to understand whether mothers from diverse ethnicities perceive a need for a decision support tool. Results suggest that the design of a culturally tailored decision support tool may help guide parents through the decision-making process. PMID:21444922

  2. Perceived need of a parental decision aid for the HPV vaccine: content and format preferences.

    Science.gov (United States)

    Lechuga, Julia; Swain, Geoffrey; Weinhardt, Lance S

    2012-03-01

    The human papillomavirus (HPV) is a precursor of cervical cancer. In 2006, the Federal Drug Administration licensed a vaccine to protect against four types of HPV. Three years postlicensure of the vaccine, HPV vaccination is still fraught with controversy. To date, research suggests that contrary to popular notions, parents are less concerned with controversies on moral issues and more with uncertainty regarding because long-term safety of a drug is resolved after licensure. This study was designed to understand whether mothers from diverse ethnicities perceive a need for a decision support tool. Results suggest that the design of a culturally tailored decision support tool may help guide parents through the decision-making process.

  3. Transmission of vaccinia virus, possibly through sexual contact, to a woman at high risk for adverse complications.

    Science.gov (United States)

    Said, Maria A; Haile, Charles; Palabindala, Venkataraman; Barker, Naomi; Myers, Robert; Thompson, Ruth; Wilson, Lucy; Allan-Martinez, Frances; Montgomery, Jay; Monroe, Benjamin; Tack, Danielle; Reynolds, Mary; Damon, Inger; Blythe, David

    2013-12-01

    Severe adverse events, including eczema vaccinatum (EV), can result after smallpox vaccination. Persons at risk for EV include those with underlying dermatologic conditions, such as atopic dermatitis. We investigated a case of vaccinia infection, possibly acquired during sexual contact with a recently vaccinated military service member, in a female Maryland resident with atopic dermatitis. The U.S. Department of Defense's Vaccine Healthcare Centers Network (VHCN) and the Centers for Disease Control and Prevention (CDC) worked in conjunction with the patient's physician and the Maryland Department of Health and Mental Hygiene (DHMH) to confirm the diagnosis, ensure treatment, and prevent further transmission. Specimens collected from the patient were tested at the DHMH laboratories and were positive by real-time polymerase chain reaction for nonvariola orthopoxvirus. Testing at the CDC verified the presence of vaccinia-specific DNA signatures. Continuing spread of the patient's lesions led to the administration of vaccinia immune globulin and strict infection control measures to prevent tertiary transmission to vulnerable family members, also with atopic dermatitis. VHCN contacted the service member to reinforce vaccination site care and hygiene. This case underscores the importance of prevaccination education for those receiving the smallpox vaccine to protect contacts at risk for developing severe adverse reactions. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

  4. cost-benefit analysis of anti-retroviral therapy (art) for hiv/aids

    African Journals Online (AJOL)

    user

    HIV/AIDS is high and that is why most patients cannot access HIV/AIDS treatment even though these drugs are supposed to .... Laboratory in New Mexico, Dr. Gerald Myers, and ... tuberculosis, and vaccinations against smallpox represented ...

  5. Evaluation of live attenuated S79 mumps vaccine effectiveness in mumps outbreaks: a matched case-control study.

    Science.gov (United States)

    Fu, Chuan-xi; Nie, Jun; Liang, Jian-hua; Wang, Ming

    2009-02-05

    Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live attenuated S(79) mumps vaccine has been licensed for pediatric use since 1990. The objective of this study was to determine the effectiveness of live attenuated S(79) mumps vaccine against clinical mumps in outbreaks. Cases were selected from mumps outbreaks in schools in Guangzhou between 2004 and 2005. Each case was matched by gender, age and classroom. Vaccination information was obtained from Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for 1 or 2 doses of S(79) vaccine with 95% confidence intervals (CI). One hundred and ninety-four cases and 194 controls were enrolled into the study. VE of the S(79) mumps vaccine for 1 dose versus 0 confer protection 80.4% (95% CI, 60.0%-90.4%) and VEs against mumps in outbreaks for 1 dose of mumps vaccine are similar among those children aged 4-9 years and aged over 10 years old. The live attenuated S(79) mumps vaccine can be effective in preventing clinical mumps outbreaks.

  6. Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG®): a global review.

    Science.gov (United States)

    Maki, Joanne; Guiot, Anne-Laure; Aubert, Michel; Brochier, Bernard; Cliquet, Florence; Hanlon, Cathleen A; King, Roni; Oertli, Ernest H; Rupprecht, Charles E; Schumacher, Caroline; Slate, Dennis; Yakobson, Boris; Wohlers, Anne; Lankau, Emily W

    2017-09-22

    RABORAL V-RG ® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control

  7. Strategies for continuous evaluation of the benefit-risk profile of HPV-16/18-AS04-adjuvanted vaccine.

    Science.gov (United States)

    Angelo, Maria-Genalin; Taylor, Sylvia; Struyf, Frank; Tavares Da Silva, Fernanda; Arellano, Felix; David, Marie-Pierre; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

    2014-11-01

    The HPV types 16/18-AS04-adjuvanted cervical cancer vaccine, Cervarix(®) (HPV-16/18-vaccine, GlaxoSmithKline, Belgium) was first approved in 2007 and is licensed in 134 countries for the prevention of persistent infection, premalignant cervical lesions and cervical cancer caused by oncogenic HPV. Benefit-risk status requires continual re-evaluation as vaccine uptake increases, as the epidemiology of the disease evolves and as new information becomes available. This paper provides an example of benefit-risk considerations and risk-management planning. Evaluation of the benefit-risk of HPV-16/18-vaccine post-licensure includes studies with a range of designs in many countries and in collaboration with national public agencies and regulatory authorities. The strategy to assess benefit versus risk will continue to evolve and adapt to the changing HPV-16/18-vaccine market.

  8. Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

    Science.gov (United States)

    Mahoney, R T; Francis, D P; Frazatti-Gallina, N M; Precioso, A R; Raw, I; Watler, P; Whitehead, P; Whitehead, S S

    2012-07-06

    A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. Although this study does not seek to compute the price of the final

  9. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon

    Science.gov (United States)

    Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K.; Alcami, Antonio

    2010-01-01

    Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. PMID:20019241

  10. A purified inactivated Japanese encephalitis virus vaccine made in Vero cells.

    Science.gov (United States)

    Srivastava, A K; Putnak, J R; Lee, S H; Hong, S P; Moon, S B; Barvir, D A; Zhao, B; Olson, R A; Kim, S O; Yoo, W D; Towle, A C; Vaughn, D W; Innis, B L; Eckels, K H

    2001-08-14

    A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals. The manufacturing process was efficient in generating a high yield of virus, essentially free of contaminating host cell proteins and nucleic acids. The PIV was formulated with aluminum hydroxide and administered to mice by subcutaneous inoculation. Vaccinated animals developed high-titered JE virus neutralizing antibodies in a dose dependent fashion after two injections. The vaccine protected mice against morbidity and mortality after challenge with live, virulent, JE virus. Compared with the existing licensed mouse brain-derived vaccine, JE-Vax, the Vero cell-derived JE-PIV was more immunogenic and as effective as preventing encephalitis in mice. The JE-PIV is currently being tested for safety and immunogenicity in volunteers.

  11. Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain.

    Science.gov (United States)

    Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia

    2013-12-26

    The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFNγ-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Effectiveness of rotavirus vaccines against hospitalisations in Japan.

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    Fujii, Yoshiyuki; Noguchi, Atsuko; Miura, Shinobu; Ishii, Haruka; Nakagomi, Toyoko; Nakagomi, Osamu; Takahashi, Tsutomu

    2017-07-11

    In Japan, rotavirus hospitalisation occurs at a rate from 2.8 to 13.7 per 1000 child-years among children age less than 5 years, and it imposes a substantial burden to the healthcare system in the country. While both monovalent (RV1) and pentavalent (RV5) rotavirus vaccines are licensed in Japan, neither has been incorporated in the national infant immunization programme. In this study, we estimated vaccine effectiveness (VE) in Japan. This study was conducted in Yuri-Kumiai General Hospital located in a city in the north-western part of Japan. Age-eligible children for rotavirus vaccination were enrolled if they were hospitalized for rotavirus gastroenteritis between September 2013 and August 2016. Rotavirus gastroenteritis was defined by the detection of rotavirus antigen by immunochromatography. "Vaccinated" was defined as infant inoculated with at least one dose of either RV1 or RV5. A conditional logistic regression analysis was performed by modelling the year of birth, year of admission, residence of the children and vaccination status, and by matching the age of cases with that of test-negative controls. The adjusted odds ratio of the vaccinated over unvaccinated was then used to calculate VE in the formula of (1 - adjusted odds ratio) × 100. Out of the 244 patients enrolled, rotavirus antigen was detected in 55 (22.5%) of whom 10 (18.2%) were vaccinated, whereas 94 (49.7%) of 189 test-negative controls were vaccinated. During the study period, the vaccine uptake rate in the controls increased from 36.2% to 61.8%. On the other hand, the vaccination coverage over the three years was 64.2% in Yuri-Honjo city (three quarters of the catchment), and 91.4% in Nikaho city (one quarter of the catchment). The VE was calculated to be 70.4% (95% confidence interval: 36.0-86.4%, P = 0.002). The point estimate of the VE was lower but its 95% confidence interval overlaps those of the efficacies obtained from clinical trials in Japan. The rotavirus vaccine was

  13. [Comparison of protective properties of the smallpox DNA-vaccine based on the variola virus A30L gene and its variant with modified codon usage].

    Science.gov (United States)

    Maksiutov, R A; Shchelkunov, S N

    2011-01-01

    Efficacy of candidate DNA-vaccines based on the variola virus natural gene A30L and artificial gene A30Lopt with modified codon usage, optimized for expression in mammalian cells, was tested. The groups of mice were intracutaneously immunized three times with three-week intervals with candidate DNA-vaccines: pcDNA_A30L or pcDNA_A30Lopt, and in three weeks after the last immunization all mice in the groups were intraperitoneally infected by the ectromelia virus K1 strain in 10 LD50 dose for the estimation of protection. It was shown that the DNA-vaccines based on natural gene A30L and codon-optimized gene A30Lopt elicited virus, thereby neutralizing the antibody response and protected mice from lethal intraperitoneal challenge with the ectromelia virus with lack of statistically significant difference.

  14. Non-Human Primate Models of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    Anne Schmitt

    2014-06-01

    Full Text Available Smallpox, one of the most destructive diseases, has been successfully eradicated through a worldwide vaccination campaign. Since immunization programs have been stopped, the number of people with vaccinia virus induced immunity is declining. This leads to an increase in orthopoxvirus (OPXV infections in humans, as well as in animals. Additionally, potential abuse of Variola virus (VARV, the causative agent of smallpox, or monkeypox virus, as agents of bioterrorism, has renewed interest in development of antiviral therapeutics and of safer vaccines. Due to its high risk potential, research with VARV is restricted to two laboratories worldwide. Therefore, numerous animal models of other OPXV infections have been developed in the last decades. Non-human primates are especially suitable due to their close relationship to humans. This article provides a review about on non-human primate models of orthopoxvirus infections.

  15. Recent advances in canine leptospirosis: focus on vaccine development

    Directory of Open Access Journals (Sweden)

    Klaasen HLBM

    2015-06-01

    Full Text Available Henricus LBM (Eric Klaasen,1 Ben Adler2 1Global Companion Animals Research and Development, Merck Sharp and Dohme Animal Health, Boxmeer, the Netherlands; 2Department of Microbiology, Monash University, Clayton, VIC, Australia Abstract: Leptospirosis is a global infection of humans and animals caused by pathogenic Leptospira spp. Leptospirosis is a major zoonosis, with infection acquired from wild and domestic animals. It is also a significant cause of morbidity, mortality, and economic loss in production and companion animals. Leptospirosis in dogs is prevalent worldwide and as well as a cause of canine disease, it presents a zoonotic risk to human contacts. Canine leptospirosis does not differ greatly from the syndromes seen in other animal species, with hepatic, renal, and pulmonary involvement being the main manifestations. While the pathogenesis of disease is well documented at the whole animal level, the cellular and molecular basis remains obscure. Killed, whole-cell bacterin vaccines are licensed worldwide and have not changed greatly over the past several decades. Vaccine-induced immunity is restricted to serologically related serovars and is generally short-lived, necessitating annual revaccination. The appearance of new serovars as causes of canine leptospirosis requires constant epidemiological surveillance and tailoring of vaccines to cover emerging serovars. At the present time, there is no realistic prospect of alternative, non-bacterin vaccines in the foreseeable future. Keywords: canine leptospirosis, vaccines, diagnosis, epidemiology, pathogenesis

  16. An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children.

    Science.gov (United States)

    Walker, Richard I

    2015-02-18

    Despite improvements to water quality, sanitation, and the implementation of current prevention and treatment interventions, diarrhea remains a major cause of illness and death, especially among children less than five years of age in the developing world. Rotavirus vaccines have already begun making a real impact on diarrhea, but several more enteric vaccines will be necessary to achieve broader reductions of illness and death. Among the many causes of diarrheal disease, enterotoxigenic Escherichia coli (ETEC) and Shigella are the two most important bacterial pathogens for which there are no currently licensed vaccines. Vaccines against these two pathogens could greatly reduce the impact of disease caused by these infections. This review describes the approaches to ETEC and Shigella vaccines that are currently under development, including a range of both cellular and subunit approaches for each pathogen. In addition, the review discusses strategies for maximizing the potential benefit of these vaccines, which includes the feasibility of co-administration, consolidation, and combination of vaccine candidates, as well as issues related to effective administration of enteric vaccines to infants. Recent impact studies indicate that ETEC and Shigella vaccines could significantly benefit global public health. Either vaccine, particularly if they could be combined together or with another enteric vaccine, would be an extremely valuable tool for saving lives and promoting the health of infants and children in the developing world, as well as potentially providing protection to travelers and military personnel visiting endemic areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Engineering Foot-and-Mouth Disease Viruses with Improved Growth Properties for Vaccine Development

    Science.gov (United States)

    Zheng, Haixue; Guo, Jianhong; Jin, Ye; Yang, Fan; He, Jijun; Lv, Lv; Zhang, Kesan; Wu, Qiong; Liu, Xiangtao; Cai, Xuepeng

    2013-01-01

    Background No licensed vaccine is currently available against serotype A foot-and-mouth disease (FMD) in China, despite the isolation of A/WH/CHA/09 in 2009, partly because this strain does not replicate well in baby hamster kidney (BHK) cells. Methodology/Principal Findings A novel plasmid-based reverse genetics system was used to construct a chimeric strain by replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09. The chimeric virus displayed growth kinetics similar to those of O/CHA/99 and was selected for use as a candidate vaccine strain after 12 passages in BHK cells. Cattle were vaccinated with the inactivated vaccine and humoral immune responses were induced in most of the animals on day 7. A challenge infection with A/WH/CHA/09 on day 28 indicated that the group given a 4-µg dose was fully protected and neither developed viremia nor seroconverted to a 3ABC antigen. Conclusions/Significance Our data demonstrate that the chimeric virus not only propagates well in BHK cells and has excellent antigenic matching against serotype A FMD, but is also a potential marker vaccine to distinguish infection from vaccination. These results suggest that reverse genetics technology is a useful tool for engineering vaccines for the prevention and control of FMD. PMID:23372840

  18. Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available Ebola virus (EBOV causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs. Currently, there are no licensed vaccines or therapeutics for human use. Recombinant vesicular stomatitis virus (rVSV-based vaccine vectors, which encode an EBOV glycoprotein in place of the VSV glycoprotein, have shown 100% efficacy against homologous Sudan ebolavirus (SEBOV or Zaire ebolavirus (ZEBOV challenge in NHPs. In addition, a single injection of a blend of three rVSV vectors completely protected NHPs against challenge with SEBOV, ZEBOV, the former Côte d'Ivoire ebolavirus, and Marburg virus. However, recent studies suggest that complete protection against the newly discovered Bundibugyo ebolavirus (BEBOV using several different heterologous filovirus vaccines is more difficult and presents a new challenge. As BEBOV caused nearly 50% mortality in a recent outbreak any filovirus vaccine advanced for human use must be able to protect against this new species. Here, we evaluated several different strategies against BEBOV using rVSV-based vaccines. Groups of cynomolgus macaques were vaccinated with a single injection of a homologous BEBOV vaccine, a single injection of a blended heterologous vaccine (SEBOV/ZEBOV, or a prime-boost using heterologous SEBOV and ZEBOV vectors. Animals were challenged with BEBOV 29-36 days after initial vaccination. Macaques vaccinated with the homologous BEBOV vaccine or the prime-boost showed no overt signs of illness and survived challenge. In contrast, animals vaccinated with the heterologous blended