WorldWideScience

Sample records for acam2000 smallpox vaccine

  1. 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of a pool of vaccinia virus strains with varying degrees of virulence, and was grown on the skin of calves, an outdated technique that poses an unnecessary risk of contamination.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®, ACAM2000vaccination 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

  2. Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.

    Science.gov (United States)

    Berhanu, Aklile; Prigge, Jonathan T; Silvera, Peter M; Honeychurch, Kady M; Hruby, Dennis E; Grosenbach, Douglas W

    2015-07-01

    The therapeutic efficacies of smallpox vaccine ACAM2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. Postexposure administration of ACAM2000 alone did not provide any protection against severe monkeypox disease or mortality. In contrast, postexposure treatment with tecovirimat alone or in combination with ACAM2000 provided full protection. Additionally, tecovirimat treatment delayed until day 4, 5, or 6 postinfection was 83% (days 4 and 5) or 50% (day 6) effective.

  3. Human antibody responses to the polyclonal Dryvax vaccine for smallpox prevention can be distinguished from responses to the monoclonal replacement vaccine ACAM2000.

    Science.gov (United States)

    Pugh, Christine; Keasey, Sarah; Korman, Lawrence; Pittman, Phillip R; Ulrich, Robert G

    2014-06-01

    Dryvax (Wyeth Laboratories, Inc., Marietta, PA) is representative of the vaccinia virus preparations that were previously used for preventing smallpox. While Dryvax was highly effective, the national supply stocks were depleted, and there were manufacturing concerns regarding sterility and the clonal heterogeneity of the vaccine. ACAM2000 (Acambis, Inc./Sanofi-Pasteur Biologics Co., Cambridge, MA), a single-plaque-purified vaccinia virus derivative of Dryvax, recently replaced the polyclonal smallpox vaccine for use in the United States. A substantial amount of sequence heterogeneity exists within the polyclonal proteome of Dryvax, including proteins that are missing from ACAM2000. Reasoning that a detailed comparison of antibody responses to the polyclonal and monoclonal vaccines may be useful for identifying unique properties of each antibody response, we utilized a protein microarray comprised of approximately 94% of the vaccinia poxvirus proteome (245 proteins) to measure protein-specific antibody responses of 71 individuals receiving a single vaccination with ACAM2000 or Dryvax. We observed robust antibody responses to 21 poxvirus proteins in vaccinated individuals, including 11 proteins that distinguished Dryvax responses from ACAM2000. Analysis of protein sequences from Dryvax clones revealed amino acid level differences in these 11 antigenic proteins and suggested that sequence variation and clonal heterogeneity may contribute to the observed differences between Dryvax and ACAM2000 antibody responses.

  4. ACAM2000(TM): The New Smallpox Vaccine for United States Strategic National Stockpile

    Science.gov (United States)

    2010-01-01

    lupus erythematosus . Am J Med. 1990;89(4):411–419. 53. Woodruff JF. Viral myocarditis. A review. Am J Pathol. 1980;101(2): 425–484. 54. Berhanu A, King...attempting to limit vaccination to those without immunodeficiencies, eczema, or pregnancy . Among 730,580 DOD vaccinees, three cases of post... lupus , or infections such as HIV or parvovirus B19.49 Interestingly, patients with lupus or parvovirus B19 infections are predisposed to myocarditis

  5. Smallpox vaccine, ACAM2000: Sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response.

    Science.gov (United States)

    Pittman, Phillip R; Garman, Patrick M; Kim, Sung-Han; Schmader, Trevor J; Nieding, William J; Pike, Jason G; Knight, Ryan; Johnston, Sara C; Huggins, John W; Kortepeter, Mark G; Korman, Lawrence; Ranadive, Manmohan; Quinn, Xiaofei; Meyers, Mitchell S

    2015-06-12

    The U.S. Department of Defense vaccinates personnel deployed to high-risk areas with the vaccinia virus (VACV)-based smallpox vaccine. Autoinoculations and secondary and tertiary transmissions due to VACV shedding from the vaccination site continue to occur despite education of vaccinees on the risks of such infections. The objectives of this study were to investigate, in naïve smallpox vaccinees, (a) whether the vaccination site can remain contagious after the scab separates and (b) whether the application of povidone iodine ointment (PIO) to the vaccination site inactivates VACV without affecting the immune response. These objectives were tested in 60 individuals scheduled to receive smallpox vaccine. Thirty individuals (control) did not receive PIO; 30 subjects (treatment) received PIO starting on post-vaccination day 7. Counter to current dogma, this study showed that VACV continues to shed from the vaccination site after the scab separates. Overall viral shedding levels in the PIO group were significantly lower than those in the control group (p=0.0045), and PIO significantly reduced the duration of viral shedding (median duration 14.5 days and 21 days in the PIO and control groups, respectively; p=0.0444). At least 10% of control subjects continued to shed VACV at day 28, and 3.4% continued to shed the virus at day 42. PIO reduced the proportion of subjects shedding virus from the vaccination site from day 8 until days 21-23 compared with control subjects. Groups did not differ significantly in the proportion of subjects mounting an immune response, as measured by neutralizing antibodies, IgM, IgG, and interferon-gamma enzyme-linked immunospot assay. When applied to the vaccination site starting on day 7, PIO reduced viral shedding without altering the immune response. The use of PIO in addition to a semipermeable dressing may reduce the rates of autoinoculation and contact transmission originating from the vaccination site in smallpox-vaccinated individuals.

  6. New smallpox vaccines for an ancient scourge.

    Science.gov (United States)

    Frey, Sharon E

    2014-01-01

    The potential use of variola virus, a Class A agent of bioterrorism, remains a concern. In an effort to prepare for a possible smallpox outbreak due to an intentional release of variola, the U.S. government and industry have been evaluating vaccines stored in the National Strategic Stockpile including cell culture grown ACAM2000 and modified vaccinia Ankara, IMVAMUNE, in clinical studies. This paper discusses smallpox vaccines studies conducted at the Saint Louis University Center for Vaccine Development.

  7. 76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

    Science.gov (United States)

    2011-08-11

    ... cell culture technology under modern manufacturing practices and standards. Both ACAM2000 and Dryvax... response to smallpox vaccines and development of animal models for demonstration of effectiveness of next...-generation smallpox vaccines were prepared on the skin of calves or other animals or in chicken eggs...

  8. Clinical guidance for smallpox vaccine use in a postevent vaccination program.

    Science.gov (United States)

    Petersen, Brett W; Damon, Inger K; Pertowski, Carol A; Meaney-Delman, Dana; Guarnizo, Julie T; Beigi, Richard H; Edwards, Kathryn M; Fisher, Margaret C; Frey, Sharon E; Lynfield, Ruth; Willoughby, Rodney E

    2015-02-20

    This report outlines recommendations for the clinical use of the three smallpox vaccines stored in the U.S. Strategic National Stockpile for persons who are exposed to smallpox virus or at high risk for smallpox infection during a postevent vaccination program following an intentional or accidental release of the virus. No absolute contraindications exist for smallpox vaccination in a postevent setting. However, several relative contraindications exist among persons with certain medical conditions. CDC recommendations for smallpox vaccine use were developed in consideration of the risk for smallpox infection, risk for an adverse event following vaccination, and benefit from vaccination. Smallpox vaccines are made from live vaccinia viruses that protect against smallpox disease. They do not contain variola virus, the causative agent of smallpox. The three smallpox vaccines stockpiled are ACAM2000, Aventis Pasteur Smallpox Vaccine (APSV), and Imvamune. Surveillance and containment activities including vaccination with replication-competent smallpox vaccine (i.e., vaccine viruses capable of replicating in mammalian cells such as ACAM2000 and APSV) will be the primary response strategy for achieving epidemic control. Persons exposed to smallpox virus are at high risk for developing and transmitting smallpox and should be vaccinated with a replication-competent smallpox vaccine unless severely immunodeficient. Because of a high likelihood of a poor immune response and an increased risk for adverse events, smallpox vaccination should be avoided in persons with severe immunodeficiency who are not expected to benefit from vaccine, including bone marrow transplant recipients within 4 months of transplantation, persons infected with HIV with CD4 cell counts smallpox virus exposure in persons with severe immunodeficiency. Persons without a known smallpox virus exposure might still be at high risk for developing smallpox infection depending on the magnitude of the outbreak and

  9. Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses - Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015.

    Science.gov (United States)

    Petersen, Brett W; Harms, Tiara J; Reynolds, Mary G; Harrison, Lee H

    2016-03-18

    On June 25, 2015, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination with live smallpox (vaccinia) vaccine (ACAM2000) for laboratory personnel who directly handle 1) cultures or 2) animals contaminated or infected with replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains (i.e., those that are capable of causing clinical infection and producing infectious virus in humans), or other orthopoxviruses that infect humans (e.g., monkeypox, cowpox, and variola) (recommendation category: A, evidence type 2 [Box]). Health care personnel (e.g., physicians and nurses) who currently treat or anticipate treating patients with vaccinia virus infections and whose contact with replication-competent vaccinia viruses is limited to contaminated materials (e.g., dressings) and persons administering ACAM2000 smallpox vaccine who adhere to appropriate infection prevention measures can be offered vaccination with ACAM2000 (recommendation category: B, evidence type 2 [Box]). These revised recommendations update the previous ACIP recommendations for nonemergency use of vaccinia virus smallpox vaccine for laboratory and health care personnel at risk for occupational exposure to orthopoxviruses (1). Since 2001, when the previous ACIP recommendations were developed, ACAM2000 has replaced Dryvax as the only smallpox vaccine licensed by the U.S. Food and Drug Administration (FDA) and available for use in the United States (2). These recommendations contain information on ACAM2000 and its use in laboratory and health care personnel at risk for occupational exposure to orthopoxviruses.

  10. The strategic use of novel smallpox vaccines in the post-eradication world.

    Science.gov (United States)

    Golden, Joseph W; Hooper, Jay W

    2011-07-01

    We still face a threat of orthopoxviruses in the form of biological weapons and emerging zoonoses. Therefore, there is a need to maintain a comprehensive defense strategy to counter the low-probability, high-impact threat of smallpox, as well as the ongoing threat of naturally occurring orthopoxvirus disease. The currently licensed live-virus smallpox vaccine ACAM2000 is effective, but associated with serious and even life-threatening adverse events. The health threat posed by this vaccine, and other previously licensed vaccines, has prevented many first responders, and even many in the military, from receiving a vaccine against smallpox. At the same time, global immunity produced during the smallpox eradication campaign is waning. Here, we review novel subunit/component vaccines and how they might play roles in unconventional strategies to defend against emerging orthopoxvirus diseases throughout the world and against smallpox used as a weapon of mass destruction.

  11. Smallpox vaccine revisited.

    Science.gov (United States)

    Capriotti, Teri

    2002-12-01

    Smallpox is a serious contagious disease which is back in the public eye. Yet, most health care providers are unprepared for its return. Nurses will be key health care professionals in a smallpox outbreak or vaccination program.

  12. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    Science.gov (United States)

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

  13. Impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients.

    Science.gov (United States)

    Kennedy, Richard B; Poland, Gregory A; Ovsyannikova, Inna G; Oberg, Ann L; Asmann, Yan W; Grill, Diane E; Vierkant, Robert A; Jacobson, Robert M

    2016-06-14

    Smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. Smallpox vaccine efficacy was historically defined by the appearance of a lesion or "take" at the vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax(®) or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the smallpox vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated smallpox vaccines and/or effective antiviral therapy targets against poxvirus infections.

  14. 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.

  15. 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 ...

  16. Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus.

    Science.gov (United States)

    Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark

    2014-11-01

    Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered

  17. Recent advances in the study of live attenuated cell-cultured smallpox vaccine LC16m8.

    Science.gov (United States)

    Eto, Akiko; Saito, Tomoya; Yokote, Hiroyuki; Kurane, Ichiro; Kanatani, Yasuhiro

    2015-11-01

    LC16m8 is a live, attenuated, cell-cultured smallpox vaccine that was developed and licensed in Japan in the 1970s, but was not used in the campaign to eradicate smallpox. In the early 2000s, the potential threat of bioterrorism led to reconsideration of the need for a smallpox vaccine. Subsequently, LC16m8 production was restarted in Japan in 2002, requiring re-evaluation of its safety and efficacy. Approximately 50,000 children in the 1970s and about 3500 healthy adults in the 2000s were vaccinated with LC16m8 in Japan, and 153 adults have been vaccinated with LC16m8 or Dryvax in phase I/II clinical trials in the USA. These studies confirmed the safety and efficacy of LC16m8, while several studies in animal models have shown that LC16m8 protects the host against viral challenge. The World Health Organization Strategic Advisory Group of Experts on Immunization recommended LC16m8, together with ACAM2000, as a stockpile vaccine in 2013. In addition, LC16m8 is expected to be a viable alternative to first-generation smallpox vaccines to prevent human monkeypox.

  18. Traditional Smallpox Vaccines and Atopic Dermatitis

    Science.gov (United States)

    ... Trials 2016 Research Grant Request DONATE Traditional Smallpox Vaccines and Atopic Dermatitis Frequently Asked Questions Eczema Living ... Involved Eczema Products News Research Donate Traditional Smallpox Vaccines and Atopic Dermatitis Frequently Asked Questions What is ...

  19. Defending against smallpox: a focus on vaccines.

    Science.gov (United States)

    Voigt, Emily A; Kennedy, Richard B; Poland, Gregory A

    2016-09-01

    Smallpox has shaped human history, from the earliest human civilizations well into the 20th century. With high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. The eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. Concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued vaccine development. Smallpox vaccine development is thus a much-reviewed topic of high interest. This review focuses on the current state of smallpox vaccines and their context in biodefense efforts.

  20. The immunology of smallpox vaccines.

    Science.gov (United States)

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

    2009-06-01

    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.

  1. Cytokine production associated with smallpox vaccine responses.

    Science.gov (United States)

    Simon, Whitney L; Salk, Hannah M; Ovsyannikova, Inna G; Kennedy, Richard B; Poland, Gregory A

    2014-01-01

    Smallpox was eradicated 34 years ago due to the success of the smallpox vaccine; yet, the vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current smallpox vaccines. Interindividual variations in vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the smallpox vaccine compared with other vaccines. Here, we aim to summarize the cytokine responses associated with smallpox vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to smallpox vaccination.

  2. 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.

  3. 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.

  4. Smallpox vaccination and bioterrorism with pox viruses.

    Science.gov (United States)

    Mayr, Anton

    2003-10-01

    Bioterrorist attacks occupy a special place amongst the innumerable potential types of terrorist attack, with the intentional release of pox viruses being especially feared in this connection. Apart from the variola virus, the agent responsible for smallpox in humans, the monkeypox virus and numerous other animal pox viruses pose potential risks for humans and animals. This risk scenario also includes recombinations between the various pox viruses, changes in hosts and genetically engineered manipulations of pox viruses. For over 200 years, the method of choice for combatting smallpox was via vaccination with a reproductive, original vaccinia virus. Worldwide eradication of smallpox at the end of the 1970s and the discontinuation of routine smallpox vaccination in 1980 can be credited to such vaccination. Unfortunately, these vaccinations were associated with a large number of postvaccinal impairments, sometimes resulting in death (e.g. postvaccinal encephalitis). The only way to restrict such postvaccinal complications was to carry out initial vaccination within the first 2 postnatal years. Initial vaccination at a later age led to such a sharp increase in the number of vaccines with complications that vaccination had to be discouraged. The dilemma of the smallpox vaccine stocks stems from the fact that a large portion of these stocks are produced with the same vaccinia strains as before. This is irresponsible, especially as the percentage of immune-suppressed persons in the population, for whom vaccination-related complications pose an especial threat, is increasing. One solution to the dilemma of the smallpox vaccine stocks is the MVA strain. It is harmless, protects humans and animals equally well against smallpox and can be applied parenterally.

  5. Poxviruses: smallpox vaccine, its complications and chemotherapy

    Directory of Open Access Journals (Sweden)

    Mimi Remichkova

    2010-04-01

    Full Text Available Mimi RemichkovaDepartment of Pathogenic Bacteria, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, BulgariaAbstract: The threat of bioterrorism in the recent years has once again posed to mankind the unresolved problems of contagious diseases, well forgotten in the past. Smallpox (variola is among the most dangerous and highly contagious viral infections affecting humans. The last natural case in Somalia marked the end of a successful World Health Organization campaign for smallpox eradication by vaccination on worldwide scale. Smallpox virus still exists today in some laboratories, specially designated for that purpose. The contemporary response in the treatment of the post-vaccine complications, which would occur upon enforcing new programs for mass-scale smallpox immunization, includes application of effective chemotherapeutics and their combinations. The goals are to provide the highest possible level of protection and safety of the population in case of eventual terrorist attack. This review describes the characteristic features of the poxviruses, smallpox vaccination, its adverse reactions, and poxvirus chemotherapy.Keywords: poxvirus, smallpox vaccine, post vaccine complications, inhibitors

  6. Third-generation smallpox vaccines: challenges in the absence of clinical smallpox.

    Science.gov (United States)

    Meseda, Clement A; Weir, Jerry P

    2010-09-01

    Smallpox, a disease caused by variola virus, is estimated to have killed hundreds of millions to billions of people before it was certified as eradicated in 1980. However, there has been renewed interest in smallpox vaccine development due in part to zoonotic poxvirus infections and the possibility of a re-emergence of smallpox, as well as the fact that first-generation smallpox vaccines are associated with relatively rare, but severe, adverse reactions in some vaccinees. An understanding of the immune mechanisms of vaccine protection and the use of suitable animal models for vaccine efficacy assessment are paramount to the development of safer and effective smallpox vaccines. This article focuses on studies aimed at understanding the immune responses elicited by vaccinia virus and the various animal models that can be used to evaluate smallpox vaccine efficacy. Harnessing this information is necessary to assess the effectiveness and potential usefulness of new-generation smallpox vaccines.

  7. 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.

  8. 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....

  9. Emergence and reemergence of smallpox: the need for development of a new generation smallpox vaccine.

    Science.gov (United States)

    Shchelkunov, Sergei N

    2011-12-30

    The review summarizes the archive data on smallpox, history of ancient civilizations, and the most recent data on the genome organization of orthopoxviruses, their evolutionary relationships, and the time points of smallpox emergence. The performed analysis provides the grounds for the hypothesis that smallpox could have emerged several times as a result of evolutionary changes in the zoonotic ancestor virus and disappeared due to insufficient population size of ancient civilizations. Smallpox reemerged in the Indian subcontinent approximately 2500-3000 years before present, which resulted in endemization of this anthroponotic infection, which had been preserved until the smallpox eradication in the 20th century AD. The conclusion suggests a potential possibility of future variola virus reemergence, presenting a great menace for mankind, as well as the need for development of new safe smallpox vaccines, design of anti-smallpox drugs, and activation of the control of zoonotic human orthopoxvirus infections.

  10. Cutaneous responses to vaccinia in individuals with previous smallpox vaccination.

    Science.gov (United States)

    Simpson, Eric L; Hercher, Michelle; Hammarlund, Erika K; Lewis, Matthew W; Slifka, Mark K; Hanifin, Jon M

    2007-09-01

    The durability of immune responses to smallpox vaccine is a subject of considerable debate. We compared cutaneous vaccinia responses in patients vaccinated in the distant past with vaccine-naïve individuals using serial close-up photographs. The previously vaccinated group had a significantly reduced time course and milder cutaneous reactions. Vaccinated individuals appear to maintain clinically detectable immunity against vaccinia for at least 20 years after smallpox vaccination.

  11. Smallpox vaccine: the good, the bad, and the ugly.

    Science.gov (United States)

    Belongia, Edward A; Naleway, Allison L

    2003-04-01

    Smallpox inarguably shaped the course of human history by killing countless millions in both the Old World and the New World. Dr. Edward Jenner's discovery of vaccination in the late 18th century, and the global eradication of smallpox in the 1970s, rank among the greatest achievements in human history. Amidst recent growing concerns about bioterrorism, smallpox vaccination has resurfaced from the history books to become a topic of major importance. Inoculation with vaccinia virus is highly effective for the prevention of smallpox infection, but it is associated with several known side effects that range from mild and self-limited to severe and life-threatening. As the United States moves forward with plans to vaccinate selected health care workers and the military, and perhaps offer the vaccination to all citizens in the future, it is important to fully understand and appreciate the history, risks, and benefits of smallpox vaccination.

  12. Genomic sequence and analysis of a vaccinia virus isolate from a patient with a smallpox vaccine-related complication

    Directory of Open Access Journals (Sweden)

    Damon Inger

    2006-10-01

    Full Text Available Abstract Background Vaccinia virus (VACV-DUKE was isolated from a lesion on a 54 year old female who presented to a doctor at the Duke University Medical Center. She was diagnosed with progressive vaccinia and treated with vaccinia immune globulin. The availability of the VACV-DUKE genome sequence permits a first time genomic comparison of a VACV isolate associated with a smallpox vaccine complication with the sequence of culture-derived clonal isolates of the Dryvax vaccine. Results This study showed that VACV-DUKE is most similar to VACV-ACAM2000 and CLONE3, two VACV clones isolated from the Dryvax® vaccine stock confirming VACV-DUKE as an isolate from Dryvax®. However, VACV-DUKE is unique because it is, to date, the only Dryvax® clone isolated from a patient experiencing a vaccine-associated complication. The 199,960 bp VACV-DUKE genome encodes 225 open reading frames, including 178 intact genes and 47 gene fragments. Between VACV-DUKE and the other Dryvax® isolates, the major genomic differences are in fragmentation of the ankyrin-like, and kelch-like genes, presence of a full-length Interferon-α/β receptor gene, and the absence of a duplication of 12 ORFs in the inverted terminal repeat. Excluding this region, the DNA sequence of VACV-DUKE differs from the other two Dryvax® isolates by less than 0.4%. DNA sequencing also indicated that there was little heterogeneity in the sample, supporting the hypothesis that virus from an individual lesion is clonal in origin despite the fact that the vaccine is a mixed population. Conclusion Virus in lesions that result from progressive vaccinia following vaccination with Dryvax are likely clonal in origin. The genomic sequence of VACV-DUKE is overall very similar to that of Dryvax® cell culture-derived clonal isolates. Furthermore, with the sequences of multiple clones from Dryvax® we can begin to appreciate the diversity of the viral population in the smallpox vaccine.

  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. 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. PMID:22860117

  15. Epidemiologic Assessment of the Protective Effects of Smallpox Vaccination

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    2006-01-01

    Full Text Available Despite smallpox eradication, the widely discussed possibility of a bioterrorist attack using a variola virus makes it necessary to review the epidemiology of smallpox and the effects of various vaccination schemes. This paper provides a literature review concerning the epidemiologic assessment of the protective effects of smallpox vaccination, with particular emphasis on the statistical and theoretical points of view. Although smallpox vaccination has the longest history of all vaccinations, we lack precise epidemiologic estimates of its effectiveness. Vaccination practice continually evolved and many places experienced vaccinations with various strains over time. Despite the weak statistical evidence, it can be stated with certainty that smallpox vaccines prevented infection for a few decades after primary vaccination and that vaccinated individuals had the benefit of a longer lasting partial protection when they contracted the disease. Confronted with the huge uncertainties and with the necessity to rely on laboratory evidence, appropriate preparedness plans for countermeasures using vaccination must be based on the best available evidence.

  16. 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.

  17. [Immunological characteristics of the 2-stage method of smallpox vaccination].

    Science.gov (United States)

    Marennikova, S S; Matsevich, G R; Sokolova, A F; Shul'ga, L G; Manenkova, G M

    1977-05-01

    As a result of observations carried out on children the authors present immunological characteristics of two-stage smallpox vaccination at different intervals (1 to 60 days) between the injection of inactivated and live vaccine. There proved to be acceleration and intensification of antibody formation after two-stage immunization in comparison with the rutine vaccination. A seven-day interval between the injection of the inactivated and live preparations was recommended on the basis of the data obtained.

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

    NARCIS (Netherlands)

    Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

    2006-01-01

    There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known ab

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

    NARCIS (Netherlands)

    Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

    2006-01-01

    There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known ab

  20. Should smallpox vaccine be made available to the general public?

    Science.gov (United States)

    May, Thomas; Silverman, Ross D

    2003-06-01

    In June 2002, the Advisory Committee on Immunization Practices (ACIP) approved draft recommendations concerning preparation for potential biological terror attacks that utilize the smallpox virus. ACIP recommends against both mandatory and voluntary vaccination of the general public. The present paper examines the moral and political considerations both for and against each of the general public vaccination options considered by the ACIP in the context of the state's authority over vaccination for the purposes of protecting public health. Although it is clear that compulsory mass vaccination is not justified at this time, the issues surrounding voluntary vaccination are more complex. Should smallpox vaccination prior to an outbreak be made available to the general public? The paper concludes that the vaccine should not be made available at this time. This conclusion, however, is based upon contingent features of current circumstances, which would change once an outbreak occurred. In the even of a terror-related outbreak of smallpox, the general public's access to voluntary vaccination would become justified, even in areas beyond where the outbreak has occurred.

  1. What is Smallpox?

    Science.gov (United States)

    ... this page: About CDC.gov . Smallpox About Smallpox History of Smallpox Spread and Eradication of Smallpox Transmission Signs and Symptoms Prevention and Treatment Smallpox Vaccine Basics Vaccine Safety Side Effects of Vaccination Who Should Get a Smallpox Vaccination? Bioterrorism The ...

  2. Group interest versus self-interest in smallpox vaccination policy.

    Science.gov (United States)

    Bauch, Chris T; Galvani, Alison P; Earn, David J D

    2003-09-02

    The recent threat of bioterrorism has fueled debate on smallpox vaccination policy for the United States. Certain policy proposals call for voluntary mass vaccination; however, if individuals decide whether to vaccinate according to self-interest, the level of herd immunity achieved may differ from what is best for the population as a whole. We present a synthesis of game theory and epidemic modeling that formalizes this conflict between self-interest and group interest and shows that voluntary vaccination is unlikely to reach the group-optimal level. This shortfall results in a substantial increase in expected mortality after an attack.

  3. [The history of smallpox vaccination in the Imperial Moscow foster house].

    Science.gov (United States)

    Sher, S A

    2011-01-01

    The article deals with the history of vaccination against natural smallpox which is directly connected to the Imperial Moscow foster house which became one of smallpox vaccination centers in Russia of XIX century. In 1801, when variolations were substituted by more safe cowpox vaccinations, in Russia the first vaccination using the method of Jenner was made exactly in in the Imperial Moscow foster house. From 1805, the smallpox vaccination received the status of force of law, the Imperial Moscow foster house began to produce and to distribute the smallpox vaccine all over the country and apply the smallpox vaccination not only to its foster children but to all turned to and, besides that, to train the smallpox vaccination. In 1857, the Imperial Moscow foster house became the first establishment in Russia where the revaccination was applied. In 1980, the WHO proclaimed that the implementation of the global program of smallpox irradiation resulted in the natural smallpox elimination on Earth. The smallpox became the first communicable disease defeated due to mass vaccination. One third of Earth population was vaccinated by the Soviet vaccine, which originated mainly because of the activities of physicians of the Imperial Moscow foster house.

  4. Outbreaks of human monkeypox after cessation of smallpox vaccination.

    Science.gov (United States)

    Reynolds, Mary G; Damon, Inger K

    2012-02-01

    The recent observation of a surge in human monkeypox in the Democratic Republic of the Congo (DRC) prompts the question of whether cessation of smallpox vaccination is driving the phenomenon, and if so, why is re-emergence not universal throughout the historic geographic range of the virus? Research addressing the virus's mechanisms for immune evasion and induction, as well as that directed at elucidating the genes involved in pathogenesis in different viral lineages (West African vs Congo Basin), provide insights to help explain why emergence appears to be geographically limited. Novel vaccines offer one solution to curtail the spread of this disease.

  5. 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...

  6. 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...

  7. 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.

  8. Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens.

    Science.gov (United States)

    Sakhatskyy, Pavlo; Wang, Shixia; Zhang, Chuanyou; Chou, Te-Hui; Kishko, Michael; Lu, Shan

    2008-02-05

    The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on VARV antigen sequences to induce immunity against poxvirus infection.

  9. 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.

  10. 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.

  11. Smallpox

    Science.gov (United States)

    ... samples saved for government research. Researchers continue to debate whether or not to kill the last remaining ... biological weapon It is unknown how long past vaccinations stay effective. People who received the vaccine many ...

  12. Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model

    Directory of Open Access Journals (Sweden)

    Portnoy Diane L

    2004-08-01

    Full Text Available Abstract Background Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. Methods We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. Results We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. Conclusions Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity and should be accompanied by increased public awareness and surveillance.

  13. TLR3 and TLR9 agonists improve postexposure vaccination efficacy of live smallpox vaccines.

    Science.gov (United States)

    Israely, Tomer; Melamed, Sharon; Achdout, Hagit; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

    2014-01-01

    Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination.

  14. TLR3 and TLR9 agonists improve postexposure vaccination efficacy of live smallpox vaccines.

    Directory of Open Access Journals (Sweden)

    Tomer Israely

    Full Text Available Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV, a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs were less protective than the TLR3 agonist poly(I:C. We show that activation of type 1 IFN by poly(I:C and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination.

  15. A vaccinia virus renaissance: new vaccine and immunotherapeutic uses after smallpox eradication.

    Science.gov (United States)

    Verardi, Paulo H; Titong, Allison; Hagen, Caitlin J

    2012-07-01

    In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity against related orthopoxviruses, including smallpox virus (variola virus). Over time, vaccinia virus (VACV) replaced cowpox virus as the smallpox vaccine, and vaccination efforts eventually led to the successful global eradication of smallpox in 1979. VACV has many characteristics that make it an excellent vaccine and that were crucial for the successful eradication of smallpox, including (1) its exceptional thermal stability (a very important but uncommon characteristic in live vaccines), (2) its ability to elicit strong humoral and cell-mediated immune responses, (3) the fact that it is easy to propagate, and (4) that it is not oncogenic, given that VACV replication occurs exclusively within the host cell cytoplasm and there is no evidence that the viral genome integrates into the host genome. Since the eradication of smallpox, VACV has experienced a renaissance of interest as a viral vector for the development of recombinant vaccines, immunotherapies, and oncolytic therapies, as well as the development of next-generation smallpox vaccines. This revival is mainly due to the successful use and extensive characterization of VACV as a vaccine during the smallpox eradication campaign, along with the ability to genetically manipulate its large dsDNA genome while retaining infectivity and immunogenicity, its wide mammalian host range, and its natural tropism for tumor cells that allows its use as an oncolytic vector. This review provides an overview of new uses of VACV that are currently being explored for the development of vaccines, immunotherapeutics, and oncolytic virotherapies.

  16. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

    Directory of Open Access Journals (Sweden)

    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.

  17. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

    Directory of Open Access Journals (Sweden)

    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.

  18. Attitudes of healthcare workers in U.S. hospitals regarding smallpox vaccination

    Directory of Open Access Journals (Sweden)

    O'Brien Megan A

    2003-06-01

    Full Text Available Abstract Background The United States is implementing plans to immunize 500,000 hospital-based healthcare workers against smallpox. Vaccination is voluntary, and it is unknown what factors drive vaccine acceptance. This study's aims were to estimate the proportion of workers willing to accept vaccination and to identify factors likely to influence their decisions. Methods The survey was conducted among physicians, nurses, and others working primarily in emergency departments or intensive care units at 21 acute-care hospitals in 10 states during the two weeks before the U.S. national immunization program for healthcare workers was announced in December 2002. Of the questionnaires distributed, 1,165 were returned, for a response rate of 81%. The data were analyzed by logistic regression and were adjusted for clustering within hospital and for different number of responses per hospital, using generalized linear mixed models and SAS's NLMIXED procedure. Results Sixty-one percent of respondents said they would definitely or probably be vaccinated, while 39% were undecided or inclined against it. Fifty-three percent rated the risk of a bioterrorist attack using smallpox in the United States in the next two years as either intermediate or high. Forty-seven percent did not feel well-informed about the risks and benefits of vaccination. Principal concerns were adverse reactions and the risk of transmitting vaccinia. In multivariate analysis, four variables were associated with willingness to be vaccinated: perceived risk of an attack, self-assessed knowledge about smallpox vaccination, self-assessed previous smallpox vaccination status, and gender. Conclusions The success of smallpox vaccination efforts will ultimately depend on the relative weight in people's minds of the risk of vaccine adverse events compared with the risk of being exposed to the disease. Although more than half of the respondents thought the likelihood of a bioterrorist smallpox

  19. Smallpox, risks of terrorist attacks, and the Nash equilibrium: an introduction to game theory and an examination of the smallpox vaccination program.

    Science.gov (United States)

    Hamilton, Richard; McCain, Roger

    2009-01-01

    The smallpox vaccination emergency preparedness program has been unsuccessful in enrolling sufficient numbers of healthcare workers. The objective of this study was to use game theory to analyze a pre-event vaccination versus post-event vaccination program using the example of a terrorist considering an attack with smallpox or a hoax. A three-person game (normal and extensive form), and an in-person game are played for pre-event and post-event vaccinations of healthcare workers facing the possibility of a smallpox attack or hoax. Full pre-event vaccinations of all targeted healthcare workers are not necessary to deter a terrorist attack. In addition, coordinating vaccinations among healthcare workers, individual healthcare worker risk aversion, and the degree to which terrorists make the last move based on specific information on the status of pre-event vaccination all greatly impact strategy selection for both sides. A Nash Equilibrium of pre- and post-event vaccination strategies among a large number of healthcare professionals will tend to eliminate the advantage (of the terrorists) of a smallpox attack over a hoax, but may not eliminate some probability of a smallpox attack. Emergency preparedness would benefit from game theory analysis of the costs and payoffs of specific terrorism/counter-terrorism strategies.

  20. Safety of attenuated smallpox vaccine LC16m8 in immunodeficient mice.

    Science.gov (United States)

    Yokote, Hiroyuki; Shinmura, Yasuhiko; Kanehara, Tomomi; Maruno, Shinichi; Kuranaga, Masahiko; Matsui, Hajime; Hashizume, So

    2014-09-01

    Freeze-dried live attenuated smallpox vaccine LC16m8 prepared in cell culture has been the sole smallpox vaccine licensed in Japan since 1975 and was recently recommended as a WHO stockpile vaccine. We evaluated the safety of recently remanufactured lots of LC16m8 using a series of immunodeficient mouse models. These models included suckling mice, severe combined immunodeficiency disease (SCID) mice, and wild-type mice treated with cyclosporine. LC16m8 showed extremely low virulence in each of the three mouse models compared with that of its parental strains, Lister and LC16mO. These results provide further evidence that LC16m8 is one of the safest replication-competent smallpox vaccines in the world and may be considered for use in immunodeficient patients.

  1. [Study of allergic reactions in the body after experimental smallpox vaccination].

    Science.gov (United States)

    Vorob'ev, A A; Afanas'ev, S S; Patrikeev, G T; Prigoda, A S; Podkuiĭko, V N

    1977-09-01

    Experiments on guinea pigs demonstrated a mixed cellular-humoral character of allergy in smallpox vaccination. The ratio of cellular and humoral components depended on the site of the vaccina application. Skin manifestations in smallpox vaccination (hyperemia, infiltration, papula) were due to the multiplication of the virus proper, increased sensitivity of the surrounding tissues to the live vibrio, and specific immunological reconstruction. The skin of the sensitized animal after the anaphylactic shock in response to the intracardiac injection of the challenging dose of the vaccine virus acquired areactivity to its subsequent application.

  2. 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.

  3. Progress in the research of smallpox vaccines%天花疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    孟昕; 阮力

    2010-01-01

    In the last decade, the research on smallpox vaccine has been paid much more attention because of the special position of variola virus in bioterrorism and biological warfare. To date, 4 generations of smallpox vaccines have been developed, and of which 3 generations can be used. Among them, the first generation smallpox vaccines play an important role in the achievement of global smallpox eradication, but their adverse reactions are strong. The second generation smallpox vaccines possess the theoretical advantages conferred by improved manufacturing process and lowered risk of contamination by adventitious agents. The third generation smallpox vaccines have reduced virulence and improved safety, but the immunological efficacy has also descended. The fourth generation smallpox vaccines are developed by techniques for genetic engineering, and the efficacy remains to be evaluated. Owing to global smallpox eradication, the evaluation of the immunological efficacy of new smallpox vaccines becomes the key procedure which can hinder the development of new vaccines.%鉴于天花病毒在生物恐怖和生物战中的特殊地位,近十年来,天花疫苗的研究重新得到重视.到目前为止,天花疫苗研究已进入第四代,已有三代天花疫苗可供使用.其中,第一代天花疫苗在全球消灭天花中起到重要和关键的作用,但不良反应较强.第二代疫苗改进了生产工艺,降低了外源因子污染的可能.第三代疫苗有效地降低了疫苗的毒力,增强了安全性,但免疫效力有所下降.第四代疫苗系使用基因工程技术研制的疫苗,效果尚待评价.由于天花已经消灭,在新疫苗的研究中,如何评价其免疫效果成为妨碍疫苗研究进展的关键环节.

  4. The discontinuation of routine smallpox vaccination in the United States, 1960-1976: an unlikely affirmation of biomedical hegemony.

    Science.gov (United States)

    Rich, Miriam

    2011-02-01

    This article seeks to understand the discursive context of the cessation of routine smallpox vaccination in the United States in the early 1970s. The United States has a long tradition of opposition to compulsory smallpox vaccination, usually expressed in terms of concerns about personal liberties, the extent of state authority, and challenges to the hegemony of orthodox biomedicine. The practice of routine smallpox vaccination continued in the United States until its termination in the 1970s, following a 1971 recommendation against the practice issued by the United States Public Health Service. This history investigates the ways in which opposition to compulsory smallpox vaccination in the 1960s and 70s was articulated and understood by contemporaries through an analysis of the rhetoric used in leading medical journals and popular newspapers. It finds that this ultimately successful movement to end routine smallpox vaccination drew upon the language of biomedical authority rather than political protest.

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

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Sørup, Signe;

    2016-01-01

    BACKGROUND: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vacc......BACKGROUND: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested...

  6. Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites.

    Science.gov (United States)

    Medcalf, Sharon; Bilek, Laura; Hartman, Teresa; Iwen, Peter C; Leuschen, Patricia; Miller, Hannah; O'Keefe, Anne; Sayles, Harlan; Smith, Philip W

    2015-08-01

    To evaluate the need to revaccinate laboratory workers against smallpox, we assessed regular revaccination at the US Laboratory Response Network's variola testing sites by examining barriers to revaccination and the potential for persistence of immunity. Our data do not provide evidence to suggest prolonging the recommended interval for revaccination.

  7. 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....

  8. Vaccination policy against smallpox, 1835-1914: a comparison of England with Prussia and Imperial Germany.

    Science.gov (United States)

    Hennock, E P

    1998-04-01

    There are three identifiable phases in comparing vaccination policy in England, Prussia and Imperial Germany. (1) Prior to the 1870's the tradition of medical police in Prussia resulted in the vaccination of the population being treated as a State responsibility earlier than in England and provided an appropriate administrative framework. The administrative pressure that could be exerted persuaded the Prussian authorities that legislation to make vaccination compulsory was unnecessary. In contrast, England and Wales lacked both the tradition and administrative structures of a medical police. Legislation (1840, 1853) for free and universal infant vaccination was followed by radical ideological and administrative innovation. (2) From 1875 to 1889 both countries provided free and compulsory vaccination for all. In England this was limited to infants; in Germany including Prussia, it included the re-vaccination of children. (3) After 1889 England and Germany began to diverge more sharply. In England vaccination rates fell and after 1898 conscientious objectors were excused from having to have their children vaccinated. Germany retained compulsory vaccination and rates in the two countries increasingly diverged. England came to rely on the local public health administration for the surveillance and containment of smallpox, including selective vaccination of contacts. Despite these differences smallpox mortality dropped sharply in both countries, although in Germany somewhat earlier. The English reliance on surveillance and containment prefigures that of the WHO in the eradication of smallpox in the Third World. It suggests that the emphasis on the importance of high levels of mass vaccination in the German literature should perhaps be revised.

  9. 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.

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

    Science.gov (United States)

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

    2005-05-10

    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.

  11. Pre-event Smallpox Vaccination for Healthcare Workers Revisited – the Need for a Carefully Screened Multidisciplinary Cadre

    Energy Technology Data Exchange (ETDEWEB)

    Malone, JD D.

    2007-03-01

    Abstract As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia vaccinations were delivered with 1 fatality attributed to vaccination. Among 37,901 U.S. civilian volunteer healthcare workers vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions – 2 were fatal. This older population had a higher rate of adverse events due to age related coronary artery disease. T-cell mediated inflammatory processes, induced by live vaccinia vaccination, may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A smallpox pre-vaccinated multidisciplinary cadre (physician, nurse, infection control practitioner, technician) will supply leadership to deal with fear and uncertainty while limiting spread and initial mortality of smallpox. Stochastic – from the Greek meaning “skillful in aiming” – is currently interpreted as arising from chance and involving probability. This issue’s article “Containing a large bioterrorist smallpox attack: a computer simulation approach” by Longini et al. is a discrete time, stochastic computer simulation model that offers additional planning guidance for a smallpox (variola virus) outbreak (1). Although interpretation of the model’s information may differ, Longini’s article concludes “Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further

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

    Science.gov (United States)

    Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

    2017-01-01

    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 (vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >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. 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).

  14. Demographic and clinical factors associated with response to smallpox vaccine in preimmunized volunteers.

    Directory of Open Access Journals (Sweden)

    Philippe Bossi

    Full Text Available CONTEXT: In March 2003, the French Ministry of Health implemented a program on preparedness and response to a biological attack using smallpox as weapon. This program included the establishment of a preoutbreak national team that could be revaccinated against smallpox. OBJECTIVE: To identify demographic and clinical factors associated with vaccination success defined as the presence of a pustule at the inoculation site at day 8 (days 7-9, with an undiluted vaccinia virus derived from a Lister strain among preimmunized volunteers. VOLUNTEERS AND METHODS: From March 2003 to November 2006, we have studied prospectively 226 eligible volunteers. Demographic data were recorded for each volunteer (age, sex, number of previously smallpox vaccinations and date of the last vaccination. Smallpox vaccine adverse reactions were diagnosed on the basis of clinical examination performed at days 0, 7, 14, 21 and 28 after revaccination. RESULTS: A total of 226 volunteers (sex ratio H/F = 2.7 were revaccinated. Median age was 45 years (range: 27-63 yrs. All volunteers completed follow-up. Median number of vaccinations before revaccination was 2 (range: 1-8. The median delay between time of the study and the last vaccination was 29 years (range; 18-60 yrs. Sixty-one volunteers (27% experienced one (n = 40 or more (n = 21 minor side effects during the 2-14 days after revaccination. Successful vaccination was noted in 216/226 volunteers (95.6% at day 8 and the median of the pustule diameter was 5 mm (range: 1-20 mm. Size of the pustule at day 8 was correlated with age (p = 0.03 and with the presence of axillary adenopathy after revaccination (p = 0.007. Sex, number of prior vaccinations, delay between the last vaccination and revaccination, and local or systemic side effects with the exception of axillary adenopathy, were not correlated with the size of the pustule at day 8. CONCLUSIONS: Previously vaccinated volunteers can be successfully revaccinated with the

  15. Policies for Biodefense Revisited: The Prioritized Vaccination Process for Smallpox

    OpenAIRE

    Kress, Moshe

    2005-01-01

    Annals of Operations Research, 148, pp 5-23 Handling bioierror events that involve contagious agents is a major concern in the war against terror, and is a cause for debate among policymakers about the best response policy. At the core of this debate stands the question which of the post-event policies to adopt: mass vaccination--where maximum vaccination capacity is utilized to uniformly inoculate the entire population, or trace (also called ring or targeted) vaccination--where mass vacc...

  16. Molecular Smallpox Vaccine Delivered by Alphavirus Replicons Elicits Protective Immunity in Mice and Non-human Primates

    Science.gov (United States)

    Hooper, Jay W.; Ferro, Anthony M.; Golden, Joseph W.; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F.; Kamrud, Kurt I.

    2009-01-01

    Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine. PMID:19833247

  17. Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.

    Science.gov (United States)

    Hooper, Jay W; Ferro, Anthony M; Golden, Joseph W; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F; Kamrud, Kurt I

    2009-12-11

    Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 1970s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRPs) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 x 10(6)pfu of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine.

  18. Reflections on New York City's 1947 Smallpox Vaccination Program and Its 1976 Swine Influenza Immunization Program.

    Science.gov (United States)

    Imperato, Pascal James

    2015-06-01

    In 1947, a smallpox outbreak occurred in New York City with a total of twelve cases and two deaths. In order to contain this outbreak, the New York City Department of Health launched a mass immunization campaign that over a period of some 60 days vaccinated 6.35 million people. This article examines in detail the epidemiology of this outbreak and the measures employed to contain it. In 1976, a swine influenza strain was isolated among a few recruits at a US Army training camp at Fort Dix, New Jersey. It was concluded at the time that this virus possibly represented a re-appearance of the 1918 influenza pandemic influenza strain. As a result, a mass national immunization program was launched by the federal government. From its inception, the program encountered a myriad of challenges ranging from doubts that it was even necessary to the development of Guillain-Barré paralysis among some vaccine recipients. This paper examines the planning for and implementation of the swine flu immunization program in New York City. It also compares it to the smallpox vaccination program of 1947. Despite equivalent financial and personnel resources, leadership and organizational skills, the 1976 program only immunized approximately a tenth of the number of New York City residents vaccinated in 1947. The reasons for these marked differences in outcomes are discussed in detail.

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

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Sørup, Signe

    2016-01-01

    BACKGROUND: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vacc......BACKGROUND: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested...... that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population. METHODS: In this case-cohort study, we followed 47 622...... schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes. RESULTS: A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow...

  20. Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed.

    Science.gov (United States)

    Conlin, Ava Marie S; Bukowinski, Anna T; Gumbs, Gia R

    2015-08-26

    The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy.

  1. 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...

  2. Taking advantage of the positive side-effects of smallpox vaccination.

    Science.gov (United States)

    Mayr, A

    2004-06-01

    From the introduction of smallpox vaccination approximately 200 years ago right up to its discontinuation (1980), reports by physicians and scientists about positive side-effects such as healing of chronic skin rashes, reduced susceptibility to various infectious diseases, e.g. measles, scarlet fever and whooping cough, and even the prophylactic use of the vaccination, e.g. against syphilis, were published again and again. Comparison with the period after cessation of vaccination confirms the experiences of the above vaccinators. As early as 1956, targeted research on these observations led to evidence of the 'ring-zone phenomenon', i.e. the production of soluble antiviral substances in infected chicken embryos and cell cultures. With the help of modern immunological and bioengineering methods, it was later possible to demonstrate that these effects are based on the activation of lymphoreticular cells and the regulatory effect of certain cytokines within the context of the non-specific immune system. These findings led to the development of paramunization with paraspecific vaccines from highly attenuated animal pox viruses. During attenuation, deletions in the virus DNA occur. Attenuated animal pox strains are therefore suited for the production of vector vaccines. The fact that these vector vaccines demonstrate an especially high level of paraspecific efficacy and lack harmful effects is likewise the result of the attenuated animal pox viruses. Optimum regulation of the entire immune system leads to increased paramunity already in the first few days after vaccination and to enhanced antigen recognition and thus accelerated commencement of specific immunity.

  3. Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population.

    Directory of Open Access Journals (Sweden)

    Eva-Maria Zitzmann-Roth

    Full Text Available Conventional smallpox vaccines based on replicating vaccinia virus (VV strains (e.g. Lister Elstree, NYCBOH are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication. A new smallpox vaccine candidate based on a non-replicating Modified Vaccinia Ankara (MVA poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial.Cardiac safety of one and two doses of MVA compared to placebo was assessed in 745 healthy subjects. Vaccinia-naïve subjects received either one dose of MVA and one dose of placebo, two doses of MVA, or two doses of placebo by subcutaneous injection four weeks apart; vaccinia-experienced subjects received a single dose of MVA. Solicited and unsolicited adverse events (AE and cardiac safety parameters (recorded as Adverse Events of Special Interest, AESI were monitored after each injection.A total of 5 possibly related AESI (3 cases of palpitations, 2 of tachycardia were reported during the study. No case of myo- or pericarditis occurred. One possibly related serious AE (SAE was reported during the 6-month follow-up period (sarcoidosis. The most frequently observed AEs were injection site reactions.Vaccination with MVA was safe and well tolerated and did not increase the risk for development of myo-/pericarditis.ClinicalTrials.gov NCT00316524.

  4. Large-scale use of freeze-dried smallpox vaccine prepared in primary cultures of rabbit kidney cells

    Science.gov (United States)

    Hekker, A. C.; Bos, J. M.; Rai, N. Kumara; Keja, J.; Cuboni, G.; Emmet, B.; Djalins, J.

    1976-01-01

    A lyophilized smallpox vaccine made from infected monolayer cultures of primary rabbit kidney cells was used together with a calf lymph vaccine in a field trial in Lombok, Indonesia, in 1973. About 60 000 children below 15 years of age were vaccinated: some 50 000 with the tissue culture vaccine and about 10 000 with calf lymph vaccine. Similar results were obtained with both vaccines in primary vaccinees and in revaccinees as regards the take rate, pock reactions, and serious secondary reactions. PMID:1088108

  5. US military service members vaccinated against smallpox in 2003 and 2004 experience a slightly higher risk of hospitalization postvaccination.

    Science.gov (United States)

    Jacobson, Isabel G; Smith, Tyler C; Smith, Besa; Wells, Timothy S; Reed, Robert J; Ryan, Margaret A K

    2008-07-29

    This study explores adverse events severe enough to warrant hospitalization that may have been associated with receiving the smallpox vaccine in conjunction with military service. Cox proportional hazards modeling was used to identify the risk of hospitalization among US active-duty military personnel during a 1-year period following receipt of the smallpox vaccine. The reference group consisted of active-duty military personnel who also received the smallpox vaccine after the conclusion of their health care observation period, allowing for comparison to a temporally and demographically similar population. The risk of hospitalization was slightly elevated among the postvaccine group for any-cause hospitalization and for hospitalization in several broad diagnostic categories. Hospitalizations for asthma, autoimmune diseases, and myopericarditis, were more likely in the postvaccine group. The increased risk of hospitalization for varied outcomes does not necessarily imply a cause-effect relationship, but it does offer areas for more focused study, using longitudinal data to explore the long-term impact of smallpox vaccination on the health of young adults.

  6. 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....

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. [The journey of the vaccine against smallpox: one expedition, two oceans, three continents, and thousands of children].

    Science.gov (United States)

    Tuells, José; Duro-Torrijos, José Luis

    2015-01-01

    Spain encouraged, during the Bourbon dynasty, the formation of scientific expeditions, among which was the Royal Philanthropic Vaccine Expedition, an example of biopolitics applied by the state in order to protect health. The expedition went all over the world, using children as a reservoir to transport the vaccine fluid. Francisco Xavier Balmis established a human chain that arm-to-arm materialized the success of the mission. The characteristics and difficulties which children had to pass through and their contribution to the spread of the smallpox vaccine are analyzed.

  10. 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 individuals

  11. Adverse events post smallpox-vaccination: insights from tail scarification infection in mice with Vaccinia virus.

    Directory of Open Access Journals (Sweden)

    Bruno E F Mota

    Full Text Available 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

  12. Safety and immunogenicity of IMVAMUNE® smallpox vaccine using different strategies for a post event scenario.

    Science.gov (United States)

    Frey, Sharon E; Winokur, Patricia L; Salata, Robert A; El-Kamary, Samer S; Turley, Christine B; Walter, Emmanuel B; Hay, Christine Mhorag; Newman, Frances K; Hill, Heather R; Zhang, Ying; Chaplin, Paul; Tary-Lehmann, Magdalena; Belshe, Robert B

    2013-06-24

    Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE(®) (modified vaccinia Ankara vaccine against smallpox) was compared to the currently recommended 0- and 28-day schedule for non-inferiority by evaluating the magnitude and kinetics of the immune responses. Subjects were assigned to receive IMVAMUNE or placebo administered subcutaneously on Days 0 and 7, Days 0 and 28, or Day 0. Blood was collected for antibody and cell-mediated immune assays. Subjects were followed for safety for 12 months after last vaccination. The primary endpoint of this study was the geometric mean antibody titers (GMT) at 14 days post last vaccination. Of 208 subjects enrolled, 191 received vaccine (Group: 0+7, Group: 0+28 and Group: 0) and 17 received placebo. Moderate/severe systemic reactogenicity after any vaccination were reported by 31.1%, 25.4%, and 28.6% of the subjects for Group: 0+7, Group: 0+28, and Group: 0, respectively (Chi-square test, P=0.77). Based on BN's Plaque Reduction Assay GMTs, Group: 0+7 was non-inferior to Group: 0+28 at Day 4, 180, and 365 after the second vaccination. On Day 14, Group: 0+7 and Group: 0+28 GMT were 10.8 (CI: 9.0, 12.9) and 30.2 (CI: 22.1, 41.1), respectively. Based on BN's Enzyme-linked immunosorbent assay, the proportion of subjects with positive titers for Group: 0+28 was significantly greater than that for Group: 0+7 after second vaccination at Days 4 and 180. By Day 14 after the second dose, the IFN-γ enzyme-linked immunosorbent spot (ELISPOT) responses were similar for Group: 0+28 and Group: 0+7. Overall, a standard dose of IMVAMUNE (0.5 mL of 1 x 10(8) TCID/mL) administered subcutaneously was safe and well tolerated. A second dose of IMVAMUNE at Day 28 compared to Day 7 provided greater antibody responses and the maximal number of responders. By Day 14 after the second dose, IFN-γ ELISPOT responses were similar for Group: 0+28 and Group: 0

  13. Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults.

    Science.gov (United States)

    Kennedy, Jeffrey S; Gurwith, Marc; Dekker, Cornelia L; Frey, Sharon E; Edwards, Kathryn M; Kenner, Julie; Lock, Michael; Empig, Cyril; Morikawa, Shigeru; Saijo, Masayuki; Yokote, Hiroyuki; Karem, Kevin; Damon, Inger; Perlroth, Mark; Greenberg, Richard N

    2011-11-01

    LC16m8 is an attenuated cell culture-adapted Lister vaccinia smallpox vaccine missing the B5R protein and licensed for use in Japan. We conducted a phase I/II clinical trial that compared the safety and immunogenicity of LC16m8 with Dryvax in vaccinia-naive participants. Adverse events were assessed, as were electrocardiography and laboratory testing for cardiotoxicity and viral culturing of the vaccination sites. Neutralization titers to vaccinia, monkeypox, and variola major were assessed and cell-mediated immune responses were measured by interferon (IFN)-γ enzyme-linked immunosorbent spot and lymphoproliferation assays. Local and systemic reactions after vaccination with LC16m8 were similar to those reported after Dryvax. No clinically significant abnormalities consistent with cardiac toxicity were seen for either vaccine. Both vaccines achieved antivaccinia, antivariola, and antimonkeypox neutralizing antibody titers >1:40, although the mean plaque reduction neutralization titer of LC16m8 at day 30 after vaccination was significantly lower than Dryvax for anti-NYCBH vaccinia (P smallpox. Clinical Trials Registration. NCT00103584.

  14. [The historical development of immunization in Germany. From compulsory smallpox vaccination to a National Action Plan on Immunization].

    Science.gov (United States)

    Klein, S; Schöneberg, I; Krause, G

    2012-11-01

    In the German Reich, smallpox vaccinations were organized by the state. A mandatory vaccination throughout the empire was introduced in 1874, which was continued in the Federal Republic of Germany (FRG) and the German Democratic Republic (GDR) until 1982/1983. From 1935, health departments were responsible for vaccinations. In the GDR, immunization was tightly organized: The state made great efforts to achieve high vaccination rates. Responsibilities were clearly defined at all levels and for all ages. While vaccination was initially mandatory only at the regional level, the legally mandated immunization schedule later contained compulsory vaccinations, e.g., against measles. In the beginning there were mandatory vaccinations in the FRG at the Länder level. Since 1961, the Federal Epidemics Act has impeded obligatory vaccinations. Instead, voluntary vaccinations based on recommendations were stressed. Since the 1980s, vaccinations have been shifted from the public health service sector to office-based physicians. Today, public health authorities offer mainly supplementary vaccinations. In 2007, protective immunizations were introduced as compulsory benefits of the statutory health insurance (SHI). Recently, the German federal states developed a National Vaccination Plan to support immunization strategies.

  15. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC).

    Science.gov (United States)

    Wharton, Melinda; Strikas, Raymond A; Harpaz, Rafael; Rotz, Lisa D; Schwartz, Benjamin; Casey, Christine G; Pearson, Michele L; Anderson, Larry J

    2003-04-01

    This report supplements the 2001 statement by the Advisory Committee on Immunization Practices (ACIP) (CDC. Vaccinia [smallpox] vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP], 2001. MMWR 2001;50[No. RR-10]:1-25). This supplemental report provides recommendations for using smallpox vaccine in the pre-event vaccination program in the United States. To facilitate preparedness and response, smallpox vaccination is recommended for persons designated by public health authorities to conduct investigation and follow-up of initial smallpox cases that might necessitate direct patient contact. ACIP recommends that each state and territory establish and maintain > or = 1 smallpox response team. ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend that each acute-care hospital identify health-care workers who can be vaccinated and trained to provide direct medical care for the first smallpox patients requiring hospital admission and to evaluate and manage patients who are suspected as having smallpox. When feasible, the first-stage vaccination program should include previously vaccinated health-care personnel to decrease the potential for adverse events. Additionally persons administering smallpox vaccine in this pre-event vaccination program should be vaccinated. Smallpox vaccine is administered by using the multiple-puncture technique with a bifurcated needle, packaged with the vaccine and diluent. According to the product labeling, 2-3 punctures are recommended for primary vaccination and 15 punctures for revaccination. A trace of blood should appear at the vaccination site after 15-20 seconds; if no trace of blood is visible, an additional 3 insertions should be made by using the same bifurcated needle without reinserting the needle into the vaccine vial. If no evidence of vaccine take is apparent after 7 days, the person can be vaccinated again. Optimal infection-control practices and appropriate

  16. [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).

  17. Mucosal Immunization Induces a Higher Level of Lasting Neutralizing Antibody Response in Mice by a Replication-Competent Smallpox Vaccine: Vaccinia Tiantan Strain

    Directory of Open Access Journals (Sweden)

    Bin Lu

    2011-01-01

    Full Text Available The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain for inducing neutralizing antibodies (Nabs through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m., intranasal (i.n., oral (i.o., and subcutaneous (s.c. inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.

  18. Mucosal immunization induces a higher level of lasting neutralizing antibody response in mice by a replication-competent smallpox vaccine: vaccinia Tiantan strain.

    Science.gov (United States)

    Lu, Bin; Yu, Wenbo; Huang, Xiaoxing; Wang, Haibo; Liu, Li; Chen, Zhiwei

    2011-01-01

    The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain) for inducing neutralizing antibodies (Nabs) through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m.), intranasal (i.n.), oral (i.o.), and subcutaneous (s.c.) inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.

  19. 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

    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...... Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36-1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43-1.15) in Denmark. We combined the results from both settings in a meta...

  20. 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

    conditions 18 0.0 7 0.0 1.92 0.79, 4.69 280 Iron deficiency anemias 16 0.0 7 0.0 1.52 0.60, 3.84 288 Diseases of white blood cells 11 0.0 6 0.0 1.43...public release: distribution is unlimited. Naval Health Research Center 140 Sylvester Road San Diego, California 92106 This article appeared...Naval Health Research Center US Military Service Members Vaccinated Against Smallpox in 2003 and 2004 Experience a Slightly Higher Risk of

  1. 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.

  2. [Use of antibiotics in the treatment of ulceronecrotic tonsillitis due to vaccination by tabletted smallpox vaccine].

    Science.gov (United States)

    Bondarev, V P; Borisevich, I V; Mel'nikov, S A; Kaskov, A V; Shagarov, E E; Chernikova, N K; Dorokhina, T V; Rylov, A V; Bondareva, T A; Terent'ev, A I

    2010-01-01

    Clinical trials of tabletted pox vaccine revealed development of tonsillitis as a postvaccinal reaction in some volunteers: ulceronecrotic lesions in the tonsils, lymphadenitis, hyperthermia and asthenia. The main cause of the local inflammatory reactions was activation of the host opportunistic microflora including hemolytic streptococci and Staphylococcus aureus. For the treatment of the infectious complications systemic antimicrobials, such as benzylpenicillin, amoxicillin, ampicillin, cefazolin and fluoroquinolones (ciprofloxacin) in combination with the symptomatic therapy were used. The treatment course of 9 days provided complete elimination of the postvaccinal reactions, the specific antibody generation being not affected.

  3. Genome Sequence of Vaccinia virus Strain Lister-Butantan, a Lister Vaccine Variant Used during a Smallpox Eradication Campaign in Brazil

    Science.gov (United States)

    Assis, Felipe; Trindade, Giliane; Drumond, Betânia; Frace, Mike; Sammons, Scott; Emerson, Ginny; Li, Yu; Carroll, Darin; Batra, Dhwani; Kroon, Erna

    2016-01-01

    Here, we report the 187.8-kb genome sequence of Vaccinia virus Lister-Butantan, which was used in Brazil during the WHO smallpox eradication campaign. Its genome showed an average similarity of 98.18% with the original Lister isolate, highlighting the low divergence among related Vaccinia virus vaccine strains, even after several passages in animals and cell culture. PMID:27340056

  4. Medical Surveillance Monthly Report (MSMR). Volume 21, Number 8, August 2014

    Science.gov (United States)

    2014-08-01

    Greenberg M. Complications of vaccination against smallpox. Am J Dis Child . 1948;76:492– 502. 2. Leake JP. Question and answers on smallpox vaccination ...documented.12,13 Th e only smallpox vaccine currently available for use in the U.S. is ACAM2000®, which was approved by the Food and Drug...Force train- ing installation, select technical training students receive the smallpox vaccination in accordance with current Department of Defense

  5. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination.

    Directory of Open Access Journals (Sweden)

    Renata J M Engler

    Full Text Available Although myocarditis/pericarditis (MP has been identified as an adverse event following smallpox vaccine (SPX, the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined.The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization.New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT elevations following SPX (above individual baseline values were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV.New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR 4.0, 95% CI: 1.7-9.3. Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558. Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile from baseline (pre-SPX during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group.Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further

  6. Smallpox vaccination in the early 19th century using live carriers: the travels of Francisco Xavier de Balmis.

    Science.gov (United States)

    Aldrete, J Antonio

    2004-04-01

    Realizing that the Spanish colonies were being devastated by epidemics of smallpox resulting in thousands of deaths, Charles IV, King of Spain, sent one of his court's physicians to apply the recently discovered vaccine. Without refrigeration, the vaccine was passed from one child to another (boys taken out of orphanages). Francisco Xavier de Balmis and a team that included three assistants, two surgeons, and three nurses sailed from Spain on November 30. 1803. They vaccinated more than 100,000 people from the Caribbean Islands and South, Central, and North America, reaching up to San Antonio, Texas, and then traveled to the Philippines, Macao, Canton, and Santa Elena Island, landing back in Cadiz on September 7, 1806. During his journey, Balmis instructed local physicians on how to prepare, preserve, and apply the vaccine, while collecting rare biologic specimens. On the 200th anniversary of their sailing, recognition is given to this group for conducting what was the first global vaccination campaign that reached Texas and California.

  7. 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.

  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. Smallpox - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Hmong) PDF Minnesota Department of Health Khmer (Khmer) Smallpox Vaccine English វ៉ាក់សាំង smallpox - Khmer (Khmer) PDF ... Centers for Disease Control and Prevention Russian (Русский) Smallpox Vaccine English Вакцина против оспы - Русский (Russian) PDF Immunization ...

  10. Smallpox: a disease of the past? Consideration for midwives.

    Science.gov (United States)

    Constantin, Carolyn M; Martinelli, Angela M; Foster, Stanley O; Bonney, Elizabeth A; Strickland, Ora L

    2003-01-01

    Smallpox infection was often more severe in pregnant women than in non-pregnant women or in men, regardless of vaccination status. Women with smallpox infection during pregnancy have higher rates of abortions, stillbirths, and preterm deliveries than women without the disease. Pregnant women have high incidences of hemorrhagic-type and flat-type smallpox, which are associated with extremely high fatality rates. Although smallpox was eradicated in the late 1970s, current international concern exists regarding the potential use of smallpox virus as an agent for bioterrorism. This manuscript reviews clinical aspects of smallpox, smallpox immunization, and outcomes in pregnant women.

  11. An Attenuated LC16m8 Smallpox Vaccine: Analysis of Full-Genome Sequence and Induction of Immune Protection§

    Science.gov (United States)

    Morikawa, Shigeru; Sakiyama, Tokuki; Hasegawa, Hideki; Saijo, Masayuki; Maeda, Akihiko; Kurane, Ichiro; Maeno, Go; Kimura, Junko; Hirama, Chie; Yoshida, Teruhiko; Asahi-Ozaki, Yasuko; Sata, Tetsutaro; Kurata, Takeshi; Kojima, Asato

    2005-01-01

    The potential threat of smallpox bioterrorism has made urgent the development of lower-virulence vaccinia virus vaccines. An attenuated LC16m8 (m8) vaccine was developed in 1975 from the Lister strain used in the World Health Organization smallpox eradication program but was not used against endemic smallpox. Today, no vaccines can be tested with variola virus for efficacy in humans, and the mechanisms of immune protection against the major intracellular mature virion (IMV) and minor extracellular enveloped virion (EEV) populations of poxviruses are poorly understood. Here, we determined the full-genome sequences of the m8, parental LC16mO (mO), and grandparental Lister (LO) strains and analyzed their evolutionary relationships. Sequence data and PCR analysis indicated that m8 was a progeny of LO and that m8 preserved almost all of the open reading frames of vaccinia virus except for the disrupted EEV envelope gene B5R. In accordance with this genomic background, m8 induced 100% protection against a highly pathogenic vaccinia WR virus in mice by a single vaccination, despite the lack of anti-B5R and anti-EEV antibodies. The immunogenicity and priming efficacy with the m8 vaccine consisting mainly of IMV were as high as those with the intact-EEV parental mO and grandparental LO vaccines. Thus, mice vaccinated with 107 PFU of m8 produced low levels of anti-B5R antibodies after WR challenge, probably because of quick clearance of B5R-expressing WR EEV by strong immunity induced by the vaccination. These results suggest that priming with m8 IMV provides efficient protection despite undetectable levels of immunity against EEV. PMID:16140764

  12. 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 ...

  13. Vaccine Safety

    Science.gov (United States)

    ... Vaccine Safety Shingles (Herpes Zoster) Vaccine Safety Smallpox Vaccine Safety Common Concerns Adjuvants Autism CDC Statement: 2004 Pediatrics Paper on MMR and Autism Fainting (Syncope) Febrile ...

  14. [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.

  15. 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...

  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. 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.…

  18. Proteomic basis of the antibody response to monkeypox virus infection examined in cynomolgus macaques and a comparison to human smallpox vaccination.

    Directory of Open Access Journals (Sweden)

    Sarah Keasey

    Full Text Available Monkeypox is a zoonotic viral disease that occurs primarily in Central and West Africa. A recent outbreak in the United States heightened public health concerns for susceptible human populations. Vaccinating with vaccinia virus to prevent smallpox is also effective for monkeypox due to a high degree of sequence conservation. Yet, the identity of antigens within the monkeypox virus proteome contributing to immune responses has not been described in detail. We compared antibody responses to monkeypox virus infection and human smallpox vaccination by using a protein microarray covering 92-95% (166-192 proteins of representative proteomes from monkeypox viral clades of Central and West Africa, including 92% coverage (250 proteins of the vaccinia virus proteome as a reference orthopox vaccine. All viral gene clones were verified by sequencing and purified recombinant proteins were used to construct the microarray. Serum IgG of cynomolgus macaques that recovered from monkeypox recognized at least 23 separate proteins within the orthopox proteome, while only 14 of these proteins were recognized by IgG from vaccinated humans. There were 12 of 14 antigens detected by sera of human vaccinees that were also recognized by IgG from convalescent macaques. The greatest level of IgG binding for macaques occurred with the structural proteins F13L and A33R, and the membrane scaffold protein D13L. Significant IgM responses directed towards A44R, F13L and A33R of monkeypox virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with pathogenic virus strains, while recovery from infection also involved humoral responses to antigens uniquely recognized within the monkeypox virus proteome.

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

    Science.gov (United States)

    McKinney, Brett A.; Lareau, Caleb; Oberg, Ann L.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Poland, Gregory A.

    2016-01-01

    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. PMID:27513748

  20. Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox.

    Directory of Open Access Journals (Sweden)

    Melanie Kremer

    Full Text Available Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.

  1. Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus.

    Science.gov (United States)

    Flesch, Inge E A; Hollett, Natasha A; Wong, Yik Chun; Quinan, Bárbara Resende; Howard, Debbie; da Fonseca, Flávio G; Tscharke, David C

    2015-09-01

    CD8(+) T cells that recognize virus-derived peptides presented on MHC class I are vital antiviral effectors. Such peptides presented by any given virus vary greatly in immunogenicity, allowing them to be ranked in an immunodominance hierarchy. However, the full range of parameters that determine immunodominance and the underlying mechanisms remain unknown. In this study, we show across a range of vaccinia virus strains, including the current clonal smallpox vaccine, that the ability of a strain to spread systemically correlated with reduced immunodominance. Reduction in immunodominance was observed both in the lymphoid system and at the primary site of infection. Mechanistically, reduced immunodominance was associated with more robust priming and especially priming in the spleen. Finally, we show this is not just a property of vaccine and laboratory strains of virus, because an association between virulence and immunodominance was also observed in isolates from an outbreak of zoonotic vaccinia virus that occurred in Brazil.

  2. Smallpox Vaccine Overview

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  3. Live Virus Smallpox Vaccine

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  4. 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…

  5. 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.

  6. Vacinação, varíola e uma cultura da imunização no Brasil Vaccination, smallpox, and a culture of immunization in Brazil

    Directory of Open Access Journals (Sweden)

    Gilberto Hochman

    2011-02-01

    Full Text Available O objetivo deste artigo é discutir a emergência e o estabelecimento de uma "cultura da imunização" no Brasil contemporâneo a partir da erradicação da varíola. Essa cultura está associada a um longo processo de introdução de vacinas, de campanhas de vacinação e de vacinação em massa empreendidas pelo Estado brasileiro desde o final do século XIX. Particular importância é atribuída à campanha de erradicação da varíola no Brasil (1966-1973. A experiência da vacinação em massa da população contra a varíola é contrastada com episódios de resistência como a "Revolta da Vacina", e considerada como crucial na configuração de novas políticas e novas compreensões sobre o papel da imunização na saúde pública e seu lugar na sociedade brasileira.The aim of this paper is to discuss the emergence and establishment of a "culture of immunization" in the contemporary Brazil from the eradication of smallpox. This culture is associated with a long process of introduction of vaccines, vaccination campaigns and mass vaccination undertaken by the Brazilian government since the late nineteenth century. Particular importance is attributed to the campaign to eradicate smallpox in Brazil (1966-1973. The experience of mass vaccination of the population against smallpox is contrasted with episodes of resistance as the "revolt against the vaccine", and regarded as crucial in shaping new policies and new understandings about the role of immunization in public health and its place in society Brazil.

  7. On the falsifications in history: Juan José Heydeck (n. 1755 and his «amazing» discovery of a vaccine against the smallpox

    Directory of Open Access Journals (Sweden)

    Olagüe de Ros, Guillermo

    2007-06-01

    Full Text Available Juan Jose Heydeck (b. 1755 is a turbid figure that in the last years he is acquiring certain historical relief. His false find of a vaccine has been overvalued, in excess, against the smallpox in goats of Madrid. In this note, which is a response to an article appeared in Asclepio in 2006, this personage is checked from an historical point of view and there is demonstrated the falsehood of his find, fruit of his excessive ambition.

    Juan José Heydeck (n. 1755 es una turbia figura que en los últimos años está adquiriendo cierto relieve historiográfico. Se ha sobrevalorado, en exceso, su falso hallazgo de una vacuna contra la
    viruela en cabras de Madrid. En esta nota, que es respuesta a un artículo aparecido en esta revista en 2006, se revisa historiográficamente a este personaje y se demuestra la falsedad de su hallazgo, fruto de su ambiciosa y desmedida ambición.

  8. Marcados en la piel: vacunación y viruela en Argentina (1870-1910 Marked on the skin: vaccination and smallpox in Argentina (1870-1910

    Directory of Open Access Journals (Sweden)

    Maria Silvia Di Liscia

    2011-02-01

    Full Text Available Este artículo estudia la vacunación antivariólica en Argentina desde 1870, cuando se inician los debates al respecto, hasta la década de 1910, cuando se amplía al resto del país. Se analizan las prácticas de inmunización puestas en marcha con anterioridad a la Ley de vacunación obligatoria, aprobada en 1886 para la Capital y en 1904 para el resto del país. Tal medida fue resistida desde diferentes sectores. Su aprobación dependió de las consecuencias del proceso de modernización y urbanización acelerada, del peso de los higienistas en el escenario político y su extensión dependió de una concepción administrativa diferente, que incorporaba nuevas áreas y sectores al escenario nacional.This paper studies the smallpox vaccination in Argentina since 1870, when these discussions were inittiaded until the 1910s, when they were extended to the rest of the country. We analyze immunization practices implemented prior to the compulsory vaccination law, passed in 1886 for the Capital and in 1904 for the rest of the country. Such a move found resistance from different sectors. Its approval depended on the consequences of modernization and urbanization, the weight of hygienists in the political arena, and its extension depended on a different administrative conception, incorporating new areas and sectors to the national scenario.

  9. Frequently Asked Questions and Answers on Smallpox

    Science.gov (United States)

    ... protect anyone else judged to have a high risk of exposure to smallpox. The vaccine cannot be used in ... only to those persons who have a high risk of coming into contact with the virus which ... health workers and hospital personnel around the world have been trained to ...

  10. Sudden Infant Death Syndrome (SIDS) and Vaccines

    Science.gov (United States)

    ... Vaccine Safety Shingles (Herpes Zoster) Vaccine Safety Smallpox Vaccine Safety Common Concerns Adjuvants Autism CDC Statement: 2004 Pediatrics Paper on MMR and Autism Fainting (Syncope) Febrile ...

  11. 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.

  12. 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

  13. [Smallpox is a dormant volcano].

    Science.gov (United States)

    L'vov, D K; Zverev, V V; Gintsburg, A L; Marennikova, S S; Pal'tsev, M A

    2008-01-01

    The presence of rodent-associated natural foci containing at least 6 of the known 11 viruses belonging to the genus Orthopoxvirus (Poxviridae, Chordopoxvirinae) within the equatorial, tropical, subtropical, temperate, and subarctic climatic zones; the increasing aggravation of the monkey pox epidemic situation in equatorial Africa with an increase in human mortality by an average of 9.8% with a possibility of 2 to 8 passages in 30-70% of patients; the possible persistence of a virus in the human cadavers buried in the permafrost of Eurasia and America; bioterrorism threat due to the unaccounted viral reserves persisting somewhere or somebody; no postvaccinal human immunity since vaccination and vaccine manufacture stopped 30 years ago as recommended by the WHO, make the risk of the deteriorating epidemic situation with disastrous effects greater now and in the foreseeable future than it was 20-30 years ago. Health care academic circles and bodies do not know methods for rapid diagnosis in the field conditions of species-specific identification smallpox virus or preventive (low-reactogenic, effective vaccines, and those accessible for mass production) and therapeutic (nontoxic drugs, those satisfactory for mass production, inexpedient, effective ones when orally used) agents. Basic studies of biodiversity, functional properties of viral DNA and proteins, pathogenesis, and evolution are required. Live smallpox virus should be used at certain and particularly final stages for these studies that are of scientific and applied significance.

  14. 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.

  15. 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.

  16. Smallpox epidemic in a Brazilian community.

    Science.gov (United States)

    de Azeredo Costa, E; Morris, L

    1975-06-01

    The most severe outbreak of smallpox in Brazil in 1969 took place in the municipio of Utinga, Bahia. Of 507 cases, 246 occurred in residents of the urban area of the municipio. This paper describes the findings of the detailed study of the urban area outbreak. An inverse relationship between age and susceptibility was evident; fully 91% of the children less than 5 years of age as well as 75% of the school-age children had no history of smallpox and had never been vaccinated. The overall attack rate was 11% with nearly three-fourths of the cases in children under 15 years of age. Only 4 of the 246 patients had a vaccination scar, and the estimate of vaccine efficacy was 94%. The continued occurrence of cases after the initial vaccination containment measures prompted detailed studies during 2 follow-up visits to the community which demonstrated that 1) transmission of smallpox may continue in a pocket of susceptibles although the overall immune status of a community is high following containment measures, and 2) clinical illness may have been aborted in those affected individuals who were only in their second to fourth day of incubation at the time of vaccination.

  17. 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.

  18. Smallpox: Is the Department of Defense Prepared?

    Science.gov (United States)

    2003-01-01

    medications ( cidofovir , adefovir dipivoxil, cyclic cidofivir, and ribavirin) show in vitro activity against variola virus and are undergoing further testing...further treatment including VIG or cidofovir . Dose Related Effects of Smallpox Vaccine (Frey 2002) provides data from a dilution study of Dryvax...antiviral medications. Thus far, in vitro testing has shown the drug cidofovir to have activity against variola virus and makes it the leading antiviral

  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. Os primórdios da vacina antivariólica em São Paulo: uma história pouco conhecida The beginnings of the smallpox vaccine in São Paulo: a little-known storu

    Directory of Open Access Journals (Sweden)

    Luiz Antonio Teixeira

    2003-01-01

    Full Text Available O artigo discute as práticas de profilaxia contra a varíola no estado de São Paulo, tendo como objeto privilegiado de análise o Instituto Vacinogênico, instituição criada em 1892, no âmbito de uma reforma sanitária que modernizou a saúde pública no estado de São Paulo. Implantado e dirigido até o ano de 1913 pelo reputado cirurgião paulista Arnaldo Vieira de Carvalho, o instituto foi responsável pela disseminação da vacina antivariólica de origem animal no estado, funcionando de forma autônoma até 1918, quando foi anexado ao Instituto Bacteriológico.This discussion of smallpox prevention practices in the state of São Paulo focuses primarily on the Instituto Vacinogênico, created in 1892 as part of a sanitation reform that modernized public health in São Paulo state. Established and headed until 1913 by the renowned São Paulo surgeon Arnaldo Vieira de Carvalho, the institute was responsible for statewide distribution of the smallpox vaccine derived from animals. It operated on its own until 1918, when it was made part of the Instituto Bacteriológico.

  1. Mankind's Magnificent Milestone: Smallpox Eradication.

    Science.gov (United States)

    Small, Parker A., Jr.; Small, Natalie S.

    1996-01-01

    Illustrates the complex interactions between disease, societal attitudes, and technology by looking at the history of smallpox. Describes one of mankind's most magnificent accomplishments--the eradication of smallpox from the earth. (JRH)

  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. Assay of neutralizing antibody against variola virus by the degree of focus reduction on HeLa cell cultures and its application to revaccination with smallpox vaccines of various potencies.

    Science.gov (United States)

    Kitamura, T; Shinjo, N

    1972-01-01

    A method for assaying neutralizing antibody against variola virus was established by focus counting on HeLa cell cultures. The ND(50) titre, i.e., the serum dilution endpoint to give a 50% reduction in the number of foci, was determined with excellent reproducibility.Groups of students 19-20 years of age were revaccinated by the multiple pressure method with serial 10-fold dilutions of a smallpox vaccine and their neutralizing antibody response was assayed by the focus counting assay system and was related to the local skin reactions on the seventh day after inoculation and to the potency of the vaccine administered. There was a significant rise in the antibody level even after inoculation with a vaccine whose potency was as low as 1.3 x 10(5) pock-forming units/ml. In general, the rise in the log antibody level was proportional to the diameter of the reddening, but a significant rise was found among individuals who had no detectable skin reaction. The skin reaction was greater among individuals with a lower initial antibody level when the vaccine administered had a potency lower than 1.3 x 10(6) pock-forming units/ml.

  4. 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

    Science.gov (United States)

    Greenberg, Richard N; Hurley, Yadira; Dinh, Dinh V.; Mraz, Serena; Vera, Javier Gomez; von Bredow, Dorothea; von Krempelhuber, Alfred; Roesch, Siegfried; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Meyer, Thomas Peter; Schmidt, Darja; Nichols, Richard; Young, Philip; Chaplin, Paul

    2015-01-01

    Background 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. Objective This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects. Methods 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. Results 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. Limitations The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%. Conclusion MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD. Trial Registration ClinicalTrials.gov NCT00316602 PMID:26439129

  5. 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.

  6. 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.

  7. 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 vaccination-re

  8. 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 vaccination-re

  9. Side Effects of Smallpox Vaccination

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  10. 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.

    Directory of Open Access Journals (Sweden)

    Richard N Greenberg

    Full Text Available 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

  11. 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; von Krempelhuber, Alfred; Young, Philip; Nichols, Richard; Meyer, Thomas P.; Weigl, Josef; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2016-01-01

    Background 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. Methods 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. Results 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

  12. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960.

    Science.gov (United States)

    Brimnes, Niels

    2011-02-01

    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.

  13. 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.

  14. Smallpox: emergence, global spread, and eradication.

    Science.gov (United States)

    Fenner, F

    1993-01-01

    Speculatively, it is suggested that variola virus, the cause of smallpox, evolved from an orthopoxvirus of animals of the central African rain forests (possibly now represented by Tatera poxvirus), some thousands of years ago, and first became established as a virus specific for human beings in the dense populations of the Nile valley perhaps five thousand years ago. By the end of the first millennium of the Christian era, it had spread to all the densely populated parts of the Eurasian continent and along the Mediterranean fringe of north Africa. It became established in Europe during the times of the Crusades. The great voyages of European colonization carried smallpox to the Americas and to Africa south of the Sahara. Transported across the Atlantic by Europeans and their African slaves, it played a major role in the conquest of Mexico and Peru and the European settlement of north America. Variolation, an effective preventive inoculation, was devised as early as the tenth century. In 1798 this practice was supplanted by Jenner's cowpox vaccine. In 1967, when the disease was still endemic in 31 countries and caused ten to fifteen million cases and about two million deaths annually, the World Health Organization embarked on a programme that was to see the disease eradicated globally just over ten years later, and the world was formally declared to be free of smallpox in May 1980. Smallpox is unique--a specifically human disease that emerged from some animal reservoir, spread to become a worldwide, severe and almost universal affliction, and finally underwent the reverse process to emergence, namely global eradication.

  15. The discontinuation of routine smallpox vaccination in the United States, 1960-1976: an unlikely affirmation of biomedical hegemony A descontinuação da vacinação de rotina contra a varíola nos Estados Unidos, 1960-1976: uma afirmação improvável da hegemonia biomédica

    Directory of Open Access Journals (Sweden)

    Miriam Rich

    2011-02-01

    Full Text Available This article seeks to understand the discursive context of the cessation of routine smallpox vaccination in the United States in the early 1970s. The United States has a long tradition of opposition to compulsory smallpox vaccination, usually expressed in terms of concerns about personal liberties, the extent of state authority, and challenges to the hegemony of orthodox biomedicine. The practice of routine smallpox vaccination continued in the United States until its termination in the 1970s, following a 1971 recommendation against the practice issued by the United States Public Health Service. This history investigates the ways in which opposition to compulsory smallpox vaccination in the 1960s and 70s was articulated and understood by contemporaries through an analysis of the rhetoric used in leading medical journals and popular newspapers. It finds that this ultimately successful movement to end routine smallpox vaccination drew upon the language of biomedical authority rather than political protest.Este artigo procura entender o contexto discursivo da cessação da vacinação de rotina contra varíola nos Estados Unidos no início dos anos 70. Os Estados Unidos têm uma longa tradição na oposição à vacinação compulsória contra a varíola, geralmente expressa em relação ao que se refere à liberdade pessoal, à extensão da autoridade estadual e desafios à hegemonia da biomedicina ortodoxa. A rotina de vacinação contra varíola continuou nos Estados Unidos até a extinção da doença nos anos 70, seguida de uma recomendação em 1971 contra a prática emitida pelo Serviço de Saúde Pública dos Estados Unidos. Essa história investiga as maneiras pelas quais a oposição à vacinação compulsória contra a varíola nos anos 60 e 70 foi articulada e entendida por contemporâneos através da análise da retórica utilizada pelos principais periódicos médicos e jornais populares. Descobriu-se que esse movimento bem

  16. Smallpox and its eradication in the Democratic Republic of Congo: lessons learned.

    Science.gov (United States)

    Muyembe-Tamfum, Jean-Jacques; Mulembakani, Prime; Lekie, René Botee; Szczeniowski, Mark; Ježek, Zdeněk; Doshi, Reena; Hoff, Nicole; Rimoin, Anne W

    2011-12-30

    Smallpox eradication is considered to be one of the most remarkable accomplishments of the 20th century. Lessons learned from the campaign during the 1960s and 1970s in the Democratic Republic of Congo (DRC) can provide important information for the development of other eradication programs including polio. The DRC is the third largest country in Africa; the population suffers from extreme poverty, deteriorating infrastructure and health systems, and long periods of civil strife. Despite these challenges, DRC's smallpox eradication campaign was successful, eradicating smallpox only 41 months after initiation. DRC had been polio free since 2001; however, in 2006, imported cases were identified in the country. Polio transmission has since been re-established and DRC now has the second greatest number of reported polio cases in the world. Challenges which existed during the smallpox campaign in DRC are still present today; additionally, the polio vaccine itself poses unique challenges which include requiring multiple doses to confer immunity. In the fight against polio in DRC, it will be important to draw from the smallpox eradication experience. A number of important themes emerged during the campaign that could be beneficial to eradicating polio and future eradication programs that may follow. During the smallpox campaign, a standard vaccination program was implemented, surveillance was intensified, and there were strong collaborative programs with community involvement. These successful elements of the smallpox campaign should be adapted and applied in DRC in polio eradication programs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. 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.

  18. [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.

  19. 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

  20. Proteomic Basis of the Antibody Response to Monkeypox Virus Infection Examined in Cynomolgus Macaques and a Comparison to Human Smallpox Vaccination

    Science.gov (United States)

    2010-12-30

    from small - pox , was first observed in macaques no earlier than 6 days after initial infection. We first examined the antibody response during the...I, Jezek Z, Ladnyi ID (1988) Human monkeypox and other poxvirus infections of man In: Fenner F, ed. Small - pox and its Eradication. Geneva: World...virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with

  1. Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

    Science.gov (United States)

    Tree, Julia A; Hall, Graham; Rees, Peter; Vipond, Julia; Funnell, Simon G P; Roberts, Allen D

    2016-07-01

    Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

  2. Las vacunaciones antivariólicas en Navarra (España entre septiembre y noviembre de 1801 Smallpox vaccinations in Navarre (Spain between September and November 1801

    Directory of Open Access Journals (Sweden)

    J.J. Viñes

    2004-12-01

    Full Text Available Se da noticia de la localización en el Archivo de D. Gaspar Castellano de Gastón, del documento que atestigua las primeras inoculaciones con linfa vacunal en Errazu, localidad del Valle de Baztán (Navarra, realizadas el 2 de Noviembre de 1801, por el médico de San Juan de Pie de Puerto (Francia Dr. Iribarren Ayzin, desde el brazo de una muchacha francesa de 18 años, conducida personalmente por él, a instancia de D. Josef Juaquín Gastón Alcalde del Valle del Baztán. El nuevo hallazgo sirve de homenaje 200 años después a la primera expedición de Salud Pública entre 1803 y 1806, dirigida por el médico alicantino D. Francisco Xavier Balmis, dando la vuelta al mundo, con el fin de difundir la vacuna entre todas las razas y zonas del mundo conocidas.We communicate the discovery in the Archive of D. Gaspar Castellano de Gastón of a document providing evidence of the first inoculations with lymph vaccine in Errazu, a village in the Baztán Valley (Navarre. These were carried out on November 2nd 1801, by a doctor from San Juan Pie de Puerto (France, Dr. Iribarren Ayzin, from the arm of a French girl aged 18, personally brought by him at the request of D. Josef Juaquín Gastón, Mayor of the Baztán Valley. The new finding serves as homage, 200 hundred years later, to the first Public Health expedition, carried out between 1803 and 1806, which travelled around the world in order to spread the vaccine amongst all the races and areas of the known world. The expedition was led by D. Francisco Xavier Balmis, a doctor from Alicante.

  3. 牛痘疫苗接种家兔炎症皮肤提取物治疗神经病理性痛疗效的系统评价%EFFICACY OF EXTRACT OF INFLAMMATORY RABBIT SKIN WITH VACCINATED SMALLPOX VACCINATION FOR NEUROPATHIC PAIN: A SYSTEMATIC REVIEW

    Institute of Scientific and Technical Information of China (English)

    张彩琳; 席鹏; 李亦梅

    2013-01-01

    Objective:To evaluate the treatment effects of extract of inflammatory rabbit skin vaccinated with smallpox vaccination on neuropathic pain according to current clinical research evidence,and provide the theoretical basis for clinical prognostic evaluation.Methods:Electronic database including PubMed,Medalink,Springerlink,CNKI,Tongfang Data,and Wanfang Data were searched,meanwhile related articles were searched by auxiliary manual retrieval,and the reference lists of enrolled reports and reviews were looked up.The search collected the randomized controlled clinical trials on the treatment of extract of inflammatory rabbit skin vaccinated with smallpox vaccination for neuropathic pain from 1987 to 2011.The quality of included trials was evaluated by the Cochrane Handbook.Valid data were extracted and statistically analyzed with the software RevMan 5.0.Results:Totally 1009 patients in fifteen trials were included.Meta-analysis indicated that,compared to placebo,carbamazepine,methycobal,or pancreatic kininogenase,the treatment effects of extract of inflammatory rabbit skin vaccinated with smallpox vaccination for neuropathic pain were better [OR=2.69,95% CI (1.99,3.65)].There were statistically significant differences in the visual analogue scale at the end of the treatment [OR=-1.94,95% CI (-2.05,-1.84)].There was no statistically significant difference in safety between the control group and the treatment group [OR=0.53,95% CI (0.30,0.96)].Conclusion:Extract of inflammatory rabbit skin vaccinated with smallpox vaccination can effectively relieve the neuropathic pain.%目的:根据目前的临床研究证据评价牛痘疫苗接种家兔炎症皮肤提取物用于治疗神经病理性痛的疗效,为临床预后评估提供理论依据.方法:计算机检索PubMed、Medalink、Springerlink、CNKI、同方、万方等数据库,同时辅助手工检索相关文献,查阅纳入文献的参考文献.检索时间为1987至2011年的文献,收集牛痘疫苗接种

  4. [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.

  5. 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.

  6. Modeling the Effect of Herd Immunity and Contagiousness in Mitigating a Smallpox Outbreak.

    Science.gov (United States)

    Graeden, Ellie; Fielding, Russel; Steinhouse, Kyle E; Rubin, Ilan N

    2015-07-01

    The smallpox antiviral tecovirimat has recently been purchased by the U.S. Strategic National Stockpile. Given significant uncertainty regarding both the contagiousness of smallpox in a contemporary outbreak and the efficiency of a mass vaccination campaign, vaccine prophylaxis alone may be unable to control a smallpox outbreak following a bioterror attack. Here, we present the results of a compartmental epidemiological model that identifies conditions under which tecovirimat is required to curtail the epidemic by exploring how the interaction between contagiousness and prophylaxis coverage of the affected population affects the ability of the public health response to control a large-scale smallpox outbreak. Each parameter value in the model is based on published empirical data. We describe contagiousness parametrically using a novel method of distributing an assumed R-value over the disease course based on the relative rates of daily viral shedding from human and animal studies of cognate orthopoxvirus infections. Our results suggest that vaccination prophylaxis is sufficient to control the outbreak when caused either by a minimally contagious virus or when a very high percentage of the population receives prophylaxis. As vaccination coverage of the affected population decreases below 70%, vaccine prophylaxis alone is progressively less capable of controlling outbreaks, even those caused by a less contagious virus (R0 less than 4). In these scenarios, tecovirimat treatment is required to control the outbreak (total number of cases under an order of magnitude more than the number of initial infections). The first study to determine the relative importance of smallpox prophylaxis and treatment under a range of highly uncertain epidemiological parameters, this work provides public health decision-makers with an evidence-based guide for responding to a large-scale smallpox outbreak.

  7. Smallpox inoculation (variolation) in East Africa with special reference to the practice among the Boran and Gabra of Northern Kenya.

    Science.gov (United States)

    Imperato, Pascal James; Imperato, Gavin H

    2014-12-01

    Smallpox inoculation (variolation) was widely reported in sub-Sahara Africa before, during, and after the colonial era. The infective smallpox materials and techniques used, as well as the anatomical sites for inoculation, varied widely among different ethnic groups. The practice among the Boran and Gabra pastoralists of northern Kenya resembled that which was prevalent in a number of areas of Ethiopia. This is not surprising as the Boran also live in southern Ethiopia, and Gabra herdsmen frequently cross the border into this region. The Boran and Gabra technique for smallpox inoculation consisted of taking infective material from the vesicles or pustules of those with active smallpox, and scraping it into the skin on the dorsum of the lower forearm. Although the intent was to cause a local reaction and at most a mild form of smallpox, severe cases of the disease not infrequently resulted. Also, variolated individuals were capable of infecting others with smallpox, thereby augmenting outbreaks and sustaining them. The limited known reports of smallpox inoculation among the Boran and Gabra are presented in this communication. The expansion of vaccination with effective heat stable vaccines, the development of medical and public health infrastructures, and educational programs all contributed to the eventual disappearance of the practice among the Boran and Gabra.

  8. Vaccination against pox diseases under immunosuppressive conditions.

    Science.gov (United States)

    Mayr, A; Danner, K

    1978-01-01

    Pox diseases, caused either by smallpox virus or zoonotic pox viruses or animals, continue to be of potential danger to a non-vaccinated population. Mass vaccinations will become necessary and will then also be administered to persons with immunological aberrations. The vaccines which are presently used against smallpox cause severe complications in such hosts. In contrast, the attenuated vaccinia virus strain MVA is safe even under the conditions of immunosuppression and is recommended for the production of smallpox vaccines. Because of the special epizootic situations and the numerous immunosuppressive factors present in developing countries, the use of such a safe pox vaccine there is of crucial importance.

  9. 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

  10. [Vaccination against mouse pox].

    Science.gov (United States)

    Mahnel, H

    1985-01-01

    Attenuated MVA-strain of vaccinia virus has been efficient in the control of enzootic mousepox and in prophylactic vaccination. The virus has been used as a live vaccine for prophylactic and emergency vaccinations as well as for sanitation of populations. More than 100 000 vaccinations were carried out safely. Even after suspension of the obligatory vaccination of humans against smallpox the MVA-vaccine can be employed without risk and danger.

  11. Bioluminescent imaging of vaccinia virus infection in immunocompetent and immunodeficient rats as a model for human smallpox

    OpenAIRE

    Qiang Liu; Changfa Fan; Shuya Zhou; Yanan Guo; Qin Zuo; Jian Ma; Susu Liu; Xi Wu; Zexu Peng; Tao Fan; Chaoshe Guo; Yuelei Shen; Weijin Huang; Baowen Li; Zhengming He

    2015-01-01

    Due to the increasing concern of using smallpox virus as biological weapons for terrorist attack, there is renewed interest in studying the pathogenesis of human smallpox and development of new therapies. Animal models are highly demanded for efficacy and safety examination of new vaccines and therapeutic drugs. Here, we demonstrated that both wild type and immunodeficient rats infected with an engineered vaccinia virus carrying Firefly luciferase reporter gene (rTV-Fluc) could recapitulate i...

  12. Vaccines in dermatology

    Directory of Open Access Journals (Sweden)

    Mitali M Shah

    2015-01-01

    Full Text Available A vaccine is a biological preparation that improves immunity to a specific disease. More than two centuries have passed since the first successful vaccine for smallpox was developed. We′ve come a long way since. Today′s vaccines are among the 21 st century′s most successful and cost-effective public health tools for preventing diseases.

  13. 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

  14. Following in the footsteps of smallpox: can we achieve the global eradication of measles?

    Directory of Open Access Journals (Sweden)

    Morgan Oliver WC

    2004-03-01

    Full Text Available Abstract Background Although an effective measles vaccine has been available for almost 40 years, in 2000 there were about 30 million measles infections worldwide and 777,000 measles-related deaths. The history of smallpox suggests that achieving measles eradication depends on several factors; the biological characteristics of the organism; vaccine technology; surveillance and laboratory identification; effective delivery of vaccination programmes and international commitment to eradication. Discussion Like smallpox, measles virus has several biological characteristics that favour eradication. Humans are the only reservoir for the virus, which causes a visible illness and infection leading to life-long immunity. As the measles virus has only one genetic serotype which is relatively stable over time, the same basic vaccine can be used world-wide. Vaccination provides protection against measles infection for at least 15 years, although efficacy may be reduced due to host factors such as nutritional status. Measles vaccination may also confer other non-specific health benefits leading to reduced mortality. Accurate laboratory identification of measles cases enables enhanced surveillance to support elimination programmes. The "catch-up, keep-up, follow-up" vaccination programme implemented in the Americas has shown that measles elimination is possible using existing technologies. On 17th October 2003 the "Cape Town Measles Declaration" by the World Health Organisation and the United Nations Childrens Fund called on governments to intensify efforts to reduce measles mortality by supporting universal vaccination coverage and the development of more effective vaccination. Summary Although more difficult than for smallpox, recent experience in the Americas suggests that measles eradication is technically feasible. Growing international support to deliver these programmes means that measles, like smallpox, may very well become a curiosity of history.

  15. Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge

    Science.gov (United States)

    Jones, Dorothy I.; McGee, Charles E.; Sample, Christopher J.; Sempowski, Gregory D.; Pickup, David J.

    2016-01-01

    Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 100% protection against a lethal intranasal RPXV challenge administered 9 months after vaccination. PMID:27146001

  16. 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

  17. 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…

  18. Smallpox as an actual biothreat: lessons learned from its outbreak in ex-Yugoslavia in 1972.

    Science.gov (United States)

    Ristanovic, Elizabeta; Gligic, Ana; Atanasievska, Sonja; Protic-Djokic, Vesna; Jovanovic, Dragutin; Radunovic, Miodrag

    2016-01-01

    Variola (smallpox) virus is classified as class A of potential biological weapons, due to its microbiological, genetic, antigenic and epidemiological characteristics. The potential danger is more real because vaccination against smallpox has stopped since disease eradication in 1979. That is why we want to share our unique, rich experience and acquired knowledge in the fight against this highly contagious and deadly disease during the smallpox outbreak in ex-Yugoslavia in 1972. It was the largest postwar outbreak in Europe when there were officially registered 175 ill patients, 35 of them with lethal outcome. This outbreak was specific by the time of its occurrence, the affected territory, dimensions and some epidemiological characteristics, but also by the well-organized, synchronized and efficient reaction of the competent state services in the fight against it.

  19. Potential virulence determinants in terminal regions of variola smallpox virus genome.

    Science.gov (United States)

    Massung, R F; Esposito, J J; Liu, L I; Qi, J; Utterback, T R; Knight, J C; Aubin, L; Yuran, T E; Parsons, J M; Loparev, V N

    Smallpox eradication culminated the most successful antimicrobial campaign in medical history. To characterize further the linear double-stranded DNA genome of the aetiological agent of smallpox, we have determined the entire nucleotide sequence of the highly virulent variola major virus, strain Bangladesh-1975 (VAR-BSH; 186,102 base pairs, 33.7% G + C; Genbank accession number, L22579). Here we highlight features of the molecule and focus on a few of the 187 putative proteins that probably contribute to pathogenicity and virus host-range properties. One hundred and fifty proteins were markedly similar to those of vaccinia virus (smallpox vaccine), for which a complete sequence has been reported for strain Copenhagen (VAC-CPN; 191,636 base pairs, 33.3% G + C). The remaining 37 proteins reflected variola-specific sequences or open reading frame divergences for variant proteins, which are often truncated or elongated compared with their vaccinia counterparts.

  20. 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

  1. 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.

  2. Vaccinia virus induces rapid necrosis in keratinocytes by a STAT3-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Yong He

    Full Text Available Humans with a dominant negative mutation in STAT3 are susceptible to severe skin infections, suggesting an essential role for STAT3 signaling in defense against cutaneous pathogens.To focus on innate antiviral defenses in keratinocytes, we used a standard model of cutaneous infection of severe combined immunodeficient mice with the current smallpox vaccine, ACAM-2000. In parallel, early events post-infection with the smallpox vaccine ACAM-2000 were investigated in cultured keratinocytes of human and mouse origin.Mice treated topically with a STAT3 inhibitor (Stattic developed larger vaccinia lesions with higher virus titers and died more rapidly than untreated controls. Cultured human and murine keratinocytes infected with ACAM-2000 underwent rapid necrosis, but when treated with Stattic or with inhibitors of RIP1 kinase or caspase-1, they survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release. Treatment with inhibitors of RIP1 kinase and STAT3, but not caspase-1, also reduced the inflammatory response of keratinocytes to TLR ligands. Vaccinia growth properties in Vero cells, which are known to be defective in some antiviral responses, were unaffected by inhibition of RIP1K, caspase-1, or STAT3.Our findings indicate that keratinocytes suppress the replication and spread of vaccinia virus by undergoing rapid programmed cell death, in a process requiring STAT3. These data offer a new framework for understanding susceptibility to skin infection in patients with STAT3 mutations. Interventions which promote prompt necroptosis/pyroptosis of infected keratinocytes may reduce risks associated with vaccination with live vaccinia virus.

  3. 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.

  4. Smallpox

    Science.gov (United States)

    ... of Award Clinical Terms of Award Restriction for China Clinical Terms Guidance Compliance Sample Letter Inclusion Codes ... Division of AIDS Division of Allergy, Immunology, and Transplantation Division of Microbiology and Infectious Diseases Division of ...

  5. [From dreaded epidemic to rare disease - smallpox in Sweden 1750-1900].

    Science.gov (United States)

    Sköld, P

    1994-01-01

    Smallpox contributed to the death of 300,000 people in Sweden between 1750 and 1800. It was one of the most feared diseases of the time. Most victims were children under the age of 10 years. It is estimated that one out of every ten children died from smallpox. The mortality rate was between 10% and 20% but those who survived faced severe complications. Most common were the disfiguring pockmarks among those previously infected. It turned out that women who had contracted smallpox married much later in life than the healthy. Also, both female and male fertility was lowered by smallpox infection. By the mid 1750s inoculation was introduced in Sweden. This was a preventive method where a mild infection was given by putting smallpox matter into an incision in the skin. Success was restricted to the wealthy, even if the doctors tried to reach the common people. The main reasons were lack of confidence for doctors, medical and epidemiological risks, costs and an ineffective organization. In 1801 Eberhard Zacharias Munch of Rosenschöld performed the first vaccination with cowpox matter in Sweden. In a few years an extensive practise was stabilized, which made the Swedish population one of the best vaccinated in the world. Moreover, a unique registration was compiled which, together with the parish records, makes the country one of the best documented. The main reasons behind the success was previous experiences of inoculation, international influences, abolition of the physicians monopoly, an effective organization, better opportunities for financing and rewards, and the compulsory law of 1816.

  6. [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.

  7. 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.

  8. 17(th) 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.

  9. Public health and bioterrorism: renewed threat of anthrax and smallpox.

    Science.gov (United States)

    Wallin, Arūne; Luksiene, Zivile; Zagminas, Kestutis; Surkiene, Gene

    2007-01-01

    Bioterrorism is one of the main public health categorical domains. According to sociological analytics, in postmodern society terrorism is one of the real threats of the 21st century. While rare, the use of biological weapons has a long history. Recently, anthrax has been evaluated as one of the most dangerous biological weapons. Naturally occurring anthrax in humans is a disease acquired from contact with anthrax-infected animals or anthrax-contaminated animal products. Usually anthrax infection occurs in humans by three major routes: inhalational, cutaneous, and gastrointestinal. Inhalational anthrax is expected to account for most serious morbidity and most mortality. The clinical presentation of inhalation anthrax has been described as a two-stage illness. Many factors contribute to the pathogenesis of Bacillus anthracis. Antibiotics, anthrax globulin, corticosteroids, mechanical ventilation, vaccine are possible tools of therapy. Smallpox existed in two forms: variola major, which accounted for most morbidity and mortality, and a milder form, variola minor. Smallpox spreads from person to person primarily by droplet nuclei or aerosols expelled from the oropharynx of infected persons and by direct contact. In the event of limited outbreak with few cases, patients should be admitted to the hospital and confined to rooms that are under negative pressure and equipped with high-efficiency particulate air filtration. In larger outbreaks, home isolation and care should be the objective for most patients. Progress in detection, suitable vaccines, postexposure prophylaxis, infection control, and decontamination might be serious tools in fight against the most powerful biological weapon. To assure that the public health and healthcare system can respond to emergencies, the government should direct resources to strengthen the emergency-response system, create medication stockpiles, and improve the public health infrastructure.

  10. 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.

  11. A brief history of vaccines & vaccination in India

    Science.gov (United States)

    Lahariya, Chandrakant

    2014-01-01

    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 19th 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. PMID:24927336

  12. A brief history of vaccines & vaccination in India

    Directory of Open Access Journals (Sweden)

    Chandrakant Lahariya

    2014-01-01

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

  13. 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

  14. 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.

  15. [Treatment and remedies against smallpox outbreaks in Ferrara in the late nineteenth century].

    Science.gov (United States)

    Vicentini, Chiara Beatrice; Manfredini, Stefano; Altieri, Lorenzo; Lupi, Silvia; Guidi, Enrica; Contini, Carlo

    2013-09-01

    Health interventions against smallpox during the two epidemics in the second half of the 19th century are outlined. The 1871 hospital health report and the medical report on smallpox patients treated at the hospital and poorhouse of Ferrara between January 1891 and January 1892, drawn up by Alessandro Bennati, provide both interesting data and insights into the treatments and remedies of the time. The treatment of this illness was - and indeed could be - nothing other than symptomatic, there being no real means to halt the spread of the disease. Rather, other remedies were found by alleviating pain and regaining energy during the various stages of the disease. A close relationship between vaccination and the incidence and gravity of the illness is underlined. When the practice of vaccination started to be widely employed at the end of the century, there were almost no cases of death due to smallpox. The pharmacopoeias of the time, Antonio Campana's Farmacopea ferrarese in particular, proved an essential guide in the analysis of each document.

  16. Vaccine safety--vaccine benefits: science and the public's perception.

    Science.gov (United States)

    Wilson, C B; Marcuse, E K

    2001-11-01

    The development of cowpox vaccination by Jenner led to the development of immunology as a scientific discipline. The subsequent eradication of smallpox and the remarkable effects of other vaccines are among the most important contributions of biomedical science to human health. Today, the need for new vaccines has never been greater. However, in developed countries, the public's fear of vaccine-preventable diseases has waned, and awareness of potential adverse effects has increased, which is threatening vaccine acceptance. To further the control of disease by vaccination, we must develop safe and effective new vaccines to combat infectious diseases, and address the public's concerns.

  17. Bioluminescent imaging of vaccinia virus infection in immunocompetent and immunodeficient rats as a model for human smallpox

    Science.gov (United States)

    Liu, Qiang; Fan, Changfa; Zhou, Shuya; Guo, Yanan; Zuo, Qin; Ma, Jian; Liu, Susu; Wu, Xi; Peng, Zexu; Fan, Tao; Guo, Chaoshe; Shen, Yuelei; Huang, Weijin; Li, Baowen; He, Zhengming; Wang, Youchun

    2015-01-01

    Due to the increasing concern of using smallpox virus as biological weapons for terrorist attack, there is renewed interest in studying the pathogenesis of human smallpox and development of new therapies. Animal models are highly demanded for efficacy and safety examination of new vaccines and therapeutic drugs. Here, we demonstrated that both wild type and immunodeficient rats infected with an engineered vaccinia virus carrying Firefly luciferase reporter gene (rTV-Fluc) could recapitulate infectious and clinical features of human smallpox. Vaccinia viral infection in wild type Sprague-Dawley (SD) rats displayed a diffusible pattern in various organs, including liver, head and limbs. The intensity of bioluminescence generated from rTV-Fluc correlated well with viral loads in tissues. Moreover, neutralizing antibodies had a protective effect against virus reinfection. The recombination activating gene 2 (Rag2) knockout rats generated by transcription activator-like effector nucleases (TALENs) technology were further used to examine the infectivity of the rTV-Fluc in immunodeficient populations. Here we demonstrated that Rag2-/- rats were more susceptible to rTV-Fluc than SD rats with a slower virus clearance rate. Therefore, the rTV-Fluc/SD rats and rTV-Fluc/Rag2-/- rats are suitable visualization models, which recapitulate wild type or immunodeficient populations respectively, for testing human smallpox vaccine and antiviral drugs. PMID:26235050

  18. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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

    2017-08-24

    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

  1. Parallel simulation of smallpox spreading in large populations based on social contact networks%基于社会接触网络的大规模人群天花传播并行仿真

    Institute of Scientific and Technical Information of China (English)

    许晴; 祖正虎; 张文斗; 徐致靖; 黄培堂; 郑涛

    2012-01-01

    天花生物恐怖是世界各国面临的重大潜在威胁.本文利用并行仿真的技术手段,研究天花在大规模城市人群中的传播规律并对环形接种和大规模疫苗接种这两种主要的天花疫苗接种策略进行有效性分析,结果表明环形接种措施能够有效控制天花疫情的扩散,在天花疫苗储备不足的情况下可以优先考虑采用该措施.%Smallpox bioterrorism is a potentially significant threat to the world. This paper used the parallel simulation method to study the spread of smallpox in large urban populations and analyzed the effectiveness of two main smallpox vaccination strategies,which are ring vaccination and mass vaccination. The result showed that ring vaccination strategy can effectively control smallpox epidemic and should be given priority in case of shortage of smallpox vaccine reserves.

  2. 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.

  3. "A wild and wondrous ride": CDC field epidemiologists in the east Pakistan smallpox and cholera epidemics of 1958.

    Science.gov (United States)

    Greenough, Paul

    2011-02-01

    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.

  4. 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

  5. 天花病名流变考%A Study on the Chinese Name of Smallpox

    Institute of Scientific and Technical Information of China (English)

    刘思媛

    2015-01-01

    现知最早记载天花的中医古籍《肘后备急方》中称天花为“虏疮”,后来又出现了“圣疮”“天疮”“豌豆疮”“麸豆疮”“痘疹”等多种称谓。历史上天花病名的繁杂更替,是中医关于天花的理论认识逐渐演变的显著标志。天花病名与中医相关诊断治疗、民间相关社会习俗均有联系。民国时期,“天花”最终替代“痘疹”成为这种病毒性传染病的专有名称,是牛痘接种术传入之后,中医在天花防治中的重要地位被预防接种所取代的结果。%The Zhou hou fang ( Handbook of Formulae) is the earliest known ancient medical book carrying the title of smallpox, called“lu chuan” ( captive sore) .Since then, various names had been ap-plied to this disorder, including “sheng chuang” (holy sore),“tian chuang” (celestial sore), “wan dou chuang” (pea sore),“fu dou chuang” (bran sore), and“dou zhen” (pox-rash).This frequent changes of disease titles in its history is a significant mark of the evolution of TCM recognition on smallpox related to its treatment and prevention, and folk-social customs.It was not until the Republican period that the title of“pox-rash” was substituted by smallpox, a specific title for this viral infection.This is also the outcome showing the important position of TCM treatment and prevention for smallpox replaced by the preventive method of modern smallpox vaccination.

  6. Vaccine herd effect.

    Science.gov (United States)

    Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

    2011-09-01

    Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines.

  7. 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.

  8. 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.

  9. The Development of Vaccination and the Discoveries of Louis Pasteur.

    Science.gov (United States)

    Williams, James

    1992-01-01

    Describes the development of vaccination and provides a brief biographical sketch of the life and work of Pasteur. Describes historical practices related to vaccination before Pasteur did his work, including variolation as practiced by the ancient Chinese and Jenner's use of smallpox. (PR)

  10. The Development of Vaccination and the Discoveries of Louis Pasteur.

    Science.gov (United States)

    Williams, James

    1992-01-01

    Describes the development of vaccination and provides a brief biographical sketch of the life and work of Pasteur. Describes historical practices related to vaccination before Pasteur did his work, including variolation as practiced by the ancient Chinese and Jenner's use of smallpox. (PR)

  11. Anthrax and Other Vaccines: Use in the U.S. Military

    Science.gov (United States)

    2013-05-16

    effective with fewer adverse effects than antibiotics or other treatments – Enable force projection by providing continuous, long-lasting protection...Botulinum Toxoids* • Tularemia Vaccine* • Smallpox vaccine (Vaccinia Virus, Cell Culture-derived)* • Equine Encephalitis Virus Vaccines* *Investigational New...DATSD(CBD) Medical Biological Defense: Current Capabilities – Therapeutics • Therapeutics – Various antibiotics for treatment of exposure to

  12. Biological Weapons and Bioterorism Threats: The Role of Vaccines in Protecting the Military and Civilian Sectors

    Science.gov (United States)

    2013-05-16

    lowest risk, most effective protection – More effective with fewer adverse effects than antibiotics or other treatments – Enable force projection by...Plague • Anthrax Vaccine Adsorbed • Botulinum Toxoids* • Tularemia Vaccine* • Smallpox vaccine (Vaccinia Virus, Cell Culture-derived)* • Equine

  13. Smallpox DNA Vaccine Protects Nonhuman Primates Against Lethal Monkeypox

    Science.gov (United States)

    2004-05-01

    threatening (e.g., eczema vac- cinatum, encephalitis, and progressive vaccinia) (6). Serious adverse events that are not necessarily causally associated...This outbreak (71 suspected and 35 laboratory-confirmed cases as of 8 July 2003) may have been transmitted from prairie dogs that were infected after

  14. SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Nyoman Kumara Rai

    2012-09-01

    Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun. Disini hanya akan dibahas pelaksanaan vaksinasi cacar dan BCG secara simultan di Jawa dan Bali, mengingat pelaksanaannya yang sudah memasuki tahun kedua.

  15. SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Nyoman Kumara Rai

    2012-09-01

    Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun. Disini hanya akan dibahas pelaksanaan vaksinasi cacar dan BCG secara simultan di Jawa dan Bali, mengingat pelaksanaannya yang sudah memasuki tahun kedua.

  16. Smallpox Vaccination Information for Women Who Are Pregnant or Breastfeeding

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  17. 75 FR 3244 - Prospective Grant of Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses

    Science.gov (United States)

    2010-01-20

    ... Antibodies Against Smallpox/Orthopoxviruses AGENCY: National Institutes of Health, Public Health Service...: Concerns that variola (smallpox) virus might be used as a biological weapon have led to the recommendation... prevention of smallpox, it is well documented that various adverse reactions in individuals have been caused...

  18. 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,…

  19. 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.

  20. 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

  1. 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…

  2. 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…

  3. From foe to friend: geographical and environmental factors and the control and eradication of smallpox in India.

    Science.gov (United States)

    Bhattacharya, Sanjoy

    2003-01-01

    Due to the highly visible nature of the disease, smallpox received a lot of attention from the colonial and independent Indian governments. An assessment of the changing official views about the impact of geographical and environmental factors on modes of variola causation and control presents insights into themes that are generally ignored in the existing historiography. Rather than being synchronised efforts, imposed top-down, provincial level officials in charge of running vaccination programmes were able to retain a great degree of autonomy and shape the nature of local immunisation drive. As a result, vaccination work in the country was often disjointed, marked by official disagreements about the usefulness of certain strategies and technological inputs, with these trends being most noticeable in rural areas. Thus, this study seeks to highlight the importance of recognising--and studying--the fractured nature of medical and public health administration in the South Asian sub-continent.

  4. The epidemic of smallpox in Guangdong Province and its prevention and treatment in the Republican period%民国时期广东的天花流行与防治

    Institute of Scientific and Technical Information of China (English)

    陈丽楠; 刘玲娣

    2014-01-01

    民国时期,广东几乎每年都有天花疫情发生.为了应对传染病,广东省建立了卫生行政及传染病防治机构,并自制牛痘疫苗;相关机构按周、月、年对疫情进行统计,并定期上报,以了解疫情进展.同时,还成立了传染病医院收容天花患者.港口检疫则将天花列为重点检查对象.为了推广牛痘接种,政府与社会合作,组织大规模的“种痘运动”,以儿童、学生和年轻人作为主要接种对象,并借助媒体积极宣传天花防治知识.%During the Republican period,the smallpox broke out in high frequency almost annually in Guangdong.In response to infectious diseases,the Guangdong government established the Health Administration and institutions for infectious disease's prevention and treatment,and prepared smallpox vaccine by themselves.In order to grasp the situation of the epidenmic,related institutions collected epidemic data weekly,monthly,and annually with the statistics reported regularly.Meanwhile,infectious diseasc hospital was established for smallpox patients.Harbor quarantine put smallpox as a key target of inspection.With the joint effort of the government and social organizations,massive "vaccination campaigns" was organized to promote vaccination,in which children,students and young people were the main subjects for inoculations.Prevention knowledge and anti-epidemic concept towards smallpox have been actively publicized and improved by media.

  5. 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.

  6. GeneChip Resequencing of the Smallpox Virus Genome Can Identify Novel Strains: a Biodefense Application▿

    Science.gov (United States)

    Sulaiman, Irshad M.; Tang, Kevin; Osborne, John; Sammons, Scott; Wohlhueter, Robert M.

    2007-01-01

    We developed a set of seven resequencing GeneChips, based on the complete genome sequences of 24 strains of smallpox virus (variola virus), for rapid characterization of this human-pathogenic virus. Each GeneChip was designed to analyze a divergent segment of approximately 30,000 bases of the smallpox virus genome. This study includes the hybridization results of 14 smallpox virus strains. Of the 14 smallpox virus strains hybridized, only 7 had sequence information included in the design of the smallpox virus resequencing GeneChips; similar information for the remaining strains was not tiled as a reference in these GeneChips. By use of variola virus-specific primers and long-range PCR, 22 overlapping amplicons were amplified to cover nearly the complete genome and hybridized with the smallpox virus resequencing GeneChip set. These GeneChips were successful in generating nucleotide sequences for all 14 of the smallpox virus strains hybridized. Analysis of the data indicated that the GeneChip resequencing by hybridization was fast and reproducible and that the smallpox virus resequencing GeneChips could differentiate the 14 smallpox virus strains characterized. This study also suggests that high-density resequencing GeneChips have potential biodefense applications and may be used as an alternate tool for rapid identification of smallpox virus in the future. PMID:17182757

  7. 天花生物恐怖风险下最优疫苗接种比例%Optimal proportion of immunized populations under different smallpox bioterrorist attack risks

    Institute of Scientific and Technical Information of China (English)

    许晴; 祖正虎; 张文斗; 徐致靖; 黄培堂; 郑涛

    2012-01-01

    天花是最危险的生物剂之一,目前全世界已经消除天花疾病,但发生天花生物恐怖袭击的可能性仍然存在.大规模接种天花疫苗是最有效的天花生物恐怖预防措施,但有可能会导致大量接种者产生严重的不良反应甚至死亡.因此,在存在天花恐怖事件可能性但尚未发生的当前,保有一定比例的天花免疫人群会减少真正发生时的整体损失.本文从最小化质量调整生命年损失的角度,探讨国家在不同天花生物恐怖袭击风险下应保有的最佳免疫人群比例.%Smallpox is one of the most dangerous biological agents. Although smallbox has been eliminated globally, the possibility of smallpox being used during a bioterrorist attack still exists. Large-scale smallpox vaccination is the most effective measure against smallpox bioterrorism, but may lead to serious side effects and even death. Therefore, retaining a certain proportion of immunized populations will reduce the overall losses in case of smallpox bioterrorist incidents. Based on minimized quality-adjusted life years losses, this article explored the optimal proportion of immunized populations that a country shoulol retain under the different smallpox bioterrorist attack risks.

  8. A varíola, uma antiga inimiga Smallpox, an old foe

    Directory of Open Access Journals (Sweden)

    Hermann G. Schatzmayr

    2001-12-01

    Full Text Available A varíola acompanhou o homem por muitos séculos, causando mortes e lesões graves e irreversíveis. Usada como arma biológica em situações de guerra, volta a ser tema de discussão no mundo exatamente por essa possibilidade, apesar de ter sido erradicada das Américas em 1971, e do mundo em 1977. Os dados acumulados durante as Campanhas de Erradicação, mostram que a infecção se disseminava com relativa lentidão, através de contato muito próximo do receptor com o paciente. Infecções sub-clínicas em não-vacinados eram raras e vacinações de bloqueio em torno de novos casos, desde que estes fossem identificados e confirmados com rapidez, eram capazes de impedir a disseminação da infecção. As transmissões indiretas através de aerossóis eram menos comuns. Vacinados mesmo uma única vez, raramente apresentavam doença grave, no caso de reinfecção. A possibilidade de uso do vírus da varíola como arma biológica deve ser considerada como real, apesar de, com base nos conhecimentos atuais, serem necessárias suspensões virais de alta potência, lançadas muito próximo das pessoas a serem atingidas em grande número.Smallpox has accompanied mankind for centuries, causing deaths and permanent lesions. Used in the past as a biological weapon during wars, it has come into focus again precisely because of this renewed possibility, although the disease has been eradicated in the Americas since 1971 and worldwide since 1977. Data gathered during the eradication campaigns show that the disease spread relatively slowly through close contacts between patients and susceptibles. Sub-clinical infection in non-vaccinated individuals was a rare event, and blockade vaccination surrounding new cases (as long as these cases were confirmed early was able to prevent the disease from spreading in the community. Even with only one dose, vaccinated individuals rarely developed a serious case of the disease upon reinfection. The use of smallpox as

  9. 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.

  10. 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.

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

    Science.gov (United States)

    2012-03-01

    Story of Eradicating a Worldwide Killer (New York: Prometheus Books, 2009), 32. 15 Bill Frist, When Every Moment Counts: What You Need to Know...Hammond, and Leonard Cole, eds., Essentials of Terror Medicine (New York, NY: Springer, 2009), 203. 46 Henderson and Borio, “Smallpox and Monkeypox,” 629...Shapira, Hammond, and Cole, eds., Essentials of Terror Medicine , 204; Centers for Disease Control and Prevention, Division of Bioterrorism

  12. [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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 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

  16. 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)

  17. Demographic impact of vaccination: a review.

    Science.gov (United States)

    Bonanni, P

    1999-10-29

    Vaccination is one of the most powerful means to save lives and to increase the level of health of mankind. However, the impact of immunization against the most threatening infectious agents on life expectancy has been the object of a still open debate. The main issues are: the relative influence of nutrition and infectious diseases on demographic patterns of populations; the possibility that lives saved thanks to vaccination are subsequently lost due to other competing causes of death; the positive indirect effect of immunization on other causes of death. With regard to past evidence, several data from the United Kingdom and Scandinavian countries show that the widespread use of smallpox vaccination starting at the beginning of the nineteenth century resulted in a marked and sustained decline not only of smallpox-related deaths, but also of the overall crude death rate, and contributed greatly to an unprecedented growth of European population. As to the present, it is estimated that 3 million children are saved annually by vaccination, but 2 million still die because they are not immunized. Tetanus, measles and pertussis are the main vaccine-preventable killers in the first years of life. Data from Bangladesh show that full implementation of EPI vaccines has the potential of reducing mortality by almost one half in children aged 1-4 years. Recent progress in the development of vaccines against agents responsible for much mortality in the developing countries make it possible to forecast a further substantial reduction of deaths for infectious diseases in the next century.

  18. Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975.

    Science.gov (United States)

    Massung, R F; Liu, L I; Qi, J; Knight, J C; Yuran, T E; Kerlavage, A R; Parsons, J M; Venter, J C; Esposito, J J

    1994-06-01

    We analyzed the 186,102 base pairs (bp) that constitute the entire DNA genome of a highly virulent variola virus isolated from Bangladesh in 1975. The linear, double-stranded molecule has relatively small (725 bp) inverted terminal repeat (ITR) sequences containing three 69-bp direct repeat elements, a 54-bp partial repeat element, and a 105-base telomeric end-loop that can be maximally base-paired to contain 17 mismatches. Proximal to the right-end ITR sequences are another seven 69-bp elements and a 53- and a 27-bp partial element. Sequence analysis showed 187 closely spaced open reading frames specifying putative major proteins containing > or = 65 amino acids. Most of the virus proteins correspond to proteins in current databases, including 150 proteins that have > 90% identity to major gene products encoded by vaccinia virus, the smallpox vaccine. Variola virus has a group of proteins that are truncated compared with vaccinia virus counterparts and a smaller group of proteins that are elongated. The terminal regions encode several novel proteins and variants of other poxvirus proteins that potentially augment variola virus transmissibility and virulence for its only natural host, humans.

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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....... In a quasi-experimental study two doses before and after 9months compared with one dose of MV after 9months of age reduced mortality by 59% (25-81%). BCG-revaccination significantly enhanced BCG's effect against overall child mortality in two RCTs. In a natural experiment study of OPV campaigns over a 13......-year-period in Guinea-Bissau, each additional dose of OPV was associated with a 13% (4-21%) reduction in mortality rate. The beneficial NSEs of smallpox vaccination for survival increased significantly with the number of smallpox vaccination scars. INTERPRETATION: Revaccination with live vaccines led...

  1. [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.

  2. Social contact networks and disease eradicability under voluntary vaccination.

    Directory of Open Access Journals (Sweden)

    Ana Perisic

    2009-02-01

    Full Text Available Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant, a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior-infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease

  3. Social contact networks and disease eradicability under voluntary vaccination.

    Science.gov (United States)

    Perisic, Ana; Bauch, Chris T

    2009-02-01

    Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant), a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior-infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease eradicability in

  4. 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.

  5. Enfrentando el bioterrorismo: aspectos epidemiológicos, clínicos y preventivos de la viruela Confronting bioterrorism: epidemiologic, clinical, and preventive aspects of smallpox

    Directory of Open Access Journals (Sweden)

    Carlos Franco-Paredes

    2003-08-01

    Organization has dramatically switched to the preservation of the remaining virus after the September 2001 terrorist events in the U.S. along with the intentional release of Bacillus anthracis in the U.S. The risk of intentional release of Variola virus constitutes a minimal, yet possible risk. A smallpox epidemic could have a devastating impact due to its elevated morbidity and mortality that would inflict in non-immune human population, in addition to the ensuing panic and social unrest. Therefore, the development of national preparedness and response plans along with the availability of smallpox vaccine to be used in the post-exposure phase represent a fundamental part of the preventive efforts to cope with bioterrorism. Reestablishing a preventive vaccination program was recently recommended by the Advisory Committee on Immunization Practices (ACIP. However, the vaccine currently available has historically been associated with serious adverse reactions, even death. Thus, this recommendation has not been universally accepted. To counter an epidemic of smallpox, medical personnel in the frontline need to be prepared with updated smallpox infor mation to identify, diagnose, isolate, and treat cases if a bioterrorist attack should occur. Herein we present an in-depth review for health care personnel with relevant epidemiologic, clinical, and preventive information on smallpox.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. The evolution of poxvirus vaccines.

    Science.gov (United States)

    Sánchez-Sampedro, Lucas; Perdiguero, Beatriz; Mejías-Pérez, Ernesto; García-Arriaza, Juan; Di Pilato, Mauro; Esteban, Mariano

    2015-04-01

    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.

  11. 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.

  12. Drought, smallpox, and emergence of Leishmania braziliensis in northeastern Brazil.

    Science.gov (United States)

    Sousa, Anastácio Q; Pearson, Richard

    2009-06-01

    Cutaneous leishmaniasis caused by Leishmania (Vianna) braziliensis is a major health problem in the state of Ceará in northeastern Brazil. We propose that the disease emerged as a consequence of the displacement of persons from Ceará to the Amazon region following the Great Drought and smallpox epidemic of 1877-1879. As the economic and social situation in Ceará deteriorated, approximately 55,000 residents migrated to the Amazon region to find work, many on rubber plantations. Those that returned likely introduced L. (V.) brazilensis into Ceará, where the first cases of cutaneous leishmaniasis were reported early in the 20th century. The absence of an animal reservoir in Ceará, apart from dogs, supports the hypothesis. The spread of HIV/AIDS into the region and the possibility of concurrent cutaneous leishmaniasis raise the possibility of future problems.

  13. 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.

  14. Challenges Confronted in Smallpox Vaccination and DNA Smallpox Vaccine%天花预防接种面临的挑战与DNA痘苗

    Institute of Scientific and Technical Information of China (English)

    高一彤; 曲京华; 赵玫

    2006-01-01

    介绍美国重新启动种痘的动因,LIR、A27L、A33R、B5R基因痘苗建立、修饰的Ankara痘苗和Lister基因缺失痘苗动物保护力、安全试验、临床研究现状及预防天花、人类猴痘的前景.

  15. Advances in the development of inactivated virus vaccines.

    Science.gov (United States)

    Stauffer, Fausto; El-Bacha, Tatiana; Da Poian, Andrea T

    2006-11-01

    Vaccine discovery stands out as one of the public health interventions that has achieved the greatest impact in world's health. Vaccination is the most effective means of disease prevention, especially for viral infections. Starting with the use of smallpox vaccine by Jenner in the late 1700s, the technology for vaccine development has seen numerous advances. Currently, vaccines available for human viral illness are based on live attenuated (e.g. measles, mumps, and rubella), inactivated (e.g. hepatitis A) and recombinant (e.g. hepatitis B) viruses. Among these, inactivated vaccines are known for their easy production and safety. The present article reviews the literature and patents related to the mechanisms used for viral inactivation, mainly chemical and physical procedures, including the novel strategies that are currently being explored and that have been recently patent protected.

  16. 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

  17. 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

  18. 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.

  19. Dismantling the Taboo against Vaccines in Pregnancy

    Science.gov (United States)

    de Martino, Maurizio

    2016-01-01

    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. PMID:27338346

  20. Vaccines as a trigger for myopathies.

    Science.gov (United States)

    Orbach, H; Tanay, A

    2009-11-01

    Vaccines are considered to be among the greatest medical discoveries, credited with the virtual eradication of some diseases and the consequent improved survival and quality of life of the at-risk population. With that, vaccines are among the environmental factors implicated as triggers for the development of inflammatory myopathies. The sporadic reports on vaccine-induced inflammatory myopathies include cases of hepatitis B virus, bacillus Calmette-Guérin, tetanus, influenza, smallpox, polio, diphtheria, diphtheria-pertussis-tetanus, combination of diphtheria with scarlet fever and diphtheria-pertussis-tetanus with polio vaccines. However, a significant increase in the incidence of dermatomyositis or polymyositis after any massive vaccination campaign has not been reported in the literature. In study patients with inflammatory myopathies, no recent immunization was recorded in any of the patients. Moreover, after the 1976 mass flu vaccination, no increase in the incidence of inflammatory myopathies was observed. Although rare, macrophagic myofasciitis has been reported following vaccination and is attributed to the aluminium hydroxide used as an adjuvant in some vaccines. Prospective multicenter studies are needed to identify potential environmental factors, including vaccines, as potential triggers for inflammatory myopathies.

  1. 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.

  2. 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.

  3. 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 o

  4. 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.

  5. 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 o

  6. New effective chemically synthesized anti-smallpox compound NIOCH-14.

    Science.gov (United States)

    Mazurkov, Oleg Yu; Kabanov, Alexey S; Shishkina, Larisa N; Sergeev, Alexander A; Skarnovich, Maksim O; Bormotov, Nikolay I; Skarnovich, Maria A; Ovchinnikova, Alena S; Titova, Ksenya A; Galahova, Darya O; Bulychev, Leonid E; Sergeev, Artemiy A; Taranov, Oleg S; Selivanov, Boris A; Tikhonov, Alexey Ya; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2016-05-01

    Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The 'therapeutic window' varied from 1 day before infection to 6 days post-infection (p.i.) to achieve 100-60 % survival rate. The administration of NIOCH-14 and ST-246 to mice resulted in a significant reduction of ectromelia virus titres in organs examined as compared with the control and also reduced pathological changes in the lungs 6 days p.i. Oral administration of NIOCH-14 and ST-246 to ICR mice and marmots challenged with monkeypox virus as compared with the control resulted in a significant reduction of virus production in the lungs and the proportion of infected mice 7 days p.i. as well as the absence of disease in marmots. Significantly lower proportions of infected mice and virus production levels in the lungs as compared with the control were demonstrated in experiments after oral administration of NIOCH-14 and ST-246 to ICR mice and immunodeficient SCID mice challenged with variola virus 3 and 4 days p.i., respectively. The results obtained suggest good prospects for further study of the chemical compound NIOCH-14 to create a new smallpox drug on its basis.

  7. HPV vaccine

    Science.gov (United States)

    ... cervix - HPV vaccine; Abnormal Pap smear - HPV vaccine; Vaccination - HPV vaccine ... and Gynecologists. Committee opinion No. 641: human papillomavirus vaccination. Obstet Gynecol . 2015;126(3):e38-e43. PMID: ...

  8. 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.

  9. 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...... ulcer at the site of his childhood BCG vaccination. At the time of examination, a 3 x 1.5 cm fleshy and secreting ulcer was found on the shoulder. Biopsy revealed SCC, and the tumour was surgically removed. In conclusion, chronic ulcers, especially those originating in chronically inflamed skin, should...

  10. The Development of an AIDS Mucosal Vaccine

    Directory of Open Access Journals (Sweden)

    Xian Tang

    2010-01-01

    Full Text Available It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1, a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.

  11. Vaccine hesitancy: parental, professional and public responsibility.

    Science.gov (United States)

    Di Pietro, Maria Luisa; Poscia, Andrea; Teleman, Adele Anna; Maged, Davide; Ricciardi, Walter

    2017-01-01

    The opposition to vaccinations is a well-known phenomenon that dates back to the Victorian age when it was self-limited by the awareness of the importance to be protected against fearsome infectious diseases. In the XX century, the mass use of vaccination has - instead - consented to eradicate or drastically reduce the burden of diseases such as smallpox and polio. These positive effects of the vaccination campaigns have blurred out, if not erased, the memory of the tragic consequences of the past's widespread diseases, leading people to underestimate the severity of the harm that vaccinations prevent. In recent years, a complex mixture of contextual factors have promoted an amplification of that paradoxical situation, leading experts to study causes and consequences of the so called "vaccine hesitancy". Several studies have shown the impact for children and for the community of the refusal or hesitation towards vaccinations from different points of view, including epidemiological, clinical, social and economic evaluation. This article provides an analysis of vaccine hesitancy from an ethical perspective: parental, professional and public responsibilities are analysed and described according to the "responsibility of the fathers towards the children", as articulated by Hans Jonas in 1979.

  12. Les hasards de la variole The hazards of smallpox

    Directory of Open Access Journals (Sweden)

    Jean-Marc Rohrbasser

    2011-12-01

    Full Text Available La nécessité d’un calcul ayant pour fin d’estimer un risque peut être révoquée en doute lorsqu’il s’agit de prendre une décision en situation d’incertitude, a fortiori lorsqu’il s’agit d’une question de vie ou de mort. Dans la controverse engagée sur l’opportunité d’inoculer la variole, la position de D’Alembert constitue un cas exemplaire de scepticisme portant sur l’application des mathématiques, et en l’occurrence du calcul des probabilités, à des décisions relatives à la vie humaine. D’Alembert, en effet, conteste aux mathématiques sociales le pouvoir de rendre compte de phénomènes humains en y cherchant des régularités et des formalisations sans dissocier les dimensions mathématiques et probabilistes des dimensions philosophiques et éthiques. En suivant le débat qui, au milieu du xviiie siècle, se déroule entre le mathématicien français et son homologue suisse Daniel Bernoulli, on assiste à l’un des épisodes de la lente gestation des notions de prise de risque, de décision et de rationalité.The necessity of a calculation aiming to evaluate a risk can be revoked in doubt when the question is to make a decision in a situation of uncertainty, all the more when the question is about life or death. In the controversy opened on the opportunity to inoculate the smallpox, D'Alembert’s position constitutes an exemplary case of scepticism concerning the application of the mathematics, and in this particular case the probability theory, to decisions relative to the human life. D’Alembert, indeed, disputes in the social mathematics the power to describe human phenomena by looking for regularities and for formalizations without separating the mathematical and probability dimensions of the philosophic and ethical ones. By following the debate which, in the middle of the 18th century, takes place between the French mathematician and his Swiss counterpart Daniel Bernoulli, we attend one of the

  13. Smallpox Vaccinations and the Portuguese in Macao%种牛痘与澳门葡人

    Institute of Scientific and Technical Information of China (English)

    伊莎贝尔·莫赖斯

    2007-01-01

    牛痘接种法发明以后,葡、西、英等殖民国家进行了积极的推广.本文对澳门接受牛痘的过程进行研究,探讨澳门作为一个由殖民政府管理的港口是如何积极支持传播欧洲医学的最新成果的.并对牛痘与贸易、殖民的关系也进行了分析.

  14. What to Do After You've Gotten the Smallpox Vaccine

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  15. Someone You Are Close to May Get the Smallpox Vaccine: What You Should Know and Do

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

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

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Sørup, Signe;

    2016-01-01

    -up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36-0.81] for mortality due...

  17. 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.

  18. 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.

  19. 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.

  20. From empiricism to rational design: a personal perspective of the evolution of vaccine development.

    Science.gov (United States)

    De Gregorio, Ennio; Rappuoli, Rino

    2014-07-01

    Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner - and later Pasteur - inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.

  1. Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine adjuvants enhances immune responses and protection of mice from vaccinia virus challenge.

    Science.gov (United States)

    Xiao, Yuhong; Zeng, Yuhong; Alexander, Edward; Mehta, Shyam; Joshi, Sangeeta B; Buchman, George W; Volkin, David B; Middaugh, C Russell; Isaacs, Stuart N

    2013-01-02

    The stockpiling of live vaccinia virus vaccines has enhanced biopreparedness against the intentional or accidental release of smallpox. Ongoing research on future generation smallpox vaccines is providing key insights into protective immune responses as well as important information about subunit-vaccine design strategies. For protein-based recombinant subunit vaccines, the formulation and stability of candidate antigens with different adjuvants are important factors to consider for vaccine design. In this work, a non-tagged secreted L1-protein, a target antigen on mature virus, was expressed using recombinant baculovirus technology and purified. To identify optimal formulation conditions for L1, a series of biophysical studies was performed over a range of pH and temperature conditions. The overall physical stability profile was summarized in an empirical phase diagram. Another critical question to address for development of an adjuvanted vaccine was if immunogenicity and protection could be affected by the interactions and binding of L1 to aluminum salts (Alhydrogel) with and without a second adjuvant, CpG. We thus designed a series of vaccine formulations with different binding interactions between the L1 and the two adjuvants, and then performed a series of vaccination-challenge experiments in mice including measurement of antibody responses and post-challenge weight loss and survival. We found that better humoral responses and protection were conferred with vaccine formulations when the L1-protein was adsorbed to Alhydrogel. These data demonstrate that designing vaccine formulation conditions to maximize antigen-adjuvant interactions is a key factor in smallpox subunit-vaccine immunogenicity and protection.

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. Vaccinia Virus: A Tool for Research and Vaccine Development

    Science.gov (United States)

    Moss, Bernard

    1991-06-01

    Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy.

  7. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  8. Cancer Vaccines

    Science.gov (United States)

    ... Genetics Services Directory Cancer Prevention Overview Research Cancer Vaccines On This Page What is the immune system? ... cells recognized by the immune system? What are vaccines? What are cancer vaccines? How do cancer preventive ...

  9. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. Vaccine Hesitancy.

    Science.gov (United States)

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

    2015-11-01

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

  16. Potent T cell Responses Induced by Single DNA Vaccine Boosted with Recombinant Vaccinia Vaccine

    Institute of Scientific and Technical Information of China (English)

    Lianxing Liu; Chao Qiu; Yang Huang; Jianqing Xu; Yiming Shao

    2013-01-01

    Plasmid DNA,an effective vaccine vector,can induce both cellular and humoral immune responses.However,plasmid DNA raises issues concerning potential genomic integration after injection.This issue should be considered in preclinical studies.Tiantan vaccinia virus (TV) has been most widely utilized in eradicating smallpox in China.This virus has also been considered as a successful vaccine vector against a few infectious diseases.Potent T cell responses through T-cell receptor (TCR) could be induced by three injections of the DNA prime vaccine followed by a single injection of recombinant vaccinia vaccine.To develop a safer immunization strategy,a single DNA prime followed by a single recombinant Tiantan vaccinia (rTV) AIDS vaccine was used to immunize mice.Our data demonstrated that one DNA prime/rTV boost regimen induced mature TCR activation with high functional avidity,preferential T cell Vβ receptor usage and high sensitivity to anti-CD3 antibody stimulation.No differences in T cell responses were observed among one,two or three DNA prime/rTV boost regimens.This study shows that one DNA prime/rTV boost regimen is sufficient to induce potent T cell responses against HIV.

  17. Population-level differences in disease transmission: a Bayesian analysis of multiple smallpox epidemics.

    Science.gov (United States)

    Elderd, Bret D; Dwyer, Greg; Dukic, Vanja

    2013-09-01

    Estimates of a disease's basic reproductive rate R0 play a central role in understanding outbreaks and planning intervention strategies. In many calculations of R0, a simplifying assumption is that different host populations have effectively identical transmission rates. This assumption can lead to an underestimate of the overall uncertainty associated with R0, which, due to the non-linearity of epidemic processes, may result in a mis-estimate of epidemic intensity and miscalculated expenditures associated with public-health interventions. In this paper, we utilize a Bayesian method for quantifying the overall uncertainty arising from differences in population-specific basic reproductive rates. Using this method, we fit spatial and non-spatial susceptible-exposed-infected-recovered (SEIR) models to a series of 13 smallpox outbreaks. Five outbreaks occurred in populations that had been previously exposed to smallpox, while the remaining eight occurred in Native-American populations that were naïve to the disease at the time. The Native-American outbreaks were close in a spatial and temporal sense. Using Bayesian Information Criterion (BIC), we show that the best model includes population-specific R0 values. These differences in R0 values may, in part, be due to differences in genetic background, social structure, or food and water availability. As a result of these inter-population differences, the overall uncertainty associated with the "population average" value of smallpox R0 is larger, a finding that can have important consequences for controlling epidemics. In general, Bayesian hierarchical models are able to properly account for the uncertainty associated with multiple epidemics, provide a clearer understanding of variability in epidemic dynamics, and yield a better assessment of the range of potential risks and consequences that decision makers face.

  18. Vaccines against biologic agents: uses and developments.

    Science.gov (United States)

    Ales, Noel C; Katial, Rohit K

    2004-03-01

    concentrations of organisms may overcome vaccine protection. Finally,exposure may not be immediately noted until it is too late to vaccinate, as was the case with anthrax. Even in a case, such as smallpox, in which postexposure vaccination is possible, patients will still develop disease, and the health care system may be overwhelmed. The United States government has been defensively planning and researching the use of vaccines and chemoprophylaxis against any potential biologic agents since at least 1953, and resources are still lacking. There are inadequate stockpiles of vaccine to protect the entire population. The pharmaceutical industry also lacks a means of mass producing vaccines ina short timeframe. There is no policy in place for the use of vaccines that are yet unlicensed and experimental but may be the only therapy in the event ofa terrorist attack. Investigations into these solutions have been instituted only after the September 11, 2001, attacks heightened the awareness of terrorism. Although vaccination is an effective means of prophylaxis and a means of terminating epidemics or treating active disease, there is also resistance from the general public. In some instances there is a lack of acceptance of vaccines, or the risk of side effects is too great. In other cases, a questionable benefit does not justify the expense of mass vaccination. Because of this uncertainty, mass vaccination is deemed an impractical solution to the threat of bioterrorism. Extending vaccination with most vaccines to include all members of society who may be first responders in the event of an attack should be considered. In all instances, the benefit-to-risk must be weighed ratio when deciding how and when to offer preemptive prophylaxis to protect society from a real but unknown threat.

  19. Recombinant MVA vaccines: dispelling the myths.

    Science.gov (United States)

    Cottingham, Matthew G; Carroll, Miles W

    2013-09-06

    Diseases such as HIV/AIDS, tuberculosis, malaria and cancer are prime targets for prophylactic or therapeutic vaccination, but have proven partially or wholly resistant to traditional approaches to vaccine design. New vaccines based on recombinant viral vectors expressing a foreign antigen are under intense development for these and other indications. One of the most advanced and most promising vectors is the attenuated, non-replicating poxvirus MVA (modified vaccinia virus Ankara), a safer derivative of the uniquely successful smallpox vaccine. Despite the ability of recombinant MVA to induce potent humoral and cellular immune responses against transgenic antigen in humans, especially when used as the latter element of a heterologous prime-boost regimen, doubts are occasionally expressed about the ultimate feasibility of this approach. In this review, five common misconceptions over recombinant MVA are discussed, and evidence is cited to show that recombinant MVA is at least sufficiently genetically stable, manufacturable, safe, and immunogenic (even in the face of prior anti-vector immunity) to warrant reasonable hope over the feasibility of large-scale deployment, should useful levels of protection against target pathogens, or therapeutic benefit for cancer, be demonstrated in efficacy trials.

  20. 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.

  1. A two-dose schedule for immunization of infants using a more concentrated DPT-vaccine.

    Science.gov (United States)

    Mangay-Angara, A; Fulgencio, L; Casabal, G; Gudani, L; Sumpaico, J; Ocampo, A; Nagel, J; Hagenaars, A M; van Hemert, P A; Cohen, H

    1978-01-01

    In a controlled field-trial in infants in the Philippines, a two-dose schedule with an interval of 6 months between injections using a concentrated adsorbed DPT-vaccine was evaluated. The serologic response against the three components in the vaccine was satisfactory, whereas the side-effects in the concentrated vaccine group did not differ from those observed in a control DPT group. After two injections, the coverage percentage with DPT-vaccine was shown to be higher than 70%. Two implications of the introduction of the two-dose DPT-immunization schedule are discussed, i.e. (a) the possibility of using it as the nucleus of a complete schedule including immunization against poliomyelitis, BCG, smallpox and measles, and (b) the consequences which the interval of 6 months might have on the epidemiological spread of B. pertussis infections.

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

    Directory of Open Access Journals (Sweden)

    Eric M Mucker

    Full Text Available 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.

  3. Human CD4+ T cell epitopes from vaccinia virus induced by vaccination or infection.

    Directory of Open Access Journals (Sweden)

    J Mauricio Calvo-Calle

    2007-10-01

    Full Text Available Despite the importance of vaccinia virus in basic and applied immunology, our knowledge of the human immune response directed against this virus is very limited. CD4(+ T cell responses are an important component of immunity induced by current vaccinia-based vaccines, and likely will be required for new subunit vaccine approaches, but to date vaccinia-specific CD4(+ T cell responses have been poorly characterized, and CD4(+ T cell epitopes have been reported only recently. Classical approaches used to identify T cell epitopes are not practical for large genomes like vaccinia. We developed and validated a highly efficient computational approach that combines prediction of class II MHC-peptide binding activity with prediction of antigen processing and presentation. Using this approach and screening only 36 peptides, we identified 25 epitopes recognized by T cells from vaccinia-immune individuals. Although the predictions were made for HLA-DR1, eight of the peptides were recognized by donors of multiple haplotypes. T cell responses were observed in samples of peripheral blood obtained many years after primary vaccination, and were amplified after booster immunization. Peptides recognized by multiple donors are highly conserved across the poxvirus family, including variola, the causative agent of smallpox, and may be useful in development of a new generation of smallpox vaccines and in the analysis of the immune response elicited to vaccinia virus. Moreover, the epitope identification approach developed here should find application to other large-genome pathogens.

  4. 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.

  5. 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

  6. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  7. [On the vaccination before and after Jenner].

    Science.gov (United States)

    de Micheli, Alfredo; Izaguirre-Avila, Raúl

    2011-01-01

    The expression "inoculation" of smallpox was first employed by doctor Emanuel Timone, native of the Greek island of Chios and graduated from the Universities of Padua and Oxford. This method was largely employed in the XVIII century. Nevertheless, in 1798, the English physician Edward Jenner published the results of his observartions and his own experience with "vaccination", i. e. the inoculation of cowpox. These were exposed in his book "Inquiry into the causes and effects of the variolae vaccinae". This method soon substituted the variolization. However it must to be mentioned that, starting from 1770, vaccination was already performed in northern Europe by non medical personnel as for example the school teacher Peter Plett. Notwithstanding some initial opposition, vaccination quickly spreaded throughout Europe. It arrived to Spain in 1801 and thence was transferred to Spanish America and Philippines Islands with the expedition leaded by doctor Francisco Xavier Balmis. This expedition reached New Spain in June 1804, and remained there until February 1805 when embarked addressing to Philippines Islands. The other expeditionary group, leaded by doctor José Salvani, addressed toward Colombia, Peru and Bolivia, where Salvani died.

  8. Chasing Jenner's vaccine: revisiting cowpox virus classification.

    Directory of Open Access Journals (Sweden)

    Darin S Carroll

    Full Text Available Cowpox virus (CPXV is described as the source of the first vaccine used to prevent the onset and spread of an infectious disease. It is one of the earliest described members of the genus Orthopoxvirus, which includes the viruses that cause smallpox and monkeypox in humans. Both the historic and current literature describe "cowpox" as a disease with a single etiologic agent. Genotypic data presented herein indicate that CPXV is not a single species, but a composite of several (up to 5 species that can infect cows, humans, and other animals. The practice of naming agents after the host in which the resultant disease manifests obfuscates the true taxonomic relationships of "cowpox" isolates. These data support the elevation of as many as four new species within the traditional "cowpox" group and suggest that both wild and modern vaccine strains of Vaccinia virus are most closely related to CPXV of continental Europe rather than the United Kingdom, the homeland of the vaccine.

  9. Rabies Vaccine

    Science.gov (United States)

    ... high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers should be offered rabies vaccine. The vaccine should also be considered for: (1) ...

  10. What the world's religions teach, applied to vaccines and immune globulins.

    Science.gov (United States)

    Grabenstein, John D

    2013-04-12

    For millennia, humans have sought and found purpose, solace, values, understanding, and fellowship in religious practices. Buddhist nuns performed variolation against smallpox over 1000 years ago. Since Jenner developed vaccination against smallpox in 1796, some people have objected to and declined vaccination, citing various religious reasons. This paper reviews the scriptural, canonical basis for such interpretations, as well as passages that support immunization. Populous faith traditions are considered, including Hinduism, Buddhism, Jainism, Judaism, Christianity, and Islam. Subjects of concern such as blood components, pharmaceutical excipients of porcine or bovine origin, rubella strain RA 27/3, and cell-culture media with remote fetal origins are evaluated against the religious concerns identified. The review identified more than 60 reports or evaluations of vaccine-preventable infectious-disease outbreaks that occurred within religious communities or that spread from them to broader communities. In multiple cases, ostensibly religious reasons to decline immunization actually reflected concerns about vaccine safety or personal beliefs among a social network of people organized around a faith community, rather than theologically based objections per se. Themes favoring vaccine acceptance included transformation of vaccine excipients from their starting material, extensive dilution of components of concern, the medicinal purpose of immunization (in contrast to diet), and lack of alternatives. Other important features included imperatives to preserve health and duty to community (e.g., parent to child, among neighbors). Concern that 'the body is a temple not to be defiled' is contrasted with other teaching and quality-control requirements in manufacturing vaccines and immune globulins. Health professionals who counsel hesitant patients or parents can ask about the basis for concern and how the individual applies religious understanding to decision-making about

  11. Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox.

    Science.gov (United States)

    Guimarães, Ana P; de Souza, Felipe R; Oliveira, Aline A; Gonçalves, Arlan S; de Alencastro, Ricardo B; Ramalho, Teodorico C; França, Tanos C C

    2015-02-16

    Recently we constructed a homology model of the enzyme thymidylate kinase from Variola virus (VarTMPK) and proposed it as a new target to the drug design against smallpox. In the present work, we used the antivirals cidofovir and acyclovir as reference compounds to choose eleven compounds as leads to the drug design of inhibitors for VarTMPK. Docking and molecular dynamics (MD) studies of the interactions of these compounds inside VarTMPK and human TMPK (HssTMPK) suggest that they compete for the binding region of the substrate and were used to propose the structures of ten new inhibitors for VarTMPK. Further docking and MD simulations of these compounds, inside VarTMPK and HssTMPK, suggest that nine among ten are potential selective inhibitors of VarTMPK. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. 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.

  13. Edible vaccines.

    OpenAIRE

    Artnzen, C J

    1997-01-01

    Vaccines were the result of trial and error research until molecular biology and genetic engineering made possible the creation of of many new and improved vaccines. New vaccines need to be inexpensive, easily administered, and capable of being stored and transported without refrigeration; without these characteristics, developing countries find it difficult to adopt vaccination as the central strategy for preventing their most devastating diseases. The authors describe a promising approach t...

  14. Periodontal vaccine

    OpenAIRE

    Ranjan Malhotra; Anoop Kapoor; Vishakha Grover; Aaswin Kaur Tuli

    2011-01-01

    Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of pe...

  15. HPV Vaccine

    Science.gov (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness HPV Vaccine KidsHealth > For Teens > HPV Vaccine Print A A A What's in this article? ... 11 or 12 through age 21 If needed, kids can get the vaccine starting at age 9. continue How Does the ...

  16. DNA vaccines

    Science.gov (United States)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  17. FLU VACCINATION

    CERN Document Server

    2007-01-01

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

  18. Periodontal vaccine

    Directory of Open Access Journals (Sweden)

    Ranjan Malhotra

    2011-01-01

    Full Text Available Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of periodontal vaccine would not only prevent and modulate periodontal disease, but also enhance the quality of life of people for whom periodontal treatment cannot be easily obtained. The aim of the research should be development of a multispecies vaccine targeting the four prime periodontal pathogens, viz. Porphyromonas gingivalis, T. forsythus, T. denticola and A. comitans. Success is still elusive in case of periodontal vaccine due to the complex etiopathogenesis of the disease.

  19. Voluntary Vaccination through Self-organizing Behaviors on Locally-mixed Social Networks.

    Science.gov (United States)

    Shi, Benyun; Qiu, Hongjun; Niu, Wenfang; Ren, Yizhi; Ding, Hong; Chen, Dan

    2017-06-01

    Voluntary vaccination reflects how individuals weigh the risk of infection and the cost of vaccination against the spread of vaccine-preventable diseases, such as smallpox and measles. In a homogeneously mixing population, the infection risk of an individual depends largely on the proportion of vaccinated individuals due to the effects of herd immunity. While in a structured population, the infection risk can also be affected by the structure of individuals' social network. In this paper, we focus on studying individuals' self-organizing behaviors under the circumstance of voluntary vaccination in different types of social networks. Specifically, we assume that each individual together with his/her neighbors forms a local well-mixed environment, where individuals meet equally often as long as they have a common neighbor. We carry out simulations on four types of locally-mixed social networks to investigate the network effects on voluntary vaccination. Furthermore, we also evaluate individuals' vaccinating decisions through interacting with their "neighbors of neighbors". The results and findings of this paper provide a new perspective for vaccination policy-making by taking into consideration human responses in complex social networks.

  20. ["For a history of vaccination in Brazil": an unpublished manuscript by Norberto and Macedo].

    Science.gov (United States)

    Lopes, Myriam Bahia; Polito, Ronald

    2007-01-01

    The manuscript "Para uma história da vacina no Brasil" [For a history of vaccination in Brazil] was unearthed in the archives of Instituto Histórico Geográfico Brasileiro (IHGB) along with other texts by Joaquim Manoel de Macedo. It was written in partnership with Joaquim Norberto in 1859 in response to a request by the Emperor to the institute. Its characteristics mark it out as a founding text: its arguments are designed to establish who really introduced the smallpox vaccine to Brazil and to resolve the controversy between the Marquis of Barbacena and a surgeon, Francisco Mendes Ribeiro de Vasconcellos. It analyzes the documents that provide the basis for both versions and consolidates the beginning of the history of vaccination in Brazilian territory in 1878, which was subsequently recognized by IHGB.

  1. 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

  2. Flu Vaccination

    CERN Multimedia

    2006-01-01

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

  3. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

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

  4. Flu Vaccination

    CERN Document Server

    2006-01-01

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

  5. FLU VACCINATION

    CERN Multimedia

    2006-01-01

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

  6. Flu Vaccination

    CERN Multimedia

    2006-01-01

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

  7. 天花疫苗的研究现状和进展%Research Progress in Smallpox Vaccine

    Institute of Scientific and Technical Information of China (English)

    刘丽; 汪巨峰; 李波

    2013-01-01

    目的 对现行天花疫苗和天花疫苗的研究进展进行综述,为天花疫苗的研究和应用提供参考.方法 通过查阅近年来与天花疫苗有效性和安全性研究相关的国内外文献,进行归纳总结.结果 扩大天花疫苗储备已成为全球性的需要,传统天花疫苗的有效性已得到充分验证,但会引起很多副作用,需要开发更为安全有效的天花疫苗.人们先后研发了几种不同类型的天花疫苗,包括细胞培养的活病毒疫苗、复制型和复制缺陷型的减毒活疫苗、蛋白亚单位疫苗、DNA亚单位疫苗、载体亚单位疫苗等.结论 减毒活疫苗与传统疫苗相比具有更好的安全性,但其免疫原性相对较低,目前,亚单位天花疫苗的研究仍处于起步阶段,需要进行更多和更深入的研究来验证其临床应用的可行性.新型天花疫苗的研发对增加使用者依从性、提高疫苗免疫效果和安全性具有重要意义.

  8. Heterogeneity in the A33 Protein Impacts the Cross-Protective Efficacy of a Candidate Smallpox DNA Vaccine

    Science.gov (United States)

    2008-01-01

    1997). By 24-h post-transfection, COS cells were labeled with 35S-methionine/ cystine for 4 h and lysed using 4% zwit- tergent buffer (4% zwittergent...3753–3762. Roper, R.L., Wolffe, E.J., Weisberg, A., Moss, B., 1998. The envelope protein encoded by the A33R gene is required for formation of actin...Smith, G.L., Way, M., 1999. Interactions be- tween vaccinia virus IEV membrane proteins and their roles in IEV assembly and actin tail formation . J

  9. Leptospirosis vaccines

    OpenAIRE

    Jin Li; Wang Zhijun; Węgrzyn Alicja

    2007-01-01

    Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the...

  10. Patent landscape of countermeasures against smallpox and estimation of grant attraction capability through patent landscape data.

    Science.gov (United States)

    Mayburd, Anatoly L; Kedia, Govind; Evans, Haydn W; Kaslival, Pritesh C

    2010-11-01

    The study was concerned with countermeasures against a possible smallpox outbreak. In the process of assessment 18 landscaping sectors were defined and described, the advantages and drawbacks of the corresponding countermeasures being reviewed. The data of the previously published influenza landscape were revisited. The current economic climate of deficit cutting (austerity) also puts emphasis on the optimization of capital investment. We used the materials of the landscape to define and analyze metrics of capital placement optimization. Value score was obtained by fitting patent landscape internals to the sale price of individual patents. Success score was obtained as a product of a-priori parameters that measure likelihood of emergence of a marketable product in a technological sector. Both scores were combined in a qualitative metric. Our methodology defined weight as a product of the sector size by the success score. We hypothesized - based on the material of two landscapes- that a life cycle of a technology begins in IP space with a high patent quality low volume "bud" of low weight, reaches maximum weight and then weight falls again when the technology becomes outdated. The weight and the annual dynamic of weight can serve a measure of investment risk and return. In this report we modeled investment by issue of government grants or purchase of patents by government. In the smallpox landscape the number of patents purchased by government agencies was the highest in the sectors with the highest weight and the trend was confirmed by the count of NIH grants issued in support of the technological sectors. In the influenza landscape only grant issue count was statistically meaningful and the trend was also confirmed. To better fit the grant support levels, the weight expression was optimized by using training coefficients. We propose to use value scores for evaluation of individual patent publications/company portfolios and to use weights for assessment of

  11. 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.

  12. 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

  13. Activity, specificity, and probe design for the smallpox virus protease K7L.

    Science.gov (United States)

    Aleshin, Alexander E; Drag, Marcin; Gombosuren, Naran; Wei, Ge; Mikolajczyk, Jowita; Satterthwait, Arnold C; Strongin, Alex Y; Liddington, Robert C; Salvesen, Guy S

    2012-11-16

    The K7L gene product of the smallpox virus is a protease implicated in the maturation of viral proteins. K7L belongs to protease Clan CE, which includes distantly related cysteine proteases from eukaryotes, pathogenic bacteria, and viruses. Here, we describe its recombinant high level expression, biochemical mechanism, substrate preference, and regulation. Earlier studies inferred that the orthologous I7L vaccinia protease cleaves at an AG-X motif in six viral proteins. Our data for K7L suggest that the AG-X motif is necessary but not sufficient for optimal cleavage activity. Thus, K7L requires peptides extended into the P7 and P8 positions for efficient substrate cleavage. Catalytic activity of K7L is substantially enhanced by homodimerization, by the substrate protein P25K as well as by glycerol. RNA and DNA also enhance cleavage of the P25K protein but not of synthetic peptides, suggesting that nucleic acids augment the interaction of K7L with its protein substrate. Library-based peptide preference analyses enabled us to design an activity-based probe that covalently and selectively labels K7L in lysates of transfected and infected cells. Our study thus provides proof-of-concept for the design of inhibitors and probes that may contribute both to a better understanding of the role of K7L in the virus life cycle and the design of novel anti-virals.

  14. Selecting Viruses for the Seasonal Influenza Vaccine

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  15. Seasonal Flu Vaccine Safety and Pregnant Women

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  16. 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

  17. Lyon Playfair (1818-1898) and compulsory vaccination.

    Science.gov (United States)

    Butler, A

    2006-08-01

    Lyon Playfair was born in India but brought up by his uncle in St Andrews. He studied medicine in Glasgow and Edinburgh but never practised as a doctor. Instead he worked for the chemist Thomas Graham in London and then studied for a PhD with Liebig in Germany. While serving on a government commission he became very interested in public health, particularly the control of infectious diseases. In 1883, while a member of parliament, he made a passionate speech in support of a government bill in favour of compulsory vaccination against smallpox. He was violently attacked for his speech in a pamphlet by William White, an adherent of the teachings of the Swedish mystic Emanuel Swedenborg. Playfair died in 1898 and is buried in St Andrews.

  18. [Seeds against smallpox: Joaquim Vás and the scientific translation of bananeira brava seeds in Goa, India (1894-1930)].

    Science.gov (United States)

    Roque, Ricardo

    2004-01-01

    In 1914, in the former Portuguese colony of Goa, India, the physician António Joaquim Vás announced the discovery of a wonderful treatment for smallpox, entailing clinical application of seeds from the bananeira brava (Heliconia biabi Sw.m.), a plant remedy allegedly derived from Indian medical practices. The present article explores the circumstances surrounding the successes and failures of this discovery. The concept of scientific translation is used to interpret the transformation of bananeira brava seeds into an early twentieth-century remedy for smallpox. This transfer from indigenous use to scientific therapeutic constitutes the creation of a quasi-medicine, that is, a case of 'medium translation'. Although these seeds occupy a problematic place within the program of scientific translation, they enjoyed active circulation within science and remained a part of medical practices for combating smallpox.

  19. 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.

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

    Science.gov (United States)

    Yuan, Jun-liang; Wang, Shuang-kun; Guo, Xiao-juan

    2016-01-01

    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. PMID:27478662

  1. A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination.

    Science.gov (United States)

    Huang, Xiaoxing; Lu, Bin; Yu, Wenbo; Fang, Qing; Liu, Li; Zhuang, Ke; Shen, Tingting; Wang, Haibo; Tian, Po; Zhang, Linqi; Chen, Zhiwei

    2009-01-01

    Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels ( approximately 2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (approximately 10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.

  2. A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination.

    Directory of Open Access Journals (Sweden)

    Xiaoxing Huang

    Full Text Available Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA and a novel replication-competent modified vaccinia Tian Tan (MVTT for inducing neutralizing antibodies (Nabs via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels ( approximately 2-3-fold of anti- SARS-CoV neutralizing antibodies (Nabs than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (approximately 10-fold higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.

  3. [Plans for the establishment of central vaccination committees in the institutionalization of Medicine in Colombia].

    Science.gov (United States)

    Frias Nuñez, M

    1993-01-01

    The fight against smallpox epidemics in the Granada at the end of the 18th and beginning of the 19th centuries involved a whole series of actions which demonstrated the new ways of treating the disease. First the application of the innoculation and then the vaccination coincided with a greater general concern for the health of the population. At this time and especially with the arrival of José Celestino Mutis on Latin-American soil science in Colombia embarked upon an institutionalization process which also involved Medicine. José Salvany's proposals of stablishing Central Vaccination Committees were made in this context. The analysis of these proposals and their contribution towards "establishing institutional spaces" are the axes upon which this study is based.

  4. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  5. Ear Infection and Vaccines

    Science.gov (United States)

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

  6. Adults Need Vaccines, Too!

    Science.gov (United States)

    ... turn JavaScript on. Feature: Adult Vaccinations Adults Need Vaccines, Too! Past Issues / Summer 2015 Table of Contents ... of the millions of adults not receiving the vaccines you need? What vaccines do you need? All ...

  7. Vaccinations during Pregnancy

    Science.gov (United States)

    ... X Home > Pregnancy > Prenatal care > Vaccinations and pregnancy Vaccinations and pregnancy E-mail to a friend Please ... date before you get pregnant. What is a vaccination? A vaccination is a shot that contains a ...

  8. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.

  9. 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

  10. Vaccination priorities.

    Science.gov (United States)

    Steffen, Robert; Baños, Ana; deBernardis, Chiara

    2003-02-01

    Selection of immunizations should be based on requirements and on risk of infection. According to the International Health Regulations, many countries require yellow fever vaccination and proof thereof as the International Certificate of vaccination. Additionally selected countries require proof of vaccination against cholera and meningococcal disease. A consultation for travel health advice is always an opportunity to ascertain that routine immunizations have been performed. Recommended immunizations often are more important for traveller's health than the required or routine ones. The most frequent vaccine preventable infection in non-immune travellers to developing countries is hepatitis A with an average incidence rate of 0.3% per month; in high risk backpackers or foreign-aid-volunteers this rate is 2.0%. Many immunizations are recommended for special risk groups only: there is a growing tendency in many countries to immunize all young travellers to developing countries against hepatitis B, as it is uncertain who will voluntarily or involuntarily get exposed. The attack rate of influenza in intercontinental travel is estimated to be 1%. Immunity against poliomyelitis remains essential for travel to Africa and parts of Asia. Many of the 0.2-0.4% who experience an animal bite are at risk of rabies. Typhoid fever is diagnosed with an incidence rate of 0.03% per month among travellers to the Indian subcontinent, North and West Africa (except Tunisia), and Peru, elsewhere this rate is 10-fold lower. Meningococcal disease, Japanese encephalitis, cholera and tuberculosis have been reported in travellers, but these infections are rare in this population. Although no travel health vaccine is cost beneficial, most professionals will offer protection against the frequent risks, while most would find it ridiculous to use all available vaccines in every traveller. It is essentially an arbitrary decision made on the risk level one wishes to recommend protection--but the

  11. Gel-eletroforese no diagnóstico da varíola Gel-electrophoresis in the smallpox diagnosis

    Directory of Open Access Journals (Sweden)

    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.

  12. One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT(ZCI) protects animals against pathogenic viral challenge.

    Science.gov (United States)

    Yu, Wenbo; Fang, Qing; Zhu, Weijun; Wang, Haibo; Tien, Po; Zhang, Linqi; Chen, Zhiwei

    2010-02-25

    To combat variola virus in bioterrorist attacks, it is desirable to develop a noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was historically used to eradicate the smallpox in China, we generated a modified VTT (MVTT(ZCI)) by removing the hemagglutinin gene and an 11,944bp genomic region from HindIII fragment C2L to F3L. MVTT(ZCI) was characterized for its host cell range in vitro and preclinical safety and efficacy profiles in mice. Despite replication-competency in some cell lines, unlike VTT, MVTT(ZCI) did not cause death after intracranial injection or body weight loss after intranasal inoculation. MVTT(ZCI) did not replicate in mouse brain and was safe in immunodeficient mice. MVTT(ZCI) induced neutralizing antibodies via the intranasal route of immunization. One time intranasal immunization protected animals from the challenge of the pathogenic vaccinia WR strain. This study established proof-of-concept that the attenuated replicating MVTT(ZCI) may serve as a safe noninvasive smallpox vaccine candidate.

  13. Polio Vaccine

    Science.gov (United States)

    ... Health Resources Share Polio Vaccine What is polio?Poliomyelitis (polio, for short) is a serious illness that can cause paralysis (when you can't move your arms and legs) or even death. Polio is caused by a virus. The virus can be spread by drinking water ...

  14. Vexing Vaccines

    Science.gov (United States)

    Bowman, Darcia Harris

    2004-01-01

    Schools play a key role in ensuring that children are being immunized against diseases, but conflicting research is making enforcement difficult. This article discusses a growing trend of vaccine avoidance and the endless supply of conflicting information and research about immunization safety. Despite the controversy, many people appear to accept…

  15. Rotavirus Vaccine

    Science.gov (United States)

    ... including a severe allergy to latex. Babies with "severe combined immunodeficiency" (SCID) should not get rotavirus vaccine. Babies who have had a type of bowel blockage called "intussusception" should not get ... with moderate or severe diarrhea or vomiting. Check with your doctor if ...

  16. Valuing vaccination

    Science.gov (United States)

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

    2014-01-01

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

  17. Varicella (Chickenpox) Vaccine

    Science.gov (United States)

    ProQuad® (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine, Varicella Vaccine) ... up to about 1 person in 5) and measles-like rash (about 1 person in 20) than MMR and varicella vaccines given separately. Moderate Problems:Seizure (jerking or staring) ...

  18. 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.

  19. Pharmacokinetic and pharmacodynamic modeling to determine the dose of ST-246 to protect against smallpox in humans.

    Science.gov (United States)

    Leeds, Janet M; Fenneteau, Frederique; Gosselin, Nathalie H; Mouksassi, Mohamad-Samer; Kassir, Nastya; Marier, J F; Chen, Yali; Grosenbach, Doug; Frimm, Annie E; Honeychurch, Kady M; Chinsangaram, Jarasvech; Tyavanagimatt, Shanthakumar R; Hruby, Dennis E; Jordan, Robert

    2013-03-01

    Although smallpox has been eradicated, the United States government considers it a "material threat" and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection with a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than 4-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.

  20. Your Baby's First Vaccines

    Science.gov (United States)

    ... Link Vaccines & Immunizations Immunization Schedules Your Child's First Vaccines Format: Select one PDF [335 KB] RTF [260 ... child will get one or more of these vaccines today: DTaP Hib Hepatitis B Polio PCV13 Why ...

  1. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... Directory Cancer Prevention Overview Research Human Papillomavirus (HPV) Vaccines On This Page What are human papillomaviruses? Which ... infections? Can HPV infections be prevented? What HPV vaccines are available? Who should get the HPV vaccines? ...

  2. Vaccines Stop Illness

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  3. Vaccines and Thimerosal

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Thimerosal in Vaccines Recommend on Facebook Tweet Share Compartir Thimerosal is ... harm. Thimerosal prevents the growth of bacteria in vaccines. Thimerosal is added to vials of vaccine that ...

  4. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: Meningococcal Vaccines ... or her parents, and the doctor. Why the Vaccines Are Recommended Meningococcal disease is caused by a ...

  5. Vaccines.gov

    Science.gov (United States)

    ... supported by science, on vaccine safety. Are your child’s vaccines up to date? Getting all recommended vaccines on time can protect your child from serious diseases. Protect your community! Did you ...

  6. Vaccine-Preventable Disease Photos

    Science.gov (United States)

    Home | About | A-Z | Contact | Follow Vaccine Information You Need VACCINE BASICS Evaluating Online Health Information FAQs How Vaccines Work Importance of Vaccines Paying for Vaccines State Immunization Programs ...

  7. Immunology Update: New Vaccines.

    Science.gov (United States)

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  8. Adjuvants for allergy vaccines

    National Research Council Canada - National Science Library

    Moingeon, Philippe

    2012-01-01

    .... Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts...

  9. Hepatitis B Vaccine

    Science.gov (United States)

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

  10. "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

  11. Development of eczema vaccinatum in atopic mouse models and efficacy of MVA vaccination against lethal poxviral infection.

    Directory of Open Access Journals (Sweden)

    Jarmila Knitlova

    Full Text Available Smallpox vaccine based on live, replicating vaccinia virus (VACV is associated with several potentially serious and deadly complications. Consequently, a new generation of vaccine based on non-replicating Modified vaccinia virus Ankara (MVA has been under clinical development. MVA seems to induce good immune responses in blood tests, but it is impossible to test its efficacy in vivo in human. One of the serious complications of the replicating vaccine is eczema vaccinatum (EV occurring in individuals with atopic dermatitis (AD, thus excluding them from all preventive vaccination schemes. In this study, we first characterized and compared development of eczema vaccinatum in different mouse strains. Nc/Nga, Balb/c and C57Bl/6J mice were epicutaneously sensitized with ovalbumin (OVA or saline control to induce signs of atopic dermatitis and subsequently trans-dermally (t.d. immunized with VACV strain Western Reserve (WR. Large primary lesions occurred in both mock- and OVA-sensitized Nc/Nga mice, while they remained small in Balb/c and C57Bl/6J mice. Satellite lesions developed in both mock- and OVA-sensitized Nc/Nga and in OVA-sensitized Balb/c mice with the rate 40-50%. Presence of mastocytes and eosinophils was the highest in Nc/Nga mice. Consequently, we have chosen Nc/Nga mice as a model of AD/EV and tested efficacy of MVA and Dryvax vaccinations against a lethal intra-nasal (i.n. challenge with WR, the surrogate of smallpox. Inoculation of MVA intra-muscularly (i.m. or t.d. resulted in no lesions, while inoculation of Dryvax t.d. yielded large primary and many satellite lesions similar to WR. Eighty three and 92% of mice vaccinated with a single dose of MVA i.m. or t.d., respectively, survived a lethal i.n. challenge with WR without any serious illness, while all Dryvax-vaccinated animals survived. This is the first formal prove of protective immunity against a lethal poxvirus challenge induced by vaccination with MVA in an atopic organism.

  12. Vaccines and vaccinations. The strategic issues.

    Science.gov (United States)

    Ford, R B

    2001-05-01

    The rapid proliferation of companion animal vaccines, advances in diagnostic and vaccine technology, and concerns over vaccine safety are clearly among the most important issues practicing veterinarians face as we enter the 21st century. Although many would argue that these are already issues, the future promises to be especially challenging as the vaccines we currently use and the protocols we recommend undergo unprecedented review.

  13. Research progress in response strategies to smallpox bioterrorism%生物恐怖视角下的天花应对策略研究进展

    Institute of Scientific and Technical Information of China (English)

    祖正虎; 许晴; 张文斗; 徐致靖; 黄培堂; 郑涛

    2013-01-01

    Emergency prevention and control of smallpox transmission in the context of bioterrorism require effective response strategies. This paper began by describing the general process of computational experiments on smallpox response strategies. Then,the current achievement of this method was summarized in terms of the experimental environment, the computational model and intervention strategies. Finally, problems with smallpox response strategy simulation and directions of further research were discussed.%生物恐怖视角下天花传播的应急防控需要科学的应对策略.本文首先介绍天花应对策略计算实验的一般过程,然后从实验环境、计算模型及干预策略3个方面总结当前的研究及取得的进展,并就天花应对策略模拟存在的问题及进一步研究方向进行讨论.

  14. Dried influenza vaccines : Over the counter vaccines

    NARCIS (Netherlands)

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

    2010-01-01

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

  15. Dried influenza vaccines : Over the counter vaccines

    NARCIS (Netherlands)

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

    2010-01-01

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

  16. Guillain-Barré Syndrome (GBS) and Flu Vaccine

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  17. 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

  18. Mucosal vaccination of fish

    NARCIS (Netherlands)

    Rombout, J.H.W.M.; Kiron, V.

    2014-01-01

    Among the novel vaccination methods, mucosal vaccination seems to possess all the desired criteria. The chapter reviews the state-of-the-art knowledge regarding this type of vaccination with a focus on their uptake, immune stimulation, and where possible, discusses their potential as future vaccines

  19. History of vaccination.

    Science.gov (United States)

    Plotkin, Stanley

    2014-08-26

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

  20. Nucleic Acid Vaccines

    Institute of Scientific and Technical Information of China (English)

    LU Shan

    2004-01-01

    @@ Anew method of immunization was discovered in the early 1990s. Several research groups independently demonstrated that direct inoculation of DNA plasmids coding for a specific protein antigen could elicit immune responses against that antigen[1-4].Since in theory the mRNA molecules also have the potential to be translated into the protein antigen, this vaccination approach was officially named by WHO as the nucleic acid vaccination even though the term DNA vaccine has been used more commonly in the literature. This novel approach is considered the fourth generation of vaccines after live attenuated vaccines, killed or inactivated vaccines and recombinant protein based subunit vaccines.

  1. Vaccine adverse events.

    Science.gov (United States)

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  2. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

    significant losses in aquacultural enterprises but vaccination methods implemented since the 1990s have demonstrated their role as one of the most efficient disease control strategies. These have been particularly successful with regard to bacterial diseases in Norwegian salmon farming where multivalent...... vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...

  3. Vaccines against poverty

    OpenAIRE

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vacc...

  4. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603

  5. Vaccine Effectiveness - How Well Does the Seasonal Flu Vaccine Work?

    Science.gov (United States)

    ... flu viruses. What are the benefits of flu vaccination? While how well the flu vaccine works can ... older people have weaker immune responses to flu vaccination, should they still get vaccinated? Despite the fact ...

  6. Typhoid fever vaccination strategies.

    Science.gov (United States)

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

    2015-06-19

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

  7. A case of exemplarity: C. F. Rottböll's history of smallpox inoculation in Denmark-Norway, 1766.

    Science.gov (United States)

    Eriksen, Anne

    2010-01-01

    Smallpox inoculation was one of the great discoveries of the 18th century and has been written into the grand narrative of medical progress, describing the taming of epidemic disease. Setting the perspective of progress aside, the article explores how this medical innovation was situated in 18th-century society and culture. The aim is to investigate how medical practice was intertwined with social structure and cultural patterns. The article takes its case from a book published in Copenhagen in 1766 by Professor C. F. Rottböll, former Head Physician of the Royal Inoculation House in Copenhagen. Being the first medical treatise on inoculation in Denmark-Norway, the book also has a historical section followed by a collection of reports and letters written by a number of other authors from various parts of the kingdom. Through close reading, the article explores how the introduction of the new technique was described in the texts. The reports were written to present practice and discuss cases. In doing so, they also presented a variety of other concerns so that a diversity of aims and intentions are added to the medical ones. The social and rhetorical strategies employed illuminate social ambition and systems of patronage, as well as understandings of history and of truth.

  8. The sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox.

    Science.gov (United States)

    Gubser, Caroline; Smith, Geoffrey L

    2002-04-01

    Camelpox virus (CMPV) and variola virus (VAR) are orthopoxviruses (OPVs) that share several biological features and cause high mortality and morbidity in their single host species. The sequence of a virulent CMPV strain was determined; it is 202182 bp long, with inverted terminal repeats (ITRs) of 6045 bp and has 206 predicted open reading frames (ORFs). As for other poxviruses, the genes are tightly packed with little non-coding sequence. Most genes within 25 kb of each terminus are transcribed outwards towards the terminus, whereas genes within the centre of the genome are transcribed from either DNA strand. The central region of the genome contains genes that are highly conserved in other OPVs and 87 of these are conserved in all sequenced chordopoxviruses. In contrast, genes towards either terminus are more variable and encode proteins involved in host range, virulence or immunomodulation. In some cases, these are broken versions of genes found in other OPVs. The relationship of CMPV to other OPVs was analysed by comparisons of DNA and predicted protein sequences, repeats within the ITRs and arrangement of ORFs within the terminal regions. Each comparison gave the same conclusion: CMPV is the closest known virus to variola virus, the cause of smallpox.

  9. Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures

    Directory of Open Access Journals (Sweden)

    Jennifer Garver

    2016-07-01

    Full Text Available In 2007, the United States– Food and Drug Administration (FDA issued guidance concerning animal models for testing the efficacy of medical countermeasures against variola virus (VARV, the etiologic agent for smallpox. Ectromelia virus (ECTV is naturally-occurring and responsible for severe mortality and morbidity as a result of mousepox disease in the murine model, displaying similarities to variola infection in humans. Due to the increased need of acceptable surrogate animal models for poxvirus disease, we have characterized ECTV infection in the BALB/c mouse. Mice were inoculated intranasally with a high lethal dose (125 PFU of ECTV, resulting in complete mortality 10 days after infection. Decreases in weight and temperature from baseline were observed eight to nine days following infection. Viral titers via quantitative polymerase chain reaction (qPCR and plaque assay were first observed in the blood at 4.5 days post-infection and in tissue (spleen and liver at 3.5 days post-infection. Adverse clinical signs of disease were first observed four and five days post-infection, with severe signs occurring on day 7. Pathological changes consistent with ECTV infection were first observed five days after infection. Examination of data obtained from these parameters suggests the ECTV BALB/c model is suitable for potential use in medical countermeasures (MCMs development and efficacy testing.

  10. Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures.

    Science.gov (United States)

    Garver, Jennifer; Weber, Lauren; Vela, Eric M; Anderson, Mike; Warren, Richard; Merchlinsky, Michael; Houchens, Christopher; Rogers, James V

    2016-07-22

    In 2007, the United States- Food and Drug Administration (FDA) issued guidance concerning animal models for testing the efficacy of medical countermeasures against variola virus (VARV), the etiologic agent for smallpox. Ectromelia virus (ECTV) is naturally-occurring and responsible for severe mortality and morbidity as a result of mousepox disease in the murine model, displaying similarities to variola infection in humans. Due to the increased need of acceptable surrogate animal models for poxvirus disease, we have characterized ECTV infection in the BALB/c mouse. Mice were inoculated intranasally with a high lethal dose (125 PFU) of ECTV, resulting in complete mortality 10 days after infection. Decreases in weight and temperature from baseline were observed eight to nine days following infection. Viral titers via quantitative polymerase chain reaction (qPCR) and plaque assay were first observed in the blood at 4.5 days post-infection and in tissue (spleen and liver) at 3.5 days post-infection. Adverse clinical signs of disease were first observed four and five days post-infection, with severe signs occurring on day 7. Pathological changes consistent with ECTV infection were first observed five days after infection. Examination of data obtained from these parameters suggests the ECTV BALB/c model is suitable for potential use in medical countermeasures (MCMs) development and efficacy testing.

  11. Bob H. Reinhardt: The End of A Global Pox. America and the Eradication of Smallpox in the Cold War Era : The University of North Carolina Press, Chapel Hill, 2015, 268 pp., Hard cover, Illustrated, Figure, Maps, Table, Notes, Bibliography, Index., $39.95.

    Science.gov (United States)

    Imperato, Pascal James

    2017-04-01

    This review examines in detail Bob H. Reinhardt's meticulous analyses of smallpox eradication within the broad context of American liberalism, Cold War politics, and the exercise of technological, medical, and political power on the part of the United States. As a result, his book provides a unique perspective on the eradication of smallpox.

  12. Neurologic complications of vaccinations.

    Science.gov (United States)

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

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

  13. Vaccination: An Act of Love

    Science.gov (United States)

    ... benefits of vaccines. For this reason, we created Vaccination Week in the Americas to get vaccines to ... and no one gets left behind. Help the vaccination teams when they come to your town, your ...

  14. Nasal spray flu vaccine (image)

    Science.gov (United States)

    The flu vaccine can also be administered as a nasal spray instead of the usual injection method. It can be ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should not ...

  15. Vaccinations for Adults with Diabetes

    Science.gov (United States)

    Vaccinations for Adults with Diabetes The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  16. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  17. Vaccines against poverty.

    Science.gov (United States)

    MacLennan, Calman A; Saul, Allan

    2014-08-26

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

  18. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

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

  19. Vaccine Associated Myocarditis

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2017-04-01

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

  20. 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.

  1. Allergic reactions to vaccines.

    Science.gov (United States)

    Wood, Robert A

    2013-09-01

    Anaphylactic reactions to vaccines are rare but do occur, and have been reported for nearly every vaccine. And while the reaction rate per each dose of vaccine is low, this is a common clinical question due in large part to the enormous numbers of vaccines administered. Reactions are most often due to vaccine constituents rather than the microbial components of the vaccine, but in many instances, the specific ingredient triggering the reaction cannot be definitively identified. Evaluation of patients with suspected vaccine reactions should begin by determining whether the symptoms and timing of the reaction were consistent with a true allergic reaction, followed by an assessment to determine whether the patient needs further doses of the vaccine in question, or similar vaccines, in the future. Skin and serologic testing to vaccines and vaccine constituents can then be performed to further assess the potential cause of the reaction and to develop a plan for future immunizations. Specific guidelines for the administration of influenza vaccines to egg allergic patients have been revised to allow virtually all patients to receive this vaccine in a straightforward manner. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Attenuvax® Measles Vaccine ... R-Vax® II (as a combination product containing Measles Vaccine, Rubella Vaccine) ... M-R® II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  3. The HPV Vaccination Crisis

    Science.gov (United States)

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

  4. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: ... vaccines are a good idea. Caring for Your Child After Immunization Your child might have a fever, soreness, and ...

  5. Vaccines and Pregnancy

    Science.gov (United States)

    ... best live chat Live Help Fact Sheets Share Vaccines and Pregnancy Thursday, 01 September 2016 In every ... risk. This sheet talks about whether exposure to vaccines may increase the risk for birth defects over ...

  6. Vaccines in Multiple Sclerosis.

    Science.gov (United States)

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

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  7. Pneumococcal Vaccines (PCV, PPSV)

    Science.gov (United States)

    ... Games, and the Internet Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your Child's Immunizations: ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, ...

  8. Adjuvants for malaria vaccines.

    Science.gov (United States)

    Coler, R N; Carter, D; Friede, M; Reed, S G

    2009-09-01

    There is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re-focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.

  9. Vaccine Safety Datalink

    Science.gov (United States)

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

  10. Generating memory with vaccination.

    Science.gov (United States)

    Castellino, Flora; Galli, Grazia; Del Giudice, Giuseppe; Rappuoli, Rino

    2009-08-01

    The goal of vaccination is to induce long-lasting protective immune memory. Although most vaccines induce good memory responses, the type of memory induced by different vaccines may be considerably different. In addition, memory responses to the same vaccine may be influenced by age, environmental and genetic factors. Results emerging from detailed and integrated profiling of immune-responses to natural infection or vaccination suggest that the type and duration of immune memory are largely determined by the magnitude and complexity of innate immune signals that imprint the acquired immune primary responses. Here we summarize results obtained from analyzing human immune memory responses to different types of vaccines. We will also discuss how extending clinical investigation to events occurring early after vaccination can help identify early predictive markers of protective memory and thus contribute to faster development of better and safer vaccines.

  11. Pharmacy management of vaccines.

    Science.gov (United States)

    Cannon, H Eric

    2007-09-01

    Although standard vaccines have traditionally been granted full coverage in managed care, the recent introduction of several novel vaccine products has necessitated the revision of pharmacy management strategies throughout the nation. To review pharmacy management strategies for a number of emerging vaccines, with unique plan perspectives from SelectHealth, an Intermountain Healthcare company serving approximately 500,000 members in Utah. Because several recently introduced vaccines target previously unaddressed diseases and carry higher costs than traditional vaccines, several plans have adapted a novel approach to manage vaccine coverage on an individual product basis. At SelectHealth, recently introduced vaccines for rotavirus, respiratory syncytial virus (RSV), herpes zoster, and human papillomavirus (HPV) have required special attention in terms of pharmacy management. After carefully weighing acquisition and administration costs, anticipated uptake and use, direct and indirect health care costs averted, and quality of life issues, plan leadership decided to cover many of the new vaccines (i.e., rotavirus, RSV, and herpes zoster) under a nonstandard vaccination benefit. However, because substantial cost savings and high use of the quadrivalent HPV vaccine was anticipated within SelectHealth, the plan decided to fully cover the product. Although they complicate traditional pharmacy management, novel vaccines provide clinical benefit that managed care organizations cannot ignore. One universal strategy will not suffice in managing all the different vaccines entering the market, and a tailored approach should be employed based on the individual characteristics and use of each product.

  12. Improving newcastle disease vaccination with homologous vaccines

    Science.gov (United States)

    All Newcastle disease viruses (NDVs) belong to a single serotype; however, current vaccine strains display important amino acid differences at the F and HN protein compared with virulent outbreak strains (vNDV). Previous studies have shown decreased viral shedding after challenge when vaccines were...

  13. Brucellosis vaccines for livestock.

    Science.gov (United States)

    Goodwin, Zakia I; Pascual, David W

    2016-11-15

    Brucellosis is a livestock disease responsible for fetal loss due to abortions. Worldwide, this disease has profound economic and social impact by reducing the ability of livestock producers to provide an adequate supply of disease-free meat and dairy products. In addition to its presence in domesticated animals, brucellosis is harbored in a number of wildlife species creating new disease reservoirs, which adds to the difficulty of eradicating this disease. Broad and consistent use of the available vaccines would contribute in reducing the incidence of brucellosis. Unfortunately, this practice is not common. In addition, the current brucellosis vaccines cannot provide sterilizing immunity, and in certain circumstances, vaccinated livestock are not protected against co-mingling Brucella-infected wildlife. Given that these vaccines are inadequate for conferring complete protection for some vaccinated livestock, alternatives are being sought, and these include genetic modifications of current vaccines or their reformulations. Alternatively, many groups have sought to develop new vaccines. Subunit vaccines, delivered as a combination of soluble vaccine plus adjuvant or the heterologous expression of Brucella epitopes by different vaccine vectors are currently being tested. New live attenuated Brucella vaccines are also being developed and tested in their natural hosts. Yet, what is rarely considered is the route of vaccination which could improve vaccine efficacy. Since Brucella infections are mostly transmitted mucosally, mucosal delivery of a vaccine has the potential of eliciting a more robust protective immune response for improved efficacy. Hence, this review will examine these questions and provide the status of new vaccines for livestock brucellosis.

  14. Advances in FIV vaccine technology

    OpenAIRE

    Uhl, Elizabeth W.; Martin, Marcus; Coleman, James K.; Yamamoto, Janet K.

    2008-01-01

    Advances in vaccine technology are occurring in the molecular techniques used to develop vaccines and in the assessment of vaccine efficacy, allowing more complete characterization of vaccine-induced immunity correlating to protection. FIV vaccine development has closely mirrored and occasionally surpassed the development of HIV-1 vaccine, leading to first licensed technology. This review will discuss technological advances in vaccine designs, challenge infection assessment, and characterizat...

  15. Adjuvants for Animal Vaccines.

    Science.gov (United States)

    Burakova, Yulia; Madera, Rachel; McVey, Scott; Schlup, John R; Shi, Jishu

    2017-06-15

    Vaccines are essential tools for the prevention and control of infectious diseases in animals. One of the most important steps in vaccine development is the selection of a suitable adjuvant. The focus of this review is the adjuvants used in vaccines for animals. We will discuss current commercial adjuvants and experimental formulations with attention to mineral salts, emulsions, bacterial-derived components, saponins, and several other immunoactive compounds. In addition, we will also examine the mechanisms of action for different adjuvants, examples of adjuvant combinations in one vaccine formulation, and challenges in the research and development of veterinary vaccine adjuvants.

  16. Vaccination for Disease

    Science.gov (United States)

    Oehen, Stephan; Hengartner, Hans; Zinkernagel, Rolf M.

    1991-01-01

    Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.

  17. 应用微量滴定法测定天花疫苗效力%Detection of the potency of smallpox vaccine by microtitration

    Institute of Scientific and Technical Information of China (English)

    董小曼; 董翊; 陈秀珍

    2007-01-01

    微量滴定法代替血球吸附法测定天花疫苗效力.通过对Vero细胞接种浓度和细胞病变判定时间的优化,确定了微量滴定法测定天花疫苗效力的方法,用Vero细胞微量滴定法和血球吸附法测定14批天花疫苗.两种滴定方法的检测结果差异有显著意义(P<0.05),二者存在正相关(r=0.76, 0.001<P<0.05)和直线回归(b=0.45, 0.001<P<0.05)关系,直线回归方程为=4.61+0.45x.微量滴定法变异系数CV为1.25%~2.89%.因此,微量滴定法敏感、可靠、操作简单、重复性好,可以代替血球吸附法.

  18. Vaccinations for pregnant women.

    Science.gov (United States)

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources.

  19. Emerging Vaccine Informatics

    Directory of Open Access Journals (Sweden)

    Yongqun He

    2010-01-01

    Full Text Available Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO has been initiated to integrate various vaccine data and support automated reasoning.

  20. Vaccines for allergy.

    Science.gov (United States)

    Linhart, Birgit; Valenta, Rudolf

    2012-06-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic.

  1. [Vaccines and pregnancy].

    Science.gov (United States)

    Tavares, Mariana Vide; Ramos, Vera Nobre; Tavares, Margarida; Moura, Paulo

    2011-12-01

    Routine vaccination is part of the pediatrics universe. In adulthood and particularly when women voluntarily access to medical care, immunization should be reviewed and updated. There are many doubts that generate in all health professionals anxiety and concern about the vaccination of a pregnant woman. This article aims to describe the immunological changes in pregnant women, to clarify the purpose of immunization during pregnancy, and to enumerate indications, contraindications and risks of vaccines of the Portuguese National Vaccine Plane and other vaccines against diseases with prevalence in other countries. Due to the medical and social impact of vaccination against seasonal influenza and influenza A (H1N1) in the winter of 2009, during an influenza (H1N1) pandemic flu, we make reference to the indications and vaccination against these infections in pregnancy.

  2. Un momento de reflexión acerca de las vacunas Just a moment for thinking about vaccines

    Directory of Open Access Journals (Sweden)

    G.G. Cáceres Bermejo

    2012-06-01

    Full Text Available Durante muchos siglos, los primeros atisbos de vacunación estuvieron ligados a la práctica de la variolización. En 1796 Edward Jenner desarrolló la primera vacuna contra la viruela: gracias a la vacunación se ha conseguido la erradicación de esta mortal enfermedad sobre el planeta. En otras enfermedades como el tétanos neonatal, la poliomielitis o el sarampión las campañas de vacunación han conseguido una drástica disminución de la morbi-mortalidad. Actualmente, estos logros conseguidos por las vacunas han producido una falsa percepción de ausencia de riesgo, en algunos casos han descendido las coberturas de vacunación, y se ha producido un aumento del número de casos y brotes de algunas enfermedades como el sarampión. A esta situación han contribuido los mensajes de algunos grupos contrarios a la vacunación que han atribuido a las vacunas una serie de efectos adversos que en ningún caso han sido probados por la comunidad científica.Throughout the last centuries, the first signs of vaccination were linked to variolation procedures. In 1796, Edward Jenner developed the first vaccine for smallpox: the world eradication of this mortal disease was achieved due to the vaccination. In other diseases, such as neonatal tetanus, poliomyelitis or measles, immunization programmes have drastically decreased morbidity and mortality. Nowadays, these achievements of vaccination have caused a false perception of lack of risk, causing a decrease in immunization coverage in some cases. There has been a considerable increase on reported cases and outbreaks of some diseases such as measles. The messages of anti-vaccination movements have contributed to generate this situation by associating some adverse effects with vaccines, but there is no scientific evidence to support it.

  3. 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

  4. Vaccine process technology.

    Science.gov (United States)

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

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

  5. Vaccines and Kawasaki disease.

    Science.gov (United States)

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

    2016-01-01

    The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

  6. Vaccination against seasonal flu

    CERN Multimedia

    2015-01-01

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

  7. Vaccination and neurological disorders

    Directory of Open Access Journals (Sweden)

    Anastasia Gkampeta

    2015-12-01

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

  8. Liver Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  9. HIV Infection and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals HIV Infection and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... percentage is less than 15%. Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  10. Renal Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  11. What Vaccines Do You Need?

    Science.gov (United States)

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

  12. HIV/AIDS and Vaccines

    Science.gov (United States)

    ... against the disease. Is There a Vaccine for HIV? No. There is currently no vaccine that will ... in this video! /* // ** // */ Why Do We Need an HIV Vaccine? Today, more people living with HIV than ...

  13. Vaccination in food allergic patients

    African Journals Online (AJOL)

    Important potential food allergens in vaccines include egg and gelatin. Rare cases of ... rabies vaccine: purified chick embryo cell (PCEC) culture vaccine; human diploid cell ... found in MMR, varicella, influenza, typhoid, yellow fever, Japanese.

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

    Science.gov (United States)

    Barraza, Leila; Schmit, Cason; Hoss, Aila

    2017-03-01

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

  15. Vaccine Treatment for Prostate Cancer

    Science.gov (United States)

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer Vaccine Treatment for Prostate Cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  16. Influenza Vaccine, Inactivated or Recombinant

    Science.gov (United States)

    ... die from flu, and many more are hospitalized.Flu vaccine can:keep you from getting flu, make flu ... inactivated or recombinant influenza vaccine?A dose of flu vaccine is recommended every flu season. Children 6 months ...

  17. NAPPA-Based Vaccines for a New Proteogenomics Approach for Public Health

    Directory of Open Access Journals (Sweden)

    Nicola Luigi Bragazzi

    2015-03-01

    Full Text Available Vaccinology was developed for the first time in 1796 when Jenner empirically implemented a vaccine against smallpox using animal-to-human cowpox inoculation. Since then, it has become a very complex science due to the merging of disciplines ranging from structural and functional, cellular and molecular biology and immunology to bioinformatics and nanobiotechnology, as well as systems biology and synthetic biology and engineering. In the frame of evidence-based medicine (EBM, evidence-based vaccinology emerged as an important sub-field: vaccinology has nowadays become more and more predictive and personalized. With the discovery that many patients with cancer develop antibodies against p53 (the so-called oncoantibodies, it was evident that oncoprotein are immunogenic and can be used for immunotherapeutics purposes. In this manuscript, we report Nucleic Acid Programmable Protein Arrays (NAPPA-based Quartz Crystal Microbalance (QCM measurement of p53 immunogenicity and kinetics, in the perspective of developing an effective p53 therapy. NAPPA-based QCM_D can be a useful platform for proving the immunogenicity of oncoprotein-based vaccines. Recently, the field of vaccinology has extended from vaccines for infectious diseases to vaccines not only preventive but also therapeutic for chronic-degenerative diseases such as cancer. Peptide-based immunotherapeutics has been proven to be quite effective for cancer treatment and NAPPA-based QCM_D has the promise of providing clinicians with quick, rapid and cheap measurement of oncoprotein kinetics and bindings with immune cells. Moreover, it can be a precious tool for implementing personalized and predictive vaccinology.

  18. DNA vaccines used for biodefense%生物防御用DNA疫苗

    Institute of Scientific and Technical Information of China (English)

    刘文宇; 朱晓斐; 戚中田

    2011-01-01

    Most of the recent biodefense work has been focused on developing DNA vaccines,which are safe to both human and environment and cost-effective,and delivery of the combined DNA vaccines can offer the potential for multiple protection.Consequently,the DNA vaccines have good prospects for research,development and applications,but their immunogenicity and delivery methods remain to be improved.This review summarizes the research status of the DNA vaccines against several biodefense pathogens listed on both the NIH priority pathogen and CDC bioterrorism registries:Bacillus anthracis,Ebola and Marburg viruses,monkeypox virus,smallpox virus,and Venezuelan equine encephalitis virus.%近年的生物防御疫苗研究集中于DNA疫苗.DNA疫苗对人以及环境相对安全、经济,并且多价联合DNA疫苗还可以提供多重保护,因此有良好的研发前景和潜在的实用价值,但也存在免疫原性不强和接种方式有待改进等问题.此文就炭疽杆菌、埃博拉病毒、马尔堡病毒、猴痘病毒、天花病毒和委内瑞拉马脑炎病毒等几种被美国NIH和CDC列为重要生物战剂的DNA疫苗研发现状作一综述.

  19. Existing antibacterial vaccines.

    Science.gov (United States)

    Mendoza, Natalia; Ravanfar, Parisa; Satyaprakash, Anita; Satyaprakah, Anita; Pillai, Sivaprabha; Creed, Rosella

    2009-01-01

    There are countless bacterial pathogens that cause disease in humans. Many of these bacterial infections not only cause significant morbidity and mortality in the human population but also cause a significant economic impact on society. Vaccines allow for reduction and potential eradication of such diseases. This article will review the currently approved antibacterial vaccines, which are vaccines for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, Haemophilus influenza, cholera, typhoid, and anthrax.

  20. Alphavirus replicon vaccines.

    Science.gov (United States)

    Vander Veen, Ryan L; Harris, D L Hank; Kamrud, Kurt I

    2012-06-01

    The alphavirus replicon technology has been utilized for many years to develop vaccines for both veterinary and human applications. Many developments have been made to the replicon platform recently, resulting in improved safety and efficacy of replicon particle (RP) vaccines. This review provides a broad overview of the replicon technology and safety features of the system and discusses the current literature on RP and replicon-based vaccines.

  1. Underutilization of Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Marshall K. Cheney

    2013-04-01

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

  2. Vaccines for Drug Abuse

    Science.gov (United States)

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  3. Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

    Science.gov (United States)

    Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

    1999-04-01

    Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

  4. Developing vaccines against pandemic influenza.

    OpenAIRE

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illust...

  5. Vaccines, our shared responsibility.

    Science.gov (United States)

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

    2015-05-05

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

  6. Vaccines and global health

    Science.gov (United States)

    Greenwood, Brian; Salisbury, David; Hill, Adrian V. S.

    2011-01-01

    Vaccines have made a major contribution to global health in recent decades but they could do much more. In November 2011, a Royal Society discussion meeting, ‘New vaccines for global health’, was held in London to discuss the past contribution of vaccines to global health and to consider what more could be expected in the future. Papers presented at the meeting reviewed recent successes in the deployment of vaccines against major infections of childhood and the challenges faced in developing vaccines against some of the world's remaining major infectious diseases such as human immunodeficiency virus (HIV), malaria and tuberculosis. The important contribution that development of more effective veterinary vaccines could make to global health was also addressed. Some of the social and financial challenges to the development and deployment of new vaccines were reviewed. The latter issues were also discussed at a subsequent satellite meeting, ‘Accelerating vaccine development’, held at the Kavli Royal Society International Centre. Delegates at this meeting considered challenges to the more rapid development and deployment of both human and veterinary vaccines and how these might be addressed. Papers based on presentations at the discussion meeting and a summary of the main conclusions of the satellite meeting are included in this issue of Philosophical Transactions of the Royal Society B. PMID:21893534

  7. Dengue virus vaccine development.

    Science.gov (United States)

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.

  8. Designing HER2 vaccines.

    Science.gov (United States)

    Foy, Teresa M; Fanger, Gary R; Hand, Susan; Gerard, Catherine; Bruck, Claudine; Cheever, Martin A

    2002-06-01

    HER2/neu is a compelling cancer vaccine candidate because it is overexpressed on some cancer cells relative to normal tissues, it is known to be immunogenic in both animal models and in humans, and it is already known to be targetable by the antibody component of the immune system in the form of monoclonal antibody therapy with trastuzumab. Vaccines offer the theoretical advantage of being able to elicit T-cell responses in addition to antibody responses. HER2 vaccines have been shown to provide benefit in animal models and to be immunogenic in humans. However, the optimal vaccine formulation is not yet known and the therapeutic efficacy of the vaccines in humans has not yet been evaluated. HER2 vaccine approaches currently being tested include peptide-based, DNA plasmid-based, and protein-based vaccines. Our group has developed and started testing a protein-based vaccine composed of both the extracellular domain of HER2 and the carboxyl terminal autophosphorylation portion of the intracellular domain. The extracellular domain was retained to provide for antibody targeting. The kinase domain of the intracellular domain was excluded because of its high degree of homology to other human kinases. The carboxyl terminal autophosphorylation domain was retained because it is the most unique and possibly most immunogenic portion of the HER2 molecule with the least homology to other members of the HER family. The vaccine, termed dHER2, is immunogenic in mice and primates. In animal models it can elicit CD8 and CD4 T-cell responses as well as antibody responses that suppress the growth of HER2-positive cancer cells in vitro and in vivo. Vaccine trials are contemplated in patients with breast cancer that will determine whether the vaccine construct is similarly immunogenic in humans.

  9. Clinical development of Ebola vaccines.

    Science.gov (United States)

    Sridhar, Saranya

    2015-09-01

    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.

  10. Your child's first vaccines

    Science.gov (United States)

    ... has ever had a severe reaction after any vaccination. A child who has a severe (life-threatening) allergy to ... in 1,000); fever over 105°F (1 child in 16,000). Serious Problems: ... These reports are extremely rare. Pneumococcal Vaccine Mild ...

  11. Conscientious Objection to Vaccination.

    Science.gov (United States)

    Clarke, Steve; Giubilini, Alberto; Walker, Mary Jean

    2017-03-01

    Vaccine refusal occurs for a variety of reasons. In this article we examine vaccine refusals that are made on conscientious grounds; that is, for religious, moral, or philosophical reasons. We focus on two questions: first, whether people should be entitled to conscientiously object to vaccination against contagious diseases (either for themselves or for their children); second, if so, to what constraints or requirements should conscientious objection (CO) to vaccination be subject. To address these questions, we consider an analogy between CO to vaccination and CO to military service. We argue that conscientious objectors to vaccination should make an appropriate contribution to society in lieu of being vaccinated. The contribution to be made will depend on the severity of the relevant disease(s), its morbidity, and also the likelihood that vaccine refusal will lead to harm. In particular, the contribution required will depend on whether the rate of CO in a given population threatens herd immunity to the disease in question: for severe or highly contagious diseases, if the population rate of CO becomes high enough to threaten herd immunity, the requirements for CO could become so onerous that CO, though in principle permissible, would be de facto impermissible.

  12. Towards universal influenza vaccines?

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); G.F. Rimmelzwaan (Guus)

    2011-01-01

    textabstractVaccination is the most cost-effective way to reduce the considerable disease burden of seasonal influenza. Although seasonal influenza vaccines are effective, their performance in the elderly and immunocompromised individuals would benefit from improvement. Major problems related to the

  13. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

  14. Vaccines and autoimmunity.

    Science.gov (United States)

    Agmon-Levin, Nancy; Paz, Ziv; Israeli, Eitan; Shoenfeld, Yehuda

    2009-11-01

    Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.

  15. Pricing of new vaccines.

    Science.gov (United States)

    Lee, Bruce Y; McGlone, Sarah M

    2010-08-01

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

  16. Vaccines and autoimmunity.

    Science.gov (United States)

    De Martino, M; Chiappini, E; Galli, L

    2013-01-01

    Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

  17. [Influenza vaccine and adjuvant].

    Science.gov (United States)

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.

  18. Against vaccine assay secrecy.

    Science.gov (United States)

    Herder, Matthew; Hatchette, Todd F; Halperin, Scott A; Langley, Joanne M

    2015-01-01

    Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canada's access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors.

  19. Against vaccine assay secrecy

    Science.gov (United States)

    Herder, Matthew; Hatchette, Todd F; Halperin, Scott A; Langley, Joanne M

    2015-01-01

    Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canada's access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors. PMID:25826194

  20. Vaccines and multiple sclerosis

    DEFF Research Database (Denmark)

    Mailand, Mia Topsøe; Frederiksen, Jette Lautrup

    2017-01-01

    Vaccinations are often the most effective tool against some disease known to mankind. This study offers a literature review on the role of vaccines regarding the risk of developing multiple sclerosis (MS) and MS relapse. The method used in this study is a systematic literature review...... on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles-mumps-rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...... was found for influenza. Further research is needed for the potential therapeutic use of the BCG vaccine in patients in risk of developing MS and for the preventive potential of the tetanus and diphtheria vaccine....

  1. Vaccine-Hesitant Justifications

    Science.gov (United States)

    Rodriguez, Nathan J.

    2016-01-01

    Vaccine-preventable diseases have re-emerged as more individuals have strayed from the recommended inoculation schedule. Previous work on vaccine hesitancy is generally limited to content analyses. Using grounded theory, this project examines vaccine debates on a prominent discussion board over a period of five years. Individuals generally justified opposition or hesitancy toward vaccines through personal experience and/or research, and the concepts of narrative persuasion and the conflation of expertise help describe the most prominent characteristics of such discourse. A consideration of online comments regarding vaccinations allows practitioners to not only become better prepared for patient concerns they might encounter, and but also become more familiar with the types of anecdotes and narratives that may be influential but left unspoken in face-to-face conversations. PMID:28508015

  2. Diseases and vaccines

    DEFF Research Database (Denmark)

    Andersen, Nina Blom; Almlund, Pernille

    2012-01-01

    between authorities, politicians, media and citizens. On the contrary, no broad commitment about the offer of a new pandemic vaccine to individuals from e.g. at-risk groups was reached. The vaccine was characterized by considerable uncertainty with regard to effects and side effects and many people...... considered the vaccine as risky and a threat more severe than the influenza. The health authorities? communication was more unclear on this question, confusion increased in the Danish population and more critical voices were raised. This uncertain communication about the vaccines? effects and side effects...... and the critical voices in the population are widespread in communication about vaccines in general and an increasing number of people are expressing skepticism and deselect this product. The communication processes are seen as a typical example of the difficulties of communicating science and risk and show how...

  3. Next generation vaccines.

    Science.gov (United States)

    Riedmann, Eva M

    2011-07-01

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

  4. Neisseria meningitidis B vaccines.

    Science.gov (United States)

    Panatto, Donatella; Amicizia, Daniela; Lai, Piero Luigi; Gasparini, Roberto

    2011-09-01

    Invasive infections caused by Neisseria meningitidis are a serious public health problem worldwide and have a heavy economic impact. The incidence of invasive disease due to Neisseria meningitidis is highly variable according to geographical area and serogroup distribution. Since the introduction of vaccination programs with conjugated vaccine C in children and adolescents, most cases of invasive meningococcal disease in developed countries have been caused by meningococcus B. It is important to underline that invasive meningococcal disease will not be controlled until safe and effective vaccines for meningococcal B are available and widely used. The aims of this article are to describe the most recent developments in meningococcal B vaccines and to discuss how these vaccines can contribute to containing meningococcal disease.

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

    Science.gov (United States)

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

    2014-09-22

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

  6. 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

  7. Smallpox Antiviral Drug

    Science.gov (United States)

    2007-01-01

    strategies is essential. ACKNOWLEDGMENTS We thank Robert Jordan, Sean Amberg, and Tove’ Bolken for critical reviews of the manuscript. REFERENCES...part II. Adverse events. Clin Infect Dis 37:251–271. Ghosn J, Chaix ML, Peytavin G, Rey E, Bresson JL, Goujard C, Katlama C, Viard JP, Treluyer JM

  8. Parental knowledge of paediatric vaccination

    Directory of Open Access Journals (Sweden)

    Borràs Eva

    2009-05-01

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

  9. [Present status of vaccines in 1989].

    Science.gov (United States)

    Roussey, M; Dabadie, A

    1989-01-01

    The authors describe 2 new vaccines now available in France: one is the GenHevac, an hepatitis B vaccine, the first virus recombinant vaccine; the other one is the Typhim Vi, a polysaccharide typhoid vaccine. Three other vaccines are currently used in foreign countries and will be soon available: the Hemophilus influenzae vaccine, the acellular pertussis vaccine and the varicella vaccine. Rotavirus and Cytomegalovirus vaccines are studied for their clinical efficacy.

  10. Technical Transformation of Biodefense Vaccines

    Science.gov (United States)

    Lu, Shan; Wang, Shixia

    2013-01-01

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

  11. DNA vaccine: the miniature miracle

    Directory of Open Access Journals (Sweden)

    Karthik Kaliaperumal

    2013-08-01

    Full Text Available DNA, the essential part of the life is making way in to new vaccine technology. Plasmid vectors from the bacteria have revolutionized the world of vaccine design by its new technology – DNA vaccines. Small portion of the nucleotides from the pathogen held under the control of promoter in a plasmid vector can be used as a vaccine. DNA vaccines alleviate the odds of the other vaccines by having good hold on both the faces of the immunity. The key to the success of DNA vaccine lies in the route of administration of the vaccine which can be done in many ways. Prime boost strategy is an approach used to boost the action of DNA vaccine. To date there are only four DNA vaccine available in the market. [Vet World 2013; 6(4.000: 228-232

  12. Priorities for the national vaccine plan

    National Research Council Canada - National Science Library

    Committee on Review of Priorities in the National Vaccine Plan; Institute of Medicine

    .... Priorities for the National Vaccine Plan examines the extraordinarily complex vaccine enterprise, from research and development of new vaccines to financing and reimbursement of immunization services...

  13. Flu vaccination in pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Siettou

    2012-04-01

    Full Text Available In periods of seasonal influenza, during pandemic flu in the past and from recent experience that we have the emergence of influenza A (H1N1, pregnant compared with non-pregnant women are at increased risk to get sick and to develop serious complications up to mortality. Purpose: This paper examines the risks that arise for pregnant from contamination with the flu virus and the safety of influenza vaccination in pregnancy. Method: The method involves searching review and research studies in Pubmed data base mainly of the 2000 until 2009 and the words were used is pregnancy, flu vaccination, complications of the flu vaccination at the period of pregnancy. Results: Morbidity during periods of seasonal influenza in pregnant women is increased, while in times of pandemic are recorded fatalities. Based on this, specific recommendations have been made for a flu vaccination in pregnant women, both from the CDC, the American College of Obstetricians and Gynecologists in the U.S. and other official bodies like the World Health Organization, according to that the constitution of influenza vaccine in the pregnancy is necessary, given that the probability of morbidity in this period is increased at 10%. Conclusions: The studies so far to influenza vaccination in pregnancy, do not record serious complications for pregnant women and infants. However more research needs to be done on the safety of influenza vaccination in pregnancy.

  14. Early life vaccination

    DEFF Research Database (Denmark)

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

    2016-01-01

    the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

  15. Alphavirus-Based Vaccines.

    Science.gov (United States)

    Lundstrom, Kenneth

    2016-01-01

    Alphavirus vectors based on Semliki Forest virus, Sindbis virus, and Venezuelan equine encephalitis virus have been widely applied for vaccine development. Naked RNA replicons, recombinant viral particles, and layered DNA vectors have been subjected to immunization in preclinical animal models with antigens for viral targets and tumor antigens. Moreover, a limited number of clinical trials have been conducted in humans. Vaccination with alphavirus vectors has demonstrated efficient immune responses and has showed protection against challenges with lethal doses of virus and tumor cells, respectively. Moreover, vaccines have been developed against alphaviruses causing epidemics such as Chikungunya virus.

  16. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

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

  17. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

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

  18. Research toward Malaria Vaccines

    Science.gov (United States)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  19. Anti-addiction vaccines

    Science.gov (United States)

    Shen, Xiaoyun; Orson, Frank M.

    2011-01-01

    Despite intensive efforts to eradicate it, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Anti-addiction vaccines can produce the antibodies to block the effects of these drugs on the brain, and have great potential to ameliorate the morbidity and mortality associated with illicit drug intoxications. This review provides a current overview of anti-addiction vaccines that are under clinical trial and pre-clinical research evaluation. It also outlines the development challenges, ethical concerns, and likely future intervention for anti-addiction vaccines. PMID:22003367

  20. Meningococcal vaccine evolution

    Directory of Open Access Journals (Sweden)

    Gianni Bona

    2012-06-01

    Full Text Available Neisseria meningitidis is a leading cause of bacterial sepsis and meningitis worldwide. Although polysaccharide and glycoconjugate vaccines have been developed for serogroups A, C, Y and W-135, currently there are no broadly effective vaccines available for the prevention of meningococcal B disease. A general overview of the burden of the disease and the strains prevalence in the world with the focus in particular on the Italian situation is provided in this article, together with the vaccinations developed and under evaluation.

  1. Immunodominant viral peptides as determinants of cross-reactivity in the immune system--Can we develop wide spectrum viral vaccines?

    Science.gov (United States)

    Vieira, G F; Chies, J A B

    2005-01-01

    When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system

  2. DNA vaccines and intradermal vaccination by DNA tattooing.

    Science.gov (United States)

    Oosterhuis, K; van den Berg, J H; Schumacher, T N; Haanen, J B A G

    2012-01-01

    Over the past two decades, DNA vaccination has been developed as a method for the induction of immune responses. However, in spite of high expectations based on their efficacy in preclinical models, immunogenicity of first generation DNA vaccines in clinical trials was shown to be poor, and no DNA vaccines have yet been licensed for human use. In recent years significant progress has been made in the development of second generation DNA vaccines and DNA vaccine delivery methods. Here we review the key characteristics of DNA vaccines as compared to other vaccine platforms, and recent insights into the prerequisites for induction of immune responses by DNA vaccines will be discussed. We illustrate the development of second generation DNA vaccines with the description of DNA tattooing as a novel DNA delivery method. This technique has shown great promise both in a small animal model and in non-human primates and is currently under clinical evaluation.

  3. Vaccine safety controversies and the future of vaccination programs.

    Science.gov (United States)

    François, Guido; Duclos, Philippe; Margolis, Harold; Lavanchy, Daniel; Siegrist, Claire-Anne; Meheus, André; Lambert, Paul-Henri; Emiroğlu, Nedret; Badur, Selim; Van Damme, Pierre

    2005-11-01

    In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

  4. EXPERIMENTAL MEASLES VACCINES: A RESEARCH TOOL IN VACCINATION EVENTS

    Directory of Open Access Journals (Sweden)

    V. A. Liashenko

    2007-01-01

    Full Text Available Abstract. The review article considers different variants of measles vaccine that may be classified into two groups, i.e., vaccines that do not contain viable measles virus, and attenuated measles vaccines which could be employed in unusual manner.The first group includes DNA-vaccines, recombinant vaccine strains encoding synthesis of measles hemagglutinin and fusion protein, as well as peptide vaccines containing molecular fragments of these proteins. The mentioned variants of vaccines were effective in animal experiments, but they have not been tested in humans. The second group includes live attenuated mucosal measles vaccins applied in combination with immunomodulator(s, as aerosol and intranasally. Efficiency of these vaccines was tested and confirmed by immunization of children and adults. Mucosal measles vaccine induces local production of IgA measles antibodies, along with induced synthesis of circulating IgM and IgG antibodies against measles. The latter experimental variant could be a live attenuated measles vaccine containing some immunity-modulating agent. Elaboration of these variant was based on the known data about transient immunosuppressive activity of measles vaccine. An appropriate experimental variant represents a mixture of attenuated measles vaccine and synthetic immunomodulating agent (MP-2 peptide which protects T-lymphocytes from inhibitory effect of the measles virus. In present revue, some data are presented concerning the mechanisms of immunogenic activity and adverse effects of measles vaccines.

  5. Veterinary vaccines against toxoplasmosis.

    Science.gov (United States)

    Hiszczyńska-Sawicka, Elżbieta; Gatkowska, Justyna M; Grzybowski, Marcin M; Długońska, Henryka

    2014-09-01

    Toxoplasma gondii is a cosmopolitan protozoan parasite that infects a wide range of mammal and bird species. Common infection leads to high economic (e.g., abortions in sheep) and human (e.g., congenital toxoplasmosis or neurotoxoplasmosis in humans) losses. With one exception (Toxovax for sheep), there are no vaccines to prevent human or animal toxoplasmosis. The paper presents the current state and challenges in the development of a vaccine against toxoplasmosis, designed for farm animals either bred for consumption or commonly kept on farms and involved in parasite transmission. So far, the trials have mostly revolved around conventional vaccines and, compared with the research using laboratory animals (mainly mice), they have not been very numerous. However, the results obtained are promising and could be a good starting point for developing an effective vaccine to prevent toxoplasmosis.

  6. Ingredients of Vaccines

    Science.gov (United States)

    ... quantities of mercury, aluminum, formaldehyde, human serum albumin, antibiotics, and yeast proteins in vaccines have not been found to be harmful in humans or experimental animals... Top of Page Related Pages Common Questions about ...

  7. [Development of new vaccines].

    Science.gov (United States)

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

    Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.

  8. Antibacterials: A sweet vaccine

    Science.gov (United States)

    Bundle, David

    2016-03-01

    Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.

  9. Childhood Vaccine Schedule

    Science.gov (United States)

    ... the MMR and Varicella vaccines at the same time. Now it does not express a preference for giving them separately or at the same time. Protects against chickenpox, a usually mild infectious disease ...

  10. Hepatitis B Vaccination Protection

    Science.gov (United States)

    Fact Sheet Hepatitis B Vaccination Protection Hepatitis B virus (HBV) is a pathogenic microorganism that can cause potentially life- threatening disease in humans. HBV infection is transmitted through exposure ...

  11. Vaccines against typhoid fever.

    Science.gov (United States)

    Guzman, Carlos A; Borsutzky, Stefan; Griot-Wenk, Monika; Metcalfe, Ian C; Pearman, Jon; Collioud, Andre; Favre, Didier; Dietrich, Guido

    2006-05-01

    Because of high infectivity and significant disease burden, typhoid fever constitutes a major global health problem. Implementation of adequate food handling practices and establishment of safe water supplies are the cornerstone for the development of an effective prevention program. However, vaccination against typhoid fever remains an essential tool for the effective management of this disease. Currently, there are two well tolerated and effective licensed vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen and can be administered either intramuscularly or subcutaneously and the other is based on the use of live attenuated bacteria for oral administration. The advantages and disadvantages of the various approaches taken in the development of a vaccine against typhoid fever are discussed, along with the potential for future vaccine candidates.

  12. Tuberculosis vaccine types and timings.

    Science.gov (United States)

    Orme, Ian M

    2015-03-01

    Traditionally, the design of new vaccines directed against Mycobacterium tuberculosis, the most successful bacterial pathogen on the planet, has focused on prophylactic candidates that would be given to individuals while they are still young. It is becoming more apparent, however, that there are several types of vaccine candidates now under development that could be used under various conditions. Thus, in addition to prophylactic vaccines, such as recombinant Mycobacterium bovis BCG or BCG-boosting vaccines, other applications include vaccines that could prevent infection, vaccines that could be given in emergency situations as postexposure vaccines, vaccines that could be used to facilitate chemotherapy, and vaccines that could be used to reduce or prevent relapse and reactivation disease. These approaches are discussed here, including the type of immunity we are trying to specifically target, as well as the limitations of these approaches.

  13. Current status of rotavirus vaccines

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    Background: 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. Data sources: 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. Results: 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. Conclusions: 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.

  14. Vaccines against cysticercosis.

    Science.gov (United States)

    Sciutto, Edda; Fragoso, Gladis; de Aluja, Aline S; Hernández, Marisela; Rosas, Gabriela; Larralde, Carlos

    2008-01-01

    Taenia solium cysticercosis is a major parasitic disease that seriously and frequently affects human health and economy in undeveloped countries. Since pigs are an indispensable intermediate host, it is conceivable to curb transmission by reducing pig cysticercosis through their effective vaccination. This article reviews current knowledge on the development vaccines against porcine cysticercosis. It highlights the development of several versions of S3Pvac aimed to increase effectiveness, reduce costs and increase feasibility by novel delivery systems and alternative routes of administration.

  15. Epilepsy and vaccinations: Italian guidelines.

    Science.gov (United States)

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

    2013-10-01

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

  16. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

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

  17. Military Infectious Diseases Update on Vaccine Development

    Science.gov (United States)

    2011-01-24

    development thrusts • Enterotoxigenic Escherichia coli (ETEC) vaccines • Shigella vaccines • Campylobacter jejuni vaccines 2011 MHS Conference Vaccines...Injectisome extending from Shigella Injectisome Injectisome graphic 2011 MHS Conference  Campylobacter jejuni – Transmission: Foodborne – Inoculum

  18. Understanding Thimerosal, Mercury, and Vaccine Safety

    Science.gov (United States)

    ... fungus. It is used as a preservative for flu vaccines in multi-dose vials, to keep the vaccine ... as much as possible. • Today, except for some flu vaccines in multi-dose vials, no recommended childhood vaccines ...

  19. Vaccinations for Adults with HIV Infection

    Science.gov (United States)

    Vaccinations for Adults with HIV Infection The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  20. Vaccinations for Adults with Hepatitis C Infection

    Science.gov (United States)

    Vaccinations for Adults with Hepatitis C Infection This table shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...