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The Journal of Allergy and Clinical... Dec 2006The global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. Routine vaccination of the general population... (Review)
Review
The global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. Routine vaccination of the general population is no longer recommended. However, stocks of variola virus, the causative agent of smallpox, still exist in 2 secure laboratories, and permanent disposal has been controversial. In addition, there is speculation that variola virus may exist outside of these 2 facilities, and there is a concern that the threat of smallpox will be used as a bioterrorist weapon. In 2002, this concern led to a vaccination campaign in US military and civilian healthcare workers and first responders. Although the historical live virus vaccine has proven efficacy, it also is associated with serious adverse events and rare fatal reactions, particularly in the setting of immunodeficiency and atopic eczema. In addition, this vaccine was historically produced using animal intermediaries in a process that was prone to contamination and not acceptable for current manufacturing standards. Development of alternative poxvirus vaccines is focused on replication-defective viruses, gene-based vectors, and subunit approaches to improve safety and immunogenicity. The conundrum is that in the absence of an intentional release of variola, efficacy evaluation of new candidate vaccines will be limited to animal model testing, which creates new challenges for the vaccine licensure process. Although motivated by the threat of bioterrorism, the hope is for new poxvirus vaccines to have their greatest utility against other pathogenic orthopoxviruses such as monkeypox and for the development of recombinant poxvirus-based vectors to treat and prevent other diseases.
Topics: Animals; Bioterrorism; Clinical Trials as Topic; Dermatitis, Atopic; Humans; Immunologic Deficiency Syndromes; Monkey Diseases; Orthopoxvirus; Poxviridae; Poxviridae Infections; Smallpox; Smallpox Vaccine; Vaccination; Vaccines, Attenuated; Vaccines, Synthetic; Viral Vaccines; Virus Replication
PubMed: 17157663
DOI: 10.1016/j.jaci.2006.09.037 -
Swiss Medical Weekly Jul 2008To assess clinical reactions, immune responses and adverse events to undiluted, three- and sixfold diluted Lister strain vaccine stockpiled in Switzerland. (Randomized Controlled Trial)
Randomized Controlled Trial
QUESTION UNDER STUDY
To assess clinical reactions, immune responses and adverse events to undiluted, three- and sixfold diluted Lister strain vaccine stockpiled in Switzerland.
METHODS
A prospective, triple-blinded, randomised, parallel group clinical trial was performed.
RESULTS
From 2001 to 2007 104 persons with an indication for vaccinia vaccination were recruited. They had a median age of 33 years (range 18-65), 56 (53.8%) were re-vaccinees and 48 (46.2%) primary vaccinees. There was no statistically significant variation in the proportion of revaccinees between diluted and undiluted vaccine groups (75% vs 51%, p = 0.118). With an overall clinical take rate (major reaction) of 97.1% the majority of the vaccinia-naïve participants exhibited an at least fourfold increase of neutralising antibody titres (32/38, 84.2%) post-vaccination. Interestingly this proportion was lower among re-vaccinees (29/46, 63.0%, p = 0.048). No significant difference was observed in the take rate or at least fourfold seroconversion rate between the threefold and sixfold diluted vaccine doses. Adverse events were reported by 98 (94.2%) participants, not accounting for itching at the vaccination site.
CONCLUSION
Subjects requiring immunisation were successfully (re-) vaccinated with undiluted as well as with three- or sixfold diluted vaccinia vaccine. Our findings complement previous studies with respect to the clinical take rate and immune response. The rate of adverse events was substantial but not unexpected and no severe adverse events occurred. In conclusion, the existing smallpox vaccine stockpile might be expanded by administering three- or sixfold diluted vaccine doses combined with a careful pre-vaccination screening and extensive instructions to vaccinees.
Topics: Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Female; Humans; Immunization, Secondary; Male; Middle Aged; Smallpox Vaccine; Vaccinia virus
PubMed: 18654870
DOI: 10.4414/smw.2008.11966 -
Vaccine Dec 2017For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was... (Review)
Review
Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine.
For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. A favorite candidate for a vaccinia ancestor has been the horsepox virus. Edward Jenner himself suspected that cowpox derived from horsepox and he also believed that "matter" obtained from either disease could be used as preventative of smallpox. During the 19th century, inoculation with cowpox (vaccination) was used in Europe alongside with inoculation with horsepox (equination) to prevent smallpox. Vaccine-manufacturing practices during the 19th century may have resulted in the use of virus mixtures, leading to different genetic modifications that resulted in present-day vaccinia strains. Horsepox, a disease previously reported only in Europe, has been disappearing on that continent since the beginning of the 20th century and now seems to have become extinct, although the virus perhaps remains circulating in an unknown reservoir. Genomic sequencing of a horsepox virus isolated in Mongolia in 1976 indicated that, while closely related to vaccinia, this horsepox virus contained additional, potentially ancestral sequences absent in vaccinia. Recent genetic analyses of extant vaccinia viruses have revealed that some strains contain ancestral horsepox virus genes or are phylogenetically related to horsepox virus. We have recently reported that a commercially produced smallpox vaccine, manufactured in the United States in 1902, is genetically highly similar to horsepox virus, providing a missing link in this 200-year-old mystery.
Topics: Animals; Cowpox; Genome, Viral; High-Throughput Nucleotide Sequencing; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Orthopoxvirus; Phylogeny; Smallpox; Smallpox Vaccine; Vaccination; Vaccinia virus; Variola virus
PubMed: 29137821
DOI: 10.1016/j.vaccine.2017.11.003 -
Vaccine Nov 2015LC16m8 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... (Review)
Review
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.
Topics: Adult; Animals; Antibodies, Viral; Bioterrorism; Cell Culture Techniques; Clinical Trials as Topic; Disease Models, Animal; Humans; Japan; Mice; Mpox (monkeypox); Smallpox; Smallpox Vaccine; Strategic Stockpile; Vaccines, Attenuated; Vaccinia virus
PubMed: 26319072
DOI: 10.1016/j.vaccine.2015.07.111 -
The Lancet. Infectious Diseases Jan 2004Human monkeypox is a rare viral zoonosis endemic to central and western Africa that has recently emerged in the USA. Laboratory diagnosis is important because the virus... (Comparative Study)
Comparative Study Review
Human monkeypox is a rare viral zoonosis endemic to central and western Africa that has recently emerged in the USA. Laboratory diagnosis is important because the virus can cause disease that is clinically indistinguishable from other pox-like illnesses, particularly smallpox and chickenpox. Although the natural animal reservoir of the monkeypox virus is unknown, rodents are the probable source of its introduction into the USA. A clear understanding of the virulence and transmissibility of human monkeypox has been limited by inconsistencies in epidemiological investigations. Monkeypox is the most important orthopoxvirus infection in human beings since the eradication of smallpox in the 1970s. There is currently no proven treatment for human monkeypox, and questions about its potential as an agent of bioterrorism persist.
Topics: Adult; Africa; Animals; Bioterrorism; Child; Diagnosis, Differential; Disease Outbreaks; Disease Reservoirs; Dogs; Exanthema; Humans; Mpox (monkeypox); Monkeypox virus; Population Surveillance; Rabbits; Rats; Rodentia; Sciuridae; Smallpox Vaccine; United States
PubMed: 14720564
DOI: 10.1016/s1473-3099(03)00856-9 -
American Journal of Transplantation :... Jul 2003Recent bioterrorism raises the specter of reemergence of smallpox as a clinical entity. The mortality of variola major infection ('typical smallpox') was approximately... (Review)
Review
Recent bioterrorism raises the specter of reemergence of smallpox as a clinical entity. The mortality of variola major infection ('typical smallpox') was approximately 30% in past outbreaks. Programs for smallpox immunization for healthcare workers have been proposed. Atypical forms of smallpox presenting with flat or hemorrhagic skin lesions are most common in individuals with immune deficits with historic mortality approaching 100%. Smallpox vaccination, even after exposure, is highly effective. Smallpox vaccine contains a highly immunogenic live virus, vaccinia. Few data exist for the impact of variola or safety of vaccinia in immunocompromised hosts. Both disseminated infection by vaccinia and person-to-person spread after vaccination are uncommon. When it occurs, secondary vaccinia has usually affected individuals with pre-existing skin conditions (atopic dermatitis or eczema) or with other underlying immune deficits. Historically, disseminated vaccinia infection was uncommon but often fatal even in the absence of the most severe form of disease, "progressive vaccinia". Some responded to vaccinia immune globulin. Smallpox exposure would be likely to cause significant mortality among immunocompromised hosts. In the absence of documented smallpox exposures, immunocompromised hosts should not be vaccinated against smallpox. Planning for bioterrorist events must include consideration of uniquely susceptible hosts.
Topics: Bioterrorism; Cross Infection; Humans; Immune System Diseases; Smallpox; Smallpox Vaccine; Transplantation; Vaccinia virus
PubMed: 12814470
DOI: 10.1034/j.1600-6143.2003.00145.x -
Vaccine Jun 2016Smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. Smallpox vaccine efficacy was historically...
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.
Topics: Adult; Antibodies, Neutralizing; Antibodies, Viral; Cytokines; Female; Gene Expression; Humans; Immunity, Cellular; Immunity, Humoral; Immunity, Innate; Immunogenicity, Vaccine; Male; Neutralization Tests; Smallpox; Smallpox Vaccine; Vaccines, Attenuated; Young Adult
PubMed: 27177944
DOI: 10.1016/j.vaccine.2016.05.005 -
Public Health Reports (Washington, D.C.... 1980
Topics: Communicable Disease Control; Humans; Population Surveillance; Smallpox; Smallpox Vaccine; World Health Organization
PubMed: 7422808
DOI: No ID Found -
BMJ (Clinical Research Ed.) Oct 1990
Topics: History, 18th Century; History, 19th Century; History, 20th Century; History, Modern 1601-; Humans; Medicine in the Arts; Research; Scurvy; Smallpox Vaccine; United Kingdom
PubMed: 2224257
DOI: 10.1136/bmj.301.6754.763 -
Biomedica : Revista Del Instituto... May 2020Introduction: The social history of written culture reflects the reading and writing habits and practices that allow us to appropriate the texts to build our sense of...
With regard to the bicentennial of the independence of Colombia: Reading practices of Antonio Nariño and the development of a presumably effective vaccine against smallpox.
Introduction: The social history of written culture reflects the reading and writing habits and practices that allow us to appropriate the texts to build our sense of community. Hence, the library of individuals reflects their reading habits, their way of imagining nature, their relationship with political and religious power, and their involvement with society. Objective: To interpret Antonio Nariño’s reading practices by means of the medical books in his library to approach the way he developed a presumably effective vaccine against smallpox. Materials and methods: We made a bibliographic description of the documents “Confiscación y embargo de bienes de Nariño” and “Papeles, libros y bienes de Sebastián López Ruiz en poder de Nariño” from the Nariño Archive of the Universidad Nacional de Colombia. Results: Out of the 39 books about Medicine (seven treatises on surgery, 12 compendia of practical exercise, 11 disease manuals, seven compendia of medical topics, and two books on childbirth) three were smallpox treatises. Conclusion: Antonio Nariño’s medical and scientific practice reflects his reading and writing habits, his skills and competences, and his cultural attitudes, which promoted the notion of public health. The study of Nariño as a self-taught physician allowed for relating the scientific production techniques (development of the vaccine) and the cultural materiality (state of the art) based on the medical texts in his library.
Topics: Books; Colombia; History, 19th Century; Smallpox Vaccine
PubMed: 32463602
DOI: 10.7705/biomedica.5024