12/25/2023 0 Comments Us smallpox vaccine stockpileThese vaccines induced robust humoral immunity characterized by high antibody titers capable of neutralizing and opsonizing viral particles, fixing complement, hemagglutination, as well as participating in antibody dependent cell cytotoxicity. Several recent studies have demonstrated that these live vaccines can be diluted 5–10-fold with no significant decreases in immunogenicity. Historically the development of this ‘take’ was considered evidence of protection. Successful administration of the vaccine typically led to the development of a characteristic pustule at the vaccination site. Vaccines used during the eradication effort (Dryvax ®, APSV ®, Lancy–Vaxina ®, L-IVP ®) are termed first-generation vaccines (last produced in the 1970s and early 1980s) and contained live vaccinia virus administered by puncturing the skin of the upper arm with a bifurcated needle ( Table 1 In this review we will focus on the highlights of research regarding the mechanisms of disease protection elicited by smallpox vaccines. Faced with inadequate stocks of smallpox vaccine, an outdated vaccine production method, an increasing unvaccinated, and hence susceptible population, as well as a growing number of both immunosuppressed individuals and people with vaccine contraindications (heart conditions, cancer patients, organ transplant recipients, skin diseases such as eczema) research efforts focused on increasing our understanding of poxvirus immunity in order to develop safe and effective next-generation vaccines. Terrorist activities in the early 21st century as well as imported outbreaks of monkeypox in the USA spurred renewed interest in biodefense countermeasures for these public health threats. These are (1) serum neutralizing antibody titer > 1:32 and (2) the formation of a ‘take’ or vesicle at the vaccination site due to cellular immune responses to the local infection. In fact, there are two historical definitions of ‘protection’ that, while not mutually exclusive, do rely on humoral and cellular immune responses, respectively. During the height of the eradication effort in the 1960s research efforts focused on humoral immunity, although the importance of cellular responses was predicted. Rare, but potentially life-threatening adverse events, led to the cessation of vaccine use among the general public, and recent vaccination programs have highlighted the risk of cardiovascular adverse events. In spite of its indefinite origins vaccinia virus was the basis for extremely effective vaccines that, together with surveillance and monitoring led to the eradication of smallpox in 1980. Vaccination quickly became widespread and by the 20th century almost all vaccines contained yet another orthopoxvirus: vaccinia virus (VACV). Early practitioners used a wide variety of pox viruses taken from or grown on cows, sheep, horses, goats, pigs, and buffaloes. In 1798 Edward Jenner advanced the concept of using cowpox as a prophylactic agent against smallpox. Variola virus, the causative agent of smallpox, can be found throughout human history and probably developed alongside human civilization. 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. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. 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. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. 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.
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