Us smallpox vaccine stockpile12/15/2023 ![]() These vaccines can be used both for preexposure vaccination to prevent infection and as a postexposure strategy for individuals who experience high-risk exposure to mpox. JYNNEOS (developed by Bavarian Nordic) is a third-generation live vaccine containing the modified vaccinia Ankara (MVA) strain, which is replication defective. ![]() ACAM2000 (developed by Pasteur Biologics Company) is a second-generation vaccine that consists of a replication-competent, live vaccinia strain derived from a single clonal virus isolate from Dryvax, with reduced neurovirulence in animal models ( 13). The first-generation vaccines, e.g., Dryvax, were used in the latter phases of the smallpox eradication effort and were phased out for higher-purity, less reactogenic, and better-tolerated second-generation vaccines ( 12). There are currently two licensed smallpox vaccines in the United States. Vaccines made of vaccinia virus, an Orthopoxvirus with low virulence, were used to eradicate smallpox and have been shown to confer protection against mpox in several animal models of the disease ( 6– 11). Novel routes of virus transmission may have implications for long-term virus shedding or carriage, acquisition of other infections (e.g., HIV), and vaccine responses. Mucosal immune responses to the mpox virus are not well characterized. Mucosal transmission through sexual contact has emerged as an important mechanism of transmission and is frequently associated with recto-genital lesions in men, vaginal lesions in women, and pharyngeal lesions in both ( 3, 5), which had not been described in previous outbreaks. During the 2022 global outbreak of mpox, infections have predominantly occurred in men who have sex with men (MSM), representing 90%–95% of cases across cohorts ( 3, 4). Orthopoxviruses exhibit immunologic cross-reactivity, and immune responses to one Orthopoxvirus can confer some degree of protection from infection by other members of the genus ( 2). Mpox virus is a DNA virus belonging to the Orthopoxvirus genus and a close relative of variola, which caused the now-eradicated smallpox disease. In this Viewpoint, we discuss what is known about the effectiveness of the available vaccines, emerging data on their use and effectiveness in the current mpox outbreak, and how vaccines fit into the ambitious but more realistic goal of eliminating mpox in newly affected countries and reducing its impact on public health in endemic countries ( Figure 1). In addition, smallpox vaccines are not currently available in mpox-endemic countries in Africa. Moreover, pre- and asymptomatic transmission is a concern, and smallpox vaccines may not provide sterilizing immunity to the disease. While mpox disease is easily diagnosable, the mpox virus has a wide host range, and its reservoir has not been not fully characterized. Eradication is a much more challenging proposition and probably impossible to attain for mpox. Elimination of disease will require a reduction in the number of cases of mpox to zero in defined geographic areas, a goal that may only be feasible in newly affected, nonendemic countries. However, many unanswered questions remain about the role vaccines could play in eliminating mpox as a global threat to human health. Much of the response to the mpox outbreak has relied heavily on repurposing smallpox vaccines as tools for pre- and postexposure prevention to contain the outbreak. There has also likely been a herd effect, with nonvaccinated individuals benefiting from the interruption of transmission among vaccinated individuals. This decline in new cases can be attributed to rapid rollout of vaccines, growing herd immunity built by the rapid spread of infection in individuals considered at highest risk, and behavior modification. After an initial period of relatively rapid spread, which earned the outbreak the designation of a public health emergency of international concern (PHEIC), case numbers have steadily declined, especially in high-income countries. To date, over 80,000 cases have been reported, mostly concentrated in North America, Brazil, and Western Europe ( 1). ![]() ![]() An outbreak of monkeypox (mpox) virus emerged on the global landscape in May 2022 and rapidly spread to several nonendemic countries in every WHO health region.
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