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Vaccinia virus (VACV) is a large, complex, enveloped double-stranded DNA virus belonging to the Orthopoxvirus genus of the Poxviridae family (Moss, 2013). It is most notably recognized as the active constituent of the live-virus vaccine that led to the global eradication of smallpox and remains the primary platform for preventing mpox and other orthopoxvirus infections (CDC, 2024). As an immunological target, VACV elicits a multifaceted response where neutralizing antibodies primarily target surface proteins of the mature virion (MV), such as L1 and A27, and the extracellular enveloped virion (EV), such as B5 and A33, while T cells recognize a broad array of internal structural and non-structural proteins (He et al., 2007). In therapeutic development, VACV is the target of antiviral agents like tecovirimat, which inhibits the VP37 protein (encoded by the F13L gene) to block viral egress, and brincidofovir, which targets the viral DNA polymerase (FDA, 2018; FDA, 2021). Beyond its role in infectious disease, VACV serves as a versatile tool in biotechnology, acting as a vector for recombinant vaccines and an oncolytic platform for cancer immunotherapy (Guo et al., 2019).
Inhibition of viral egress via VP37 (tecovirimat); inhibition of viral DNA polymerase (brincidofovir, cidofovir); passive immunization (Vaccinia Immune Globulin); active immunization (ACAM2000, JYNNEOS).
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