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The Orthopoxvirus A33 protein is a 23-28 kDa type II transmembrane glycoprotein essential for the dissemination of orthopoxviruses like Variola (smallpox) and Mpox (UniProt P33835). It is specifically located on the outer membrane of the extracellular enveloped virus (EEV) and is required for the efficient wrapping of intracellular mature virus (IMV) and the subsequent formation of actin tails for cell-to-cell spread (PubMed: 11832461). Because the EEV form is crucial for systemic spread and immune evasion, A33 is a major target for protective immunity and vaccine design (PubMed: 15141014). Antibodies targeting A33 do not neutralize the IMV form but instead prevent the release and spread of EEV, providing a distinct mechanism of protection compared to other viral targets (PubMed: 17507481). It is a key component in next-generation subunit vaccines and is a target of the antibodies found in Vaccinia Immune Globulin Intravenous (VIGIV) used to treat complications from smallpox vaccination (FDA: VIGIV Label). The protein's conserved nature across the Orthopoxvirus genus makes it a versatile target for broad-spectrum poxvirus countermeasures.
Induction of neutralizing antibodies that inhibit the formation and spread of extracellular enveloped virus (EEV) and block actin-mediated cell-to-cell transmission.
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