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The Monkeypox virus (MPXV) antigens A35, B6, M1, and H3 represent a strategic combination of viral surface proteins utilized in next-generation vaccine development, most notably in Moderna's mRNA-1769 candidate. These antigens are homologs of the Vaccinia virus proteins A33R, B5R, L1R, and H3L, respectively, and play distinct yet complementary roles in the viral life cycle (Nature Communications: 10.1038/s41467-023-41939-4). M1 and H3 are essential components of the intracellular mature virus (IMV) membrane, mediating host cell attachment via heparan sulfate and facilitating viral entry. Conversely, A35 and B6 are specific to the extracellular enveloped virus (EEV) form, where they are required for efficient viral egress and actin-mediated cell-to-cell spread (PubMed: 37735475). By incorporating all four antigens, therapeutic interventions aim to elicit a synergistic immune response that neutralizes both infectious forms of the virus, thereby preventing both initial infection and systemic dissemination. This multi-antigen approach is designed to provide broader and more durable protection compared to single-antigen strategies, particularly against emerging orthopoxvirus variants. Clinical monitoring of these targets typically involves measuring the induction of neutralizing antibodies and antigen-specific T-cell activation (Moderna: mRNA-1769).
Induction of neutralizing antibodies and cellular immunity against the intracellular mature virus (IMV) and extracellular enveloped virus (EEV) forms of the monkeypox virus.
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