Target intelligence / Profile preview

Monkeypox virus antigens A35, B6, M1, and H3 (A35/B6/M1/H3)

Target
A35/B6/M1/H3
Molecular classification
Viral surface protein, Antigen
01

Overview

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).

Other names
MPXV A35RMPXV B6RMPXV M1RMPXV H3LA33R homologB5R homologL1R homologH3L homologOPG188OPG210OPG094OPG111
02

Mechanism of action

Induction of neutralizing antibodies and cellular immunity against the intracellular mature virus (IMV) and extracellular enveloped virus (EEV) forms of the monkeypox virus.

03

Biological functions

Viral attachmentViral entryViral egressCell-to-cell spreadImmune response
04

Disease associations

MpoxOrthopoxvirus infection
05

Safety considerations

Injection site reactionsSystemic vaccine-related side effects (fever, fatigue, myalgia)Potential for antibody-dependent enhancement (theoretical)
06

Interacting drugs

mRNA-1769

1 more in the full profile.

07

Biomarkers

Neutralizing antibody titersAntigen-specific IgG levelsT-cell response

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