Antibody Binding and Neutralizing Targets within the Predicted Structure of the Poxvirus Multiprotein Entry-Fusion Complex.

ABSTRACT: The increased incidence of mpox emphasizes a need for new and improved vaccines. Poxviruses rely on a highly conserved but poorly characterized 11-protein entry-fusion complex (EFC), providing numerous potential targets. Here, we demonstrate that antibodies induced by six of 10 EFC proteins are neutralizing. Protein targets of the neutralizing and non-neutralizing antibodies are located within discrete regions of a model of the EFC predicted by AlphaFold3. Two newly identified targets, A16 and G9, at the apex of the EFC induced cross-neutralizing orthopoxvirus antibodies and protected female mice against a lethal VACV infection. Unexpectedly, antibodies to A16 and G9 were not detected following infection by attenuated or pathogenic VACV, likely due to physical sequestration of the proteins

SUBMITTER: Yu H 

PROVIDER: S-EPMC12190349 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature