The Durability and Avidity of MPXV-specific Antibodies Induced by the Two-dose MVA-BN Mpox Vaccine

The 2022 global outbreak of clade IIb mpox was the first major outbreak of mpox outside of African nations. To control the outbreak, vaccination campaigns were begun using the third-generation orthopoxvirus vaccine MVA-BN. During the vaccination campaign, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI). NYC OSMI is a longitudinal study that enrolled 171 MVA-BN vaccinees with or without prior smallpox vaccination and mpox convalescent individuals. Study participants had blood drawn prior to vaccination, after one dose, and after two doses. Mpox virus (MPXV) neutralizing titers in sera reach a comparable peak in naïve and experienced vaccinees. However, neutralizing titers return to baseline in less than one year for naïve individuals, while remaining elevated in those with prior smallpox vaccination. Both naïve and experienced individuals generate robust, immunodominant IgG responses against MPXV H3 and A35, but with significantly lower avidity in naïve vaccinees. Their vaccinia virus homologs H3 and A33 have previously been shown to be protective targets for orthopoxvirus infection and disease in mouse models. These data highlight a low avidity antibody response elicited by MVA-BN that is short-lived in naïve vaccinees. This study supports the need for studies of long-term protection from MVA-BN, the potential need for booster doses, and further development of next-generation orthopoxvirus vaccines.