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. ### Competing Interest Statement M.J.M. reported potential competing interests: laboratory research and clinical trials contracts for vaccines or MAB with Lilly, Pfizer, and Sanofi; research grant funding from USG/HHS/NIH for vaccine and MAB clinical trials; personal fees for Scientific Advisory Board service from Hillevax, Merck, Meissa Vaccines, Inc. and Pfizer. ### Funding Statement Financial support was provided by the Blavatnik Family Foundation, the National Institutes of Health (NIH) grants no. AI148574 and 75N93021C00014 (to M.J.M.), the NYC Department of Health and Mental Hygiene, and NYU Grossman School of Medicine institutional support. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of NYU Grossman School of Medicine gave ethical approval for this work (protocol 22-01338). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.