JYNNEOS Vaccination Induced Short-Lived Neutralizing Antibody Responses to Monkeypox Virus in Naive Individuals

Current studies of the JYNNEOS-induced neutralizing antibody response to monkeypox virus (MPXV) are limited by either short-term durability data, quantification in an endemic population, or lack of an infectious MPXV neutralization assay. We used plaque reduction neutralization test (PRNT) with authentic MPXV and vaccinia viruse (VACV) to assess antibody responses over twelve months of eight donors vaccinated with two doses of JYNNEOS. One donor previously received the ACAM2000 vaccine; seven donors were smallpox-vaccine naive. The IgG response of the donors to VACV (L1R, B5R, and A33R) and MPXV (E8L, H3L, A35R) antigens and PRNT titers to both viruses peaked at eight weeks post-vaccination and waned thereafter in naive donors. MPXV PRNT titers were especially low; no naive donors produced a detectable PRNT90 titer. Our results suggest the MPXV humoral response produced by JYNNEOS is limited in naive donors and invites further investigation into current mpox vaccination strategies and correlates of protection. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported in part by New York State Department of Health and funding from the US Centers for Disease Control (CDC) grant [NU50CK000516]. ### 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 New York State Institutional Review Board has deemed this study Non-human subject research. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 work are contained in the manuscript or supplemental materials.