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.