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Short-Lived Neutralizing Antibody Responses to Monkeypox Virus in Smallpox Vaccine–Naive Persons after JYNNEOS Vaccination

Kara Phipps, Jennifer L. Yates, Jessica Pettit, Sean Bialosuknia, Danielle Hunt, Alan P. Dupuis, Anne F. Payne, William T. Lee, Kathleen A. McDonough

2025Emerging infectious diseases13 citationsDOIOpen Access PDF

Abstract

JYNNEOS, a third-generation smallpox vaccine, is integral to monkeypox virus (MPXV) control efforts, but the durability of this modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine's effectiveness is undefined. We optimized and used a plaque reduction neutralization test (PRNT) with authentic clade IIa MPXV and vaccinia virus to assess antibody responses over 12 months in 8 donors vaccinated with 2 doses of JYNNEOS. One donor previously received the ACAM2000 vaccine; 7 donors were smallpox vaccine-naive. IgG responses of the donors to vaccinia virus (L1, B5, and A33) or MPXV (E8, H3, A35) antigens and PRNT titers to both viruses peaked at 8 weeks postvaccination and waned rapidly thereafter in naive donors. MPXV PRNT titers were especially low; no naive donors demonstrated 90% plaque reduction. These data indicate a need for improved correlates of MPXV immunity to enable MVA-BN durability studies, given that recent clinical data support MVA-BN vaccine efficacy against MPXV despite low antibody responses.

Topics & Concepts

MonkeypoxVirologySmallpox vaccineSmallpoxVaccinationAntibodyVacciniaMedicineImmunologyBiologyBiochemistryRecombinant DNAGenePoxvirus research and outbreaksBacillus and Francisella bacterial researchHerpesvirus Infections and Treatments
Short-Lived Neutralizing Antibody Responses to Monkeypox Virus in Smallpox Vaccine–Naive Persons after JYNNEOS Vaccination | Litcius