Cross-reactive immunity against orthopoxviruses after monkeypox virus infection or smallpox vaccination.

Authors

Maria Trovato, Silvia Accordini, Natasha Gianesini, Lorena Maria Chesini, Samuele Cheri, Gabriella Cotugno, Andrea Matucci, Annalisa Donini, Rebeca Passarelli Mantovani, Irene Cassaniti, Francesca Rovida, Alessandro Ferrari, Cristina Mazzi, Evelina Tacconelli, Fausto Baldanti, Maria Rosaria Capobianchi, Antonino Di Caro, Piergiuseppe De Berardinis, Luciana D'Apice, Concetta Castilletti

Published in

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. Pages 109047. Aug 16, 2026. Epub Aug 16, 2026.

Abstract

Global spread of monkeypox virus (MPV) underscored the importance to monitor vaccine effectiveness and cross-protective immunity against MPV and orthopoxviruses (OPXVs), as vaccinia virus (VACV) and cowpox virus (CPV). This study evaluated humoral OPXV cross-reactivity in clade IIb MPV-infected individuals or healthcare workers receiving MVA-BN third-generation smallpox vaccine.
Participants were followed from mpox symptom onset (SO) or MVA-BN vaccination. Binding and neutralizing antibodies were measured by Indirect Immunofluorescence and Plaque Reduction Neutralization assays. Complement-dependent neutralization assay using MVA-eGFP was performed exploiting a high-content imaging system.
MPV infection induced OPXV-reactive IgA and IgM within 11 days (median) after SO, with IgG increasing over time. MPV and VACV neutralizing antibodies (nAbs) were sustained and persisted to 65 days (median) from SO, while CPV nAbs significantly waned. MVA-BN vaccinees displayed persistent VACV-reactive IgG through two years after vaccination, with titers declining throughout, and cross-reactive neutralizing capacity over two years. Exogenous complement enhanced sensitivity of MVA-eGFP neutralization assay. Infection and vaccination induced MVA-eGFP nAbs significantly correlating with OPXV nAbs.
MPV infection and smallpox vaccination might confer OPXV cross-protection. IgA may support early mpox diagnosis, particularly in asymptomatic high-risk individuals. Complement-dependent neutralization assay may improve assessment of cross-immunity.

PMID:
42604648
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

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