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Peer reviewedOpen accessSmallpoxMonkeypox

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

International Journal of Infectious Diseases·

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

DOI
10.1016/j.ijid.2026.109047
PMID
42604648
PMCID
OpenAlex
W7203588703
Study type
Journal article
Publisher
Elsevier BV
Article type
journal-article
Integrity
current

Why this research matters now

Monkeypox infection and smallpox vaccination may provide cross-protection against orthopoxviruses. Early IgA detection could support mpox diagnosis in asymptomatic high-risk individuals, and complement-dependent neutralization assays may improve cross-immunity assessment.

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Structured evidence summary

Research question

The study assessed humoral cross-reactivity against orthopoxviruses in individuals infected with clade IIb monkeypox virus and in healthcare workers who received the MVA-BN smallpox vaccine.

Study design

Participants were followed longitudinally from monkeypox symptom onset or MVA-BN vaccination. Binding antibodies were measured by indirect immunofluorescence, and neutralizing antibodies were assessed using plaque reduction neutralization assays and a complement-dependent neutralization assay with MVA-eGFP.

Population and setting

The study included individuals infected with clade IIb monkeypox virus and healthcare workers receiving third-generation MVA-BN smallpox vaccine.

Main findings

Monkeypox infection elicited orthopoxvirus-reactive IgA and IgM within a median of 11 days after symptom onset, with IgG rising over time. Neutralizing antibodies against monkeypox and vaccinia viruses remained sustained to a median of 65 days after symptom onset, whereas cowpox neutralizing antibodies declined significantly. MVA-BN vaccinees maintained vaccinia-reactive IgG for two years post-vaccination, though titers decreased over time, and demonstrated cross-reactive neutralizing capacity throughout. Exogenous complement increased the sensitivity of the MVA-eGFP neutralization assay, and both infection and vaccination induced MVA-eGFP neutralizing antibodies that correlated significantly with orthopoxvirus neutralizing antibodies.

Public-health relevance

Monkeypox infection and smallpox vaccination may provide cross-protection against orthopoxviruses. Early IgA detection could support mpox diagnosis in asymptomatic high-risk individuals, and complement-dependent neutralization assays may improve cross-immunity assessment.

Important limitations

This summary relies on the supplied single-article abstract and metadata. The original paper is required for decision-grade interpretation, including detailed methods, sample characteristics, and statistical analyses.

GIDS interpretation

The study is discoverable through classifier links for smallpox, monkeypox, Cabo Verde, vaccination, and vaccine effectiveness. These links reflect study scope and do not indicate an active surveillance signal or outbreak context.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 9 auditable classifier relationships to diseases, places, topics, and study design.

about diseaseabout diseaseaddresses topicaddresses topicevaluates interventionhas pathogen typestudied population settingstudies pathogenuses study design