The impact of orthopoxvirus vaccination and Mpox infection on cross-protective immunity: a multicohort observational study

作者：Jameson Crandell, Valter Silva Monteiro, Lauren Pischel, Zhenhao Fang, Luciana Conde, Yi Zhong, Lauren Lawres, Gustavo Meira de Asis, Gabriela Maciel, A. Zaleski, Guilherme S. Lira, Luiza M. Higa, Mallery I. Breban, Chantal B. F. Vogels, João Caria, Ana Raquel Pinto, Vasco Almeida, Fernando Maltêz, Rita Cordeiro, Diana Póvoas, Nathan D. Grubaugh, Lydia Barakat, Alba Grifoni, Alessandro Sette, Terezinha Marta Pereira Pinto Castiñeiras, Sidi Chen, İnci Yıldırım, André M. Vale, Saad B. Omer, Carolina Lucas · 发表于：The Lancet Microbe · 年份：2025 · DOI：10.1016/j.lanmic.2025.101098 · 被引用次数：27 · 研究领域：Poxvirus research and outbreaks、SARS-CoV-2 and COVID-19 Research、vaccines and immunoinformatics approaches

BACKGROUND: Cross-reactive immune memory responses to orthopoxviruses in humans remain poorly characterised despite their relevance for vaccine design and outbreak control. We aimed to assess the magnitude, specificity, and durability of cross-reactive immune responses elicited by smallpox vaccines and mpox virus infection. METHODS: We did a multicohort observational study involving participants from the USA, Brazil, and Portugal across four groups: Dryvax (first-generation smallpox vaccine) recipients vaccinated 40-80 years ago, JYNNEOS (third-generation smallpox vaccine) recipients vaccinated within the past year, a cohort receiving both vaccines, and patients infected with clade IIb mpox. Samples were analysed for systemic and mucosal humoral responses, neutralising antibody titres, viral antigen structural analysis, and T-cell cross-reactivity to vaccina virus, cowpox virus, and mpox virus. Statistical analyses included correlation assessments and comparisons across cohorts to determine the magnitude, longevity, and breadth of immune responses. FINDINGS: Between July 7, 2022, and Aug 3, 2023, 262 participants were recruited, resulting in analysis of 378 samples. Both first-generation and third-generation smallpox vaccines elicited vaccinia virus-reactive and mpox virus-reactive antibodies, with the strongest responses targeting the less conserved extracellular virion antigens B5 and A33. Despite high concentrations of anti-mpox virus antibodies in the plasma, cross-neutra...