Immune profiling of mpox survivors reveals divergent durability of antibody and T cell responses

Despite the global spread of mpox virus (MPXV), the durability and breadth of infection-induced immunity remain incompletely defined. Here, we comprehensively characterize MPXV-specific antibody and T cell responses up to 18 months after natural infection in male individuals. Neutralizing antibodies exhibit typical acute viral kinetics, with titers peaking early and declining over time, from a mean of 328 at 12 months to 180 at 18 months post-infection. Neutralization analyses against MPXV clade Ib, clade IIb and VACV WR strains demonstrate pronounced cross-neutralization among orthopoxviruses, but with lineage-specific reductions in neutralization, indicating incomplete cross-reactivity across different lineages. In parallel, MPXV-specific CD4⁺ and Tfh cell responses remain robust and polyfunctional throughout follow-up, and CD8⁺ T cells maintain sustained responses characterized by cytokine production, together supporting durable cellular immunity. These findings offer critical insights into the durability and breadth of post-infection immunity, with implications for reinfection risk and orthopoxvirus vaccine strategies.

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Publication Details

Journal
Nature Communications
Published
2025-12-04
DOI
https://doi.org/10.1038/s41467-025-67266-7
Primary Topic
Poxvirus research and outbreaks
Type
article
Field-Weighted Citation Impact
0.00

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article

Immune profiling of mpox survivors reveals divergent durability of antibody and T cell responses

Jingjing Gao, Yongxia Shi, Canjie Chen, Jincun Zhao et al.
Nature Communications
Poxvirus research and outbreaks
article

Immune profiling of mpox survivors reveals divergent durability of antibody and T cell responses

Jingjing Gao, Yongxia Shi, Canjie Chen, Jincun Zhao, Pengzhe Qin, Qingtao Hu, Qun Zhong, Shuxiang Huang, Suxiang Li, Peilan Wei, Yanqun Wang, Xindan Xing, Jingxian Zhao, Airu Zhu, Yuanyuan Zhang, Lei Chen, Xinxin Li, Yang Yang, Zhiwei Lin, Zhaoyong Zhang, Jiantao Chen, Lijuan Zhou, Bin Qu, Xinyi Xiong, Hua Bai, Lu Zhang, Ruoxi Cai
article en

Abstract

Despite the global spread of mpox virus (MPXV), the durability and breadth of infection-induced immunity remain incompletely defined. Here, we comprehensively characterize MPXV-specific antibody and T cell responses up to 18 months after natural infection in male individuals. Neutralizing antibodies exhibit typical acute viral kinetics, with titers peaking early and declining over time, from a mean of 328 at 12 months to 180 at 18 months post-infection. Neutralization analyses against MPXV clade Ib, clade IIb and VACV WR strains demonstrate pronounced cross-neutralization among orthopoxviruses, but with lineage-specific reductions in neutralization, indicating incomplete cross-reactivity across different lineages. In parallel, MPXV-specific CD4⁺ and Tfh cell responses remain robust and polyfunctional throughout follow-up, and CD8⁺ T cells maintain sustained responses characterized by cytokine production, together supporting durable cellular immunity. These findings offer critical insights into the durability and breadth of post-infection immunity, with implications for reinfection risk and orthopoxvirus vaccine strategies.

Nature CommunicationsVol. 17(1)
Southern University of Science and Technology (CN), ShanghaiTech University (CN), Guangzhou Center for Disease Control and Prevention (CN), First Affiliated Hospital of Guangzhou Medical University (CN), Guangzhou Chemistry (China) (CN), Guangdong Provincial Center for Disease Control and Prevention (CN), State Key Laboratory of Respiratory Disease (CN), Guangdong Inspection and Quarantine Technology Center (China) (CN), Shenzhen Third People’s Hospital (CN), Guangzhou Medical University (CN)
State Key Laboratory of Respiratory Disease, National Natural Science Foundation of China, General Administration of Customs, National Key Research and Development Program of China
Openalex Percentile: Top 59%
Poxvirus research and outbreaks
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