Cross-reactive antibody response to Monkeypox virus surface proteins in a small proportion of individuals with and without Chinese smallpox vaccination history

Anqi Xia; Xiaojie Wang; Jiaying He; Wei Wu; Weiyu Jiang; Song Xue; Qianqian Zhang; Yidan Gao; Yuru Han; Yaming Li; Xiaofang Peng; Minxiang Xie; Christian T Mayer; Jie Liu; Chen Hua; Yiou Sha; Wei Xu; Jinghe Huang; Tianlei Ying; Shibo Jiang; Youhua Xie; Qiliang Cai; Lu Lu; Israel T Silva; Zhenghong Yuan; Yixiao Zhang; Qiao Wang

doi:10.1186/s12915-023-01699-8

Cross-reactive antibody response to Monkeypox virus surface proteins in a small proportion of individuals with and without Chinese smallpox vaccination history

BMC Biol. 2023 Oct 2;21(1):205. doi: 10.1186/s12915-023-01699-8.

Authors

Anqi Xia^#¹, Xiaojie Wang^#², Jiaying He^#¹, Wei Wu¹, Weiyu Jiang¹, Song Xue¹, Qianqian Zhang¹, Yidan Gao¹, Yuru Han¹, Yaming Li¹, Xiaofang Peng¹, Minxiang Xie¹, Christian T Mayer³, Jie Liu⁴, Chen Hua¹, Yiou Sha¹, Wei Xu¹, Jinghe Huang¹, Tianlei Ying¹, Shibo Jiang¹, Youhua Xie¹, Qiliang Cai¹, Lu Lu⁵, Israel T Silva⁶, Zhenghong Yuan⁷, Yixiao Zhang⁸, Qiao Wang⁹

Affiliations

¹ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
² The Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China.
³ Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
⁴ Department of Respiratory and Critical Care Medicine, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, Jiangsu, China.
⁵ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. lul@fudan.edu.cn.
⁶ Laboratory of Bioinformatics and Computational Biology, A. C. Camargo Cancer Center, São Paulo, SP, 01509-010, Brazil. itojal@accamargo.org.br.
⁷ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. zhyuan@shmu.edu.cn.
⁸ The Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China. yzhang@mail.sioc.ac.cn.
⁹ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. wangqiao@fudan.edu.cn.

^# Contributed equally.

Abstract

Background: After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all.

Results: We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV).

Conclusions: We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.

Keywords: Antibody; Monkeypox virus; Serological ELISA; Smallpox vaccination; VACV Tiantan Strain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibody Formation
China
Cross Reactions*
East Asian People
Humans
Membrane Proteins
Mice
Monkeypox virus*
Smallpox / prevention & control
Smallpox Vaccine* / immunology
Smallpox Vaccine* / therapeutic use
Vaccination*
Vaccinia virus
Young Adult

Substances

Membrane Proteins
Smallpox Vaccine