Broad neutralizing antibody response of a monomeric spike–based SARS-CoV-2 bivalent vaccine against diverse variants
Abstract
severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) bivalent vaccines show potential against variants but lack a full understanding of the immunological mechanisms that drive broadly neutralizing antibodies (bnAbs). This study explored the immunogenicity of a bivalent vaccine in rhesus macaques, containing spike (S) proteins from the prototype (S prototype ) and chimeric S protein (S 1628x ). The vaccine induced bnAbs against multiple variants, including challenging subvariants like EG.1, BA.2.86, and JN.1. The monomeric S protein exposed less accessible regions within the receptor-binding domain (RBD) “inner face” and “NTD face” and subdomains 1, eliciting a diverse array of bnAbs against various Omicron subvariants. Notably, antibodies targeting the conserved RBD inner face, such as 4A5, showed potent neutralization across all tested variants. Structural analyses provide insights into the broad protectiveness of these vaccine-elicited nAbs. This study underscores the potential of bivalent vaccines with monomeric spike proteins to confer broad-spectrum immunity, offering a promising direction for future SARS-CoV-2 universal vaccine design.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (30)
Siling Wang
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Hui Sun
Yizhen Wang
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Zikang Wang
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Lunzhi Yuan
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Huilin Guo
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Jiahua Gao
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Miaolin Lan
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Yangtao Wu
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Huixian Shang
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Xiuting Chen
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Zheng Chen
Jiayi Hu
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Zimin Tang
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Guiping Wen
Department of Central Laboratory, Women and Children’s Hospital, School of Medicine, Xiamen University
Dong Ying
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Chang Liu
Yanan Jiang
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Jinfu Su
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Min Lin
Ting Wu
Children’s Hospital, Zhejiang University School of Medicine
Shaowei Li
Department of Chemistry
Tianying Zhang
Jun Zhang
Yi Guan
State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Ningshao Xia
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Quan Yuan
Qingbing Zheng
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University
Yali Zhang
Zizheng Zheng
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University