Broad neutralizing antibody response of a monomeric spike–based SARS-CoV-2 bivalent vaccine against diverse variants
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<sub>prototype</sub>) and chimeric S protein (S<sub>1628x</sub>). 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.
Authors
- Tianying Zhang (ORCID: https://orcid.org/0000-0002-2477-329X)
- Yangtao Wu (ORCID: https://orcid.org/0000-0002-9429-266X)
- Ting Wu (ORCID: https://orcid.org/0000-0002-1806-3056)
- Huixian Shang
- Qingbing Zheng (ORCID: https://orcid.org/0000-0002-7516-9965)
- Xiuting Chen
- Zikang Wang (ORCID: https://orcid.org/0000-0003-1406-1237)
- Yi Guan (ORCID: https://orcid.org/0000-0001-6057-9243)
- Ying Dong (ORCID: https://orcid.org/0000-0002-2976-3111)
- Lunzhi Yuan (ORCID: https://orcid.org/0000-0001-7480-0287)
- Guiping Wen (ORCID: https://orcid.org/0009-0001-2403-5924)
- Zimin Tang (ORCID: https://orcid.org/0000-0002-9326-2514)
- Zizheng Zheng (ORCID: https://orcid.org/0000-0003-0099-4212)
- Ningshao Xia (ORCID: https://orcid.org/0000-0003-0179-5266)
- Miaolin Lan
- Quan Yuan (ORCID: https://orcid.org/0000-0001-5487-561X)
- Jiahua Gao
- Chang Liu (ORCID: https://orcid.org/0000-0001-6619-7019)
- Zheng Chen (ORCID: https://orcid.org/0000-0002-1978-1447)
- Yizhen Wang (ORCID: https://orcid.org/0000-0003-1470-8344)
- Jun Zhang (ORCID: https://orcid.org/0000-0002-5843-8705)
- Shaowei Li (ORCID: https://orcid.org/0000-0002-3374-1038)
- Hui Sun (ORCID: https://orcid.org/0009-0006-9866-9846)
- Huilin Guo
- Siling Wang (ORCID: https://orcid.org/0000-0001-5485-0818)
- Yanan Jiang (ORCID: https://orcid.org/0000-0002-8964-7155)
- Yali Zhang (ORCID: https://orcid.org/0000-0002-8328-0591)
- Min Lin (ORCID: https://orcid.org/0000-0001-8496-0479)
- Jiayi Hu
- Jinsheng Su
Institutions
- Xiamen University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Frontier Medical College (PK)
- Shantou University (CN)
- Center for Innovation (US)
- Children’s Hospital of Fudan University Xiamen Branch (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-08-25
- DOI
- https://doi.org/10.1073/pnas.2503254122
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00