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Novel BA.4/5 Bivalent SARS-CoV-2 mRNA Vaccine Provides Broad Protection Against SARS-CoV-2 Emerging Variants

Haomeng Wang, Jin Li, Zhao Chen, Dou Wu, Xiuwen Sui, Canjie Chen, Jun Dai, Chenlong Hu,Zhihong Yan, Jianming Shi, Yingying Liu, Jie Deng, Quan Liu, Liqiao Ma, Shuxiang Huang, Lan Chen,Jinling Cheng, Xiaoou Dong, Jian Liu, Dongxu Qiu, Jincun Zhao, Tao Zhu

The worldwide pandemic is still being driven by the emergence of SARS-CoV-2 variants that appear to evade antibody neutralization, therefore, there is a constant demand to broaden vaccine-induced immunity. In this study, we assessed the immunogenicity of two bivalent mRNA vaccines that contain CS-2034, our first-generation monovalent vaccine, and an mRNA vaccine encoding the spike protein of one of the recent Omicron variants, either BA.1 or BA.4/5. When administered as a primary immunization series in BALB/c mice, the BA.4/5 bivalent vaccine induced broader neutralizing antibody responses against a variety of SARS-CoV-2 variants, including the original strain, as well as the BA.1, BA.2.75, BA.4/5, and XBB.1 variants, compared to other vaccine candidates. As a heterologous booster after the primary vaccination series with two doses of inactivated vaccine (BBIBP-CorV, Sinopharm), the BA.4/5 bivalent vaccines elicited a greater amount of neutralizing antibodies than the BBIBP-CorV homologous booster and constituent monovalent vaccines, even at lower doses. Thus, the BA.4/5 bivalent mRNA vaccine has excellent promise for clinical use against the present variants of concern (VOCs) of SARS-CoV-2.

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