The Screening of Broadly Neutralizing Antibodies Targeting the SARS-CoV-2 Spike Protein by mRNA Immunization in Mice
Zhiyin An,
Yu Zhang,
Xiang Yu,
Jia Xia,
Yanan Yin,
Guoming Li,
Jing Lu,
Xuemei Fan,
Yingjie Xu
Affiliations
Zhiyin An
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Yu Zhang
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Xiang Yu
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Jia Xia
Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Yanan Yin
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Guoming Li
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Jing Lu
Shanghai RNACure Biopharma Co., Ltd., Shanghai 200438, China
Xuemei Fan
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Yingjie Xu
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Neutralizing antibodies (nAbs), the popular antiviral drugs used for the treatment of COVID-19, are effective in reducing viral load and hospitalization. Currently, most nAbs are screened from convalescent or vaccinated individuals through single B-cell sequencing which requires cutting-edge facilities. Moreover, owing to the rapid mutation of SARS-CoV-2, some approved nAbs are no longer effective. In the present study, we designed a new approach to acquiring broadly neutralizing antibodies (bnAbs) from mRNA-vaccinated mice. Using the flexibility and speed of mRNA vaccine preparation, we designed a chimeric mRNA vaccine and sequential immunization strategies to acquire bnAbs in mice within a short period. By comparing different vaccination orders, we found that the initially administered vaccine had a greater effect on the neutralizing potency of mouse sera. Ultimately, we screened a strain of bnAb that neutralized wild-type, Beta, and Delta SARS-CoV-2 pseudoviruses. We synthesized the mRNAs of the heavy and light chains of this antibody and verified its neutralizing potency. This study developed a new strategy to screen for bnAbs in mRNA-vaccinated mice and identified a more effective immunization strategy for inducing bnAbs, providing valuable insights for future antibody drug development.
