A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein

Yongpeng Sun, Liqin Liu, Hongsheng Qiang, Hui Sun, Yichao Jiang, Luo Ren, Zemin Jiang, Siyu Lei, Li Chen, Yizhen Wang, Xue Lin, Guosong Wang, Yang Huang, Yuhao Fu, Yujin Shi, Xiuting Chen, Hai Yu, Shaowei Li, Wenxin Luo, Enmei Liu (), Qingbing Zheng (), Zizheng Zheng () and Ningshao Xia ()
Additional contact information
Yongpeng Sun: Xiamen University
Liqin Liu: Xiamen University
Hongsheng Qiang: Xiamen University
Hui Sun: Xiamen University
Yichao Jiang: Xiamen University
Luo Ren: Children’s Hospital of Chongqing Medical University
Zemin Jiang: Xiamen University
Siyu Lei: Xiamen University
Li Chen: Xiamen University
Yizhen Wang: Xiamen University
Xue Lin: Xiamen University
Guosong Wang: Xiamen University
Yang Huang: Xiamen University
Yuhao Fu: Xiamen University
Yujin Shi: Xiamen University
Xiuting Chen: Xiamen University
Hai Yu: Xiamen University
Shaowei Li: Xiamen University
Wenxin Luo: Xiamen University
Enmei Liu: Children’s Hospital of Chongqing Medical University
Qingbing Zheng: Xiamen University
Zizheng Zheng: Xiamen University
Ningshao Xia: Xiamen University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Respiratory syncytial virus (RSV) poses a significant public health challenge, especially among children. Although palivizumab and nirsevimab, neutralizing antibodies (nAbs) targeting the RSV F protein, have been used for prophylaxis, their limitations underscore the need for more effective alternatives. Herein, we present a potent and broad nAb, named 5B11, which exhibits nanogram level of unbiased neutralizing activities against both RSV-A and -B subgroups. Notably, 5B11 shows a ~20-fold increase in neutralizing efficacy compared to 1129 (the murine precursor of palivizumab) and approximately a 3-fold increase in neutralizing efficacy against B18537 in comparison to nirsevimab. Cryo-electron microscopy analysis reveals 5B11’s mechanism of action by targeting a highly conserved epitope within site V, offering a promising strategy with potentially lower risk of escape mutants. Antiviral testing in a female cotton rat model demonstrated that low-dose (1.5 mg/kg) administration of 5B11 achieved comparable prophylactic efficacy to that achieved by high-dose (15 mg/kg) of 1129. Furthermore, the humanized 5B11 showed a superior in vivo antiviral activity against B18537 infection compared to nirsevimab and palivizumab. Therefore, 5B11 is a promising RSV prophylactic candidate applicable to broad prevention of RSV infection.

Date: 2024
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DOI: 10.1038/s41467-024-54384-x

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