2. Academic Validation
  3. A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein

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

  • Nat Commun. 2024 Nov 21;15(1):10085. doi: 10.1038/s41467-024-54384-x.
Yongpeng Sun # 1 2,  Liqin Liu # 1 2,  Hongsheng Qiang # 1 2,  Hui Sun # 1 2,  Yichao Jiang # 1 2,  Luo Ren # 3,  Zemin Jiang # 1 2,  Siyu Lei 1 2,  Li Chen 1 2,  Yizhen Wang 1 2,  Xue Lin 1 2,  Guosong Wang 1 2,  Yang Huang 1 2,  Yuhao Fu 1 2,  Yujin Shi 1 2,  Xiuting Chen 1 2,  Hai Yu 1 2,  Shaowei Li 1 2,  Wenxin Luo 1 2,  Enmei Liu 4,  Qingbing Zheng 5 6,  Zizheng Zheng 7 8,  Ningshao Xia 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China.
  • 2 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, P. R. China.
  • 3 Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, P. R. China.
  • 4 Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, P. R. China. emliu186@126.com.
  • 5 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China. abing0811@xmu.edu.cn.
  • 6 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, P. R. China. abing0811@xmu.edu.cn.
  • 7 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China. zhengzizheng@xmu.edu.cn.
  • 8 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, P. R. China. zhengzizheng@xmu.edu.cn.
  • 9 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China. nsxia@xmu.edu.cn.
  • 10 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, P. R. China. nsxia@xmu.edu.cn.
  • # Contributed equally.
PMID: 39572535 DOI: 10.1038/s41467-024-54384-x
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.

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