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
  • 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. [email protected].
  • 5. State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China. [email protected].
  • 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. [email protected].
  • 7. State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China. [email protected].
  • 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. [email protected].
  • 9. State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China. [email protected].
  • 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. [email protected].
  • # 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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