A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein
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.
Authors
- Liqin Liu (ORCID: https://orcid.org/0000-0001-7158-6772)
- Qingbing Zheng (ORCID: https://orcid.org/0000-0002-7516-9965)
- Ren Luo (ORCID: https://orcid.org/0000-0001-9508-5497)
- Yuhao Fu (ORCID: https://orcid.org/0009-0005-9331-896X)
- Xiuting Chen
- Yang Huang (ORCID: https://orcid.org/0000-0002-6458-6069)
- Yongpeng Sun (ORCID: https://orcid.org/0000-0003-3836-5083)
- Hongsheng Qiang
- Yichao Jiang (ORCID: https://orcid.org/0009-0001-8657-2776)
- Ze-Min Jiang
- Hai Jing Yu (ORCID: https://orcid.org/0000-0003-4086-8632)
- Guosong Wang (ORCID: https://orcid.org/0000-0001-6202-2860)
- Zizheng Zheng (ORCID: https://orcid.org/0000-0003-0099-4212)
- Ningshao Xia (ORCID: https://orcid.org/0000-0003-0179-5266)
- Enmei Liu (ORCID: https://orcid.org/0000-0001-8503-6974)
- Li Chen (ORCID: https://orcid.org/0000-0002-8013-5508)
- Wenxin Luo (ORCID: https://orcid.org/0000-0002-0557-3196)
- Yizhen Wang (ORCID: https://orcid.org/0000-0003-1470-8344)
- Shaowei Li (ORCID: https://orcid.org/0000-0002-3374-1038)
- Hui Sun (ORCID: https://orcid.org/0009-0006-9866-9846)
- Siyu Lei
- Yujin Shi
- Xue Lin
Institutions
- Xiamen University (CN)
- Children's Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-21
- DOI
- https://doi.org/10.1038/s41467-024-54384-x
- Citations
- 18
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 6.96
Funders
- National Natural Science Foundation of China
- Xiamen University
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities