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Published on: September 15, 2010
A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein
Yongpeng Sun1,2, Liqin Liu1,2, Hongsheng Qiang1,2
1State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, P. R. China.
Insights
A new neutralizing antibody, 5B11, offers potent protection against Respiratory Syncytial Virus (RSV) subgroups A and B. This promising RSV prophylactic candidate demonstrates superior efficacy and a lower risk of mutant escape compared to existing treatments.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Respiratory Syncytial Virus (RSV) is a major global health concern, particularly for pediatric populations.
- Current prophylactic options like palivizumab and nirsevimab have limitations, necessitating the development of improved therapies.
Purpose of the Study:
- To introduce and characterize a novel, potent, and broad-acting neutralizing antibody, designated 5B11, for RSV prophylaxis.
- To evaluate the neutralizing activity and in vivo efficacy of 5B11 against RSV-A and RSV-B.
Main Methods:
- In vitro neutralization assays were performed to assess 5B11's activity against RSV subgroups.
- Cryo-electron microscopy was utilized to elucidate the binding epitope and mechanism of action.
- Antiviral efficacy was tested in a cotton rat model using low-dose 5B11 and compared to existing antibodies.
Main Results:
- 5B11 demonstrated potent, unbiased neutralizing activity against both RSV-A and RSV-B at nanogram levels.
- It exhibited significantly higher neutralizing efficacy than palivizumab's precursor (1129) and nirsevimab.
- Cryo-EM revealed targeting of a conserved epitope in site V, suggesting reduced escape mutant risk.
- In vivo studies showed 5B11 achieved comparable efficacy to high-dose 1129 at a significantly lower dose and outperformed nirsevimab and palivizumab.
Conclusions:
- 5B11 is a highly effective neutralizing antibody with broad activity against RSV.
- Its unique binding site and superior in vivo performance position it as a promising candidate for broad RSV infection prevention.
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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