A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein
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...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54384-x |
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| author | 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 Ningshao Xia |
| author_facet | 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 Ningshao Xia |
| author_sort | Yongpeng Sun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b23b88b2a7fb411f9b4d0edab0dc6109 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b23b88b2a7fb411f9b4d0edab0dc61092024-11-24T12:35:20ZengNature PortfolioNature Communications2041-17232024-11-0115111610.1038/s41467-024-54384-xA potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F proteinYongpeng Sun0Liqin Liu1Hongsheng Qiang2Hui Sun3Yichao Jiang4Luo Ren5Zemin Jiang6Siyu Lei7Li Chen8Yizhen Wang9Xue Lin10Guosong Wang11Yang Huang12Yuhao Fu13Yujin Shi14Xiuting Chen15Hai Yu16Shaowei Li17Wenxin Luo18Enmei Liu19Qingbing Zheng20Zizheng Zheng21Ningshao Xia22State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityDepartment of Respiratory Medicine, Children’s Hospital of Chongqing Medical UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityDepartment of Respiratory Medicine, Children’s Hospital of Chongqing Medical UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityAbstract 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.https://doi.org/10.1038/s41467-024-54384-x |
| spellingShingle | 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 Ningshao Xia A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein Nature Communications |
| title | A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein |
| title_full | A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein |
| title_fullStr | A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein |
| title_full_unstemmed | A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein |
| title_short | A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein |
| title_sort | potent broad spectrum neutralizing antibody targeting a conserved region of the prefusion rsv f protein |
| url | https://doi.org/10.1038/s41467-024-54384-x |
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