Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus
Abstract The global outbreak of monkeypox virus (MPXV), combined with the termination of smallpox vaccination and the lack of specific antiviral treatments, raises increasing concerns. The surface proteins M1R and B6R of MPXV are crucial for virus transmission and serve as key targets for vaccine de...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58180-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850258805321891840 |
|---|---|
| author | Yuanyuan Qu Wanbo Tai Enhao Ma Qiwei Jiang Miao Fan Wangcheng Xiao Chongyu Tian Yang Liu Jianying Liu Xinquan Wang Jiwan Ge Gong Cheng |
| author_facet | Yuanyuan Qu Wanbo Tai Enhao Ma Qiwei Jiang Miao Fan Wangcheng Xiao Chongyu Tian Yang Liu Jianying Liu Xinquan Wang Jiwan Ge Gong Cheng |
| author_sort | Yuanyuan Qu |
| collection | DOAJ |
| description | Abstract The global outbreak of monkeypox virus (MPXV), combined with the termination of smallpox vaccination and the lack of specific antiviral treatments, raises increasing concerns. The surface proteins M1R and B6R of MPXV are crucial for virus transmission and serve as key targets for vaccine development. In this study, a panel of human antibodies targeting M1R and B6R is isolated from a human antibody library using phage display technology. Among these antibodies, A138 against M1R and B026 against B6R show the most potent broad-spectrum neutralizing activities against MPXV and Vaccinia virus (VACV). When used in combination, A138 and B026 exhibit complementary neutralizing activity against both viruses in vitro. X-ray crystallography reveales that A138 binds to the loop regions of M1R, similar to the vulnerable epitope of 7D11 on VACV L1R. By contrast, A129 targets a more cryptic epitope, primarily comprising the β-strands of M1R. Moreover, prophylactic and therapeutic administration of A138 or B026 alone provides partial protection, while combining these two antibodies results in enhanced protection against VACV in male C57BL/6 mice. This study demonstrates of a dual-targeting strategy using two different components of the virion for the prevention and treatment of MPXV infection. |
| format | Article |
| id | doaj-art-2766eae8fdda47fabf7e8f64cf49bb3b |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2766eae8fdda47fabf7e8f64cf49bb3b2025-08-20T01:56:01ZengNature PortfolioNature Communications2041-17232025-04-0116111610.1038/s41467-025-58180-zGeneration and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virusYuanyuan Qu0Wanbo Tai1Enhao Ma2Qiwei Jiang3Miao Fan4Wangcheng Xiao5Chongyu Tian6Yang Liu7Jianying Liu8Xinquan Wang9Jiwan Ge10Gong Cheng11Institute of Infectious Diseases, Shenzhen Bay LaboratoryInstitute of Infectious Diseases, Shenzhen Bay LaboratoryNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua UniversityChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and ControlKey Laboratory of Pathogen Infection Prevention and Control (MOE), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Infectious Diseases, Shenzhen Bay LaboratoryInstitute of Infectious Diseases, Shenzhen Bay LaboratoryInstitute of Infectious Diseases, Shenzhen Bay LaboratoryInstitute of Infectious Diseases, Shenzhen Bay LaboratoryThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua UniversityKey Laboratory of Pathogen Infection Prevention and Control (MOE), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua UniversityAbstract The global outbreak of monkeypox virus (MPXV), combined with the termination of smallpox vaccination and the lack of specific antiviral treatments, raises increasing concerns. The surface proteins M1R and B6R of MPXV are crucial for virus transmission and serve as key targets for vaccine development. In this study, a panel of human antibodies targeting M1R and B6R is isolated from a human antibody library using phage display technology. Among these antibodies, A138 against M1R and B026 against B6R show the most potent broad-spectrum neutralizing activities against MPXV and Vaccinia virus (VACV). When used in combination, A138 and B026 exhibit complementary neutralizing activity against both viruses in vitro. X-ray crystallography reveales that A138 binds to the loop regions of M1R, similar to the vulnerable epitope of 7D11 on VACV L1R. By contrast, A129 targets a more cryptic epitope, primarily comprising the β-strands of M1R. Moreover, prophylactic and therapeutic administration of A138 or B026 alone provides partial protection, while combining these two antibodies results in enhanced protection against VACV in male C57BL/6 mice. This study demonstrates of a dual-targeting strategy using two different components of the virion for the prevention and treatment of MPXV infection.https://doi.org/10.1038/s41467-025-58180-z |
| spellingShingle | Yuanyuan Qu Wanbo Tai Enhao Ma Qiwei Jiang Miao Fan Wangcheng Xiao Chongyu Tian Yang Liu Jianying Liu Xinquan Wang Jiwan Ge Gong Cheng Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus Nature Communications |
| title | Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus |
| title_full | Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus |
| title_fullStr | Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus |
| title_full_unstemmed | Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus |
| title_short | Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus |
| title_sort | generation and characterization of neutralizing antibodies against m1r and b6r proteins of monkeypox virus |
| url | https://doi.org/10.1038/s41467-025-58180-z |
| work_keys_str_mv | AT yuanyuanqu generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT wanbotai generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT enhaoma generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT qiweijiang generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT miaofan generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT wangchengxiao generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT chongyutian generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT yangliu generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT jianyingliu generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT xinquanwang generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT jiwange generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus AT gongcheng generationandcharacterizationofneutralizingantibodiesagainstm1randb6rproteinsofmonkeypoxvirus |