Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodies
Summary: Human cytomegalovirus (hCMV) poses a severe threat to fetuses, newborns, and immunocompromised individuals. No approved vaccines and limited treatment options are current medical challenges. Here, we analyze the human B cell responses to glycoprotein B (gB) in three top hCMV neutralizers fr...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004176 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850273495934566400 |
|---|---|
| author | Changwen Wu Nan Song Yizhen Zhao Han Wang Yuanbao Ai Yayu Wang Yueming Wang Xiaohui Yuan Tong Liu Nan Li Dabbu Kumar Jaijyan Chengming Li Lei Zhang Weihong Zheng Zhiwei Yang Shujia Zhu Hua-Xin Liao |
| author_facet | Changwen Wu Nan Song Yizhen Zhao Han Wang Yuanbao Ai Yayu Wang Yueming Wang Xiaohui Yuan Tong Liu Nan Li Dabbu Kumar Jaijyan Chengming Li Lei Zhang Weihong Zheng Zhiwei Yang Shujia Zhu Hua-Xin Liao |
| author_sort | Changwen Wu |
| collection | DOAJ |
| description | Summary: Human cytomegalovirus (hCMV) poses a severe threat to fetuses, newborns, and immunocompromised individuals. No approved vaccines and limited treatment options are current medical challenges. Here, we analyze the human B cell responses to glycoprotein B (gB) in three top hCMV neutralizers from a cohort of 283 individuals with latent-infected hCMV. By single-cell amplification of memory B cells, we identify a cluster of potent neutralizing monoclonal antibodies (nAbs) that competitively recognize an unknown vulnerable site on gB antigenic domain 5 (AD-5). This cluster of nAbs functionally outperforms the nAbs utilized in clinical trials. Cryoelectron microscopy (cryo-EM) unveils the structural basis of the neutralization mechanism of an antibody directly targeting the fusion subdomain on AD-5. Moreover, immunological analyses of human and mouse sera have preliminarily validated the potential superiority of AD-5-focused immune responses. Overall, our results will support the development of optimized gB-based vaccines and provide promising prophylactic and therapeutic antibody candidates against hCMV infection. |
| format | Article |
| id | doaj-art-5c2018df77a5462ab8f898ec8b9bcae2 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-5c2018df77a5462ab8f898ec8b9bcae22025-08-20T01:51:28ZengElsevierCell Reports2211-12472025-05-0144511564610.1016/j.celrep.2025.115646Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodiesChangwen Wu0Nan Song1Yizhen Zhao2Han Wang3Yuanbao Ai4Yayu Wang5Yueming Wang6Xiaohui Yuan7Tong Liu8Nan Li9Dabbu Kumar Jaijyan10Chengming Li11Lei Zhang12Weihong Zheng13Zhiwei Yang14Shujia Zhu15Hua-Xin Liao16Trinomab Pharmaceutical Co., Ltd., Zhuhai 519040, China; Corresponding authorInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinaMOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi’an Jiaotong University, Xi’an 710049, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinaTrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, ChinaTrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, ChinaTrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, ChinaTrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, ChinaTrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou 510632, ChinaDepartment of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USATrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, ChinaMOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi’an Jiaotong University, Xi’an 710049, ChinaTrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, ChinaMOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi’an Jiaotong University, Xi’an 710049, China; Corresponding authorInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Corresponding authorTrinomab Pharmaceutical Co., Ltd., Zhuhai 519040, China; Corresponding authorSummary: Human cytomegalovirus (hCMV) poses a severe threat to fetuses, newborns, and immunocompromised individuals. No approved vaccines and limited treatment options are current medical challenges. Here, we analyze the human B cell responses to glycoprotein B (gB) in three top hCMV neutralizers from a cohort of 283 individuals with latent-infected hCMV. By single-cell amplification of memory B cells, we identify a cluster of potent neutralizing monoclonal antibodies (nAbs) that competitively recognize an unknown vulnerable site on gB antigenic domain 5 (AD-5). This cluster of nAbs functionally outperforms the nAbs utilized in clinical trials. Cryoelectron microscopy (cryo-EM) unveils the structural basis of the neutralization mechanism of an antibody directly targeting the fusion subdomain on AD-5. Moreover, immunological analyses of human and mouse sera have preliminarily validated the potential superiority of AD-5-focused immune responses. Overall, our results will support the development of optimized gB-based vaccines and provide promising prophylactic and therapeutic antibody candidates against hCMV infection.http://www.sciencedirect.com/science/article/pii/S2211124725004176CP: ImmunologyCP: Microbiology |
| spellingShingle | Changwen Wu Nan Song Yizhen Zhao Han Wang Yuanbao Ai Yayu Wang Yueming Wang Xiaohui Yuan Tong Liu Nan Li Dabbu Kumar Jaijyan Chengming Li Lei Zhang Weihong Zheng Zhiwei Yang Shujia Zhu Hua-Xin Liao Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodies Cell Reports CP: Immunology CP: Microbiology |
| title | Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodies |
| title_full | Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodies |
| title_fullStr | Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodies |
| title_full_unstemmed | Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodies |
| title_short | Structural basis of human cytomegalovirus neutralization by gB AD-5-specific potent antibodies |
| title_sort | structural basis of human cytomegalovirus neutralization by gb ad 5 specific potent antibodies |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004176 |
| work_keys_str_mv | AT changwenwu structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT nansong structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT yizhenzhao structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT hanwang structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT yuanbaoai structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT yayuwang structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT yuemingwang structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT xiaohuiyuan structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT tongliu structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT nanli structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT dabbukumarjaijyan structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT chengmingli structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT leizhang structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT weihongzheng structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT zhiweiyang structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT shujiazhu structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies AT huaxinliao structuralbasisofhumancytomegalovirusneutralizationbygbad5specificpotentantibodies |