HCMV enters cells primarily through glycoprotein B (gB)-mediated membrane fusion. Several neutralizing antibodies against different epitopes of gB have been isolated. Here, we report neoepitopes on antigenic domain I (AD-5) of gB revealed by study of a group of novel potent neutralizing monoclonal antibodies (mAbs). Electron micrographs and site-directed mutagenesis demonstrated that residues (N208, L213 and Y226) are the key sites for neoepitopes, which localize to the fusion subdomain of AD-5, spatially close to the fusion loops of gB. Glycosylation studies showed that these mAbs binding is independent of the glycans of gB protein. Functionally, these mAbs mainly interfere with viral membrane fusion rather than viral adhesion to cell. Moreover, sera from gBAD-5-immunized mice exhibited better antiviral efficacy than gBECD-immunization sera. Overall, our results reconstruct the antigenic profile of AD-5 and provide scientific basis for the optimal design of gB-based vaccine, especially those that focus the immune response on AD-5.
Wu, Changwen and Ai, Yuanbao and Wang, Yayu and Wang, Yueming and Liu, Tong and Zhao, Yizhen and Zan, Lipeng and Li, Nan and Yuan, Xiaohui and Li, Chengming and Yang, Zhiwei and Zhang, Shengli and Zheng, Weihong and Zhang, Lei and Liao, Hua-Xin, Novel Potent Neutralizing Antibodies Revealed the Domain I of HCMV Glycoprotein B for Vaccine Design. Available at SSRN: https://ssrn.com/abstract=3800383 or http://dx.doi.org/10.2139/ssrn.3800383
This version of the paper has not been formally peer reviewed.
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