An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene.

• Type of Material: Article
• Authors: Zhiwu Sun, Fudan University; Yun Zhu, Chinese Academy of Sciences; Qian Wang, Fudan University; Ling Ye, Emory University; Yanyan Dai, Fudan University; Shan Su, Fudan University; Fei Yu, Fudan University; Tianlei Ying, Fudan University; Chinglai Yang, Emory University; Shibo Jiang, Fudan University; Lu Lu, Fudan University
• Language: English
• Date: 2016-06-22
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Shanghai Shangyixun Cultural Communication Co., Ltd
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/emi.2016.86
• Title of Journal or Parent Work: Emerging Microbes and Infections
• ISSN: 2222-1751
• Volume: 5
• Issue: 6
• Start Page: e65
• End Page: e65
• Grant/Funding Information: This study was supported by funding from Hi-Tech Research and Development Program of China (863 Program) (2015AA020930 to LL), the National Natural Science Foundation of China (81361120378 and 81590762 to SJ, and 81373456 to LL), the Shanghai Rising-Star Program (16QA1400300 to LL) and the National Institutes of Health of the United States (1R01AI111851 to CY).
• Keywords: ADCC; neutralizing antibody; HIV-1; 10E8 epitopes
• Research Categories: Health Sciences, Immunology; Biology, Molecular; Biology, Genetics

Abstract

After three decades of intensive research efforts, an effective vaccine against HIV-1 remains to be developed. Several broadly neutralizing antibodies to HIV-1, such as 10E8, recognize the membrane proximal external region (MPER) of the HIV-1 gp41 protein. Thus, the MPER is considered to be a very important target for vaccine design. However, the MPER segment has very weak immunogenicity and tends to insert its epitope residues into the cell membrane, thereby avoiding antibody binding. To address this complication in vaccine development, we herein designed a peptide, designated 10E8-4P, containing four copies of the 10E8 epitope as an immunogen. As predicted by structural simulation, 10E8-4P exhibits a well-arranged tandem helical conformation, with the key residues in the 10E8 epitope oriented at different angles, thus suggesting that some of these key residues may be exposed outside of the lipid membrane. Compared with a peptide containing a single 10E8 epitope (10E8-1P), 10E8-4P not only exhibited better antigenicity but also elicited neutralizing antibody response against HIV-1 pseudoviruses, whereas 10E8-1P could not induce detectable neutralizing antibody response. Importantly, antibodies elicited by 10E8-4P also possessed a strong ability to activate an antibody-dependent cell-mediated cytotoxicity (ADCC) reporter gene, thus suggesting that they may have ADCC activity. Therefore, this strategy shows promise for further optimization and application in future HIV-1 vaccine design.