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




An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene. - Download this document for free, or read online. Document in PDF available to download.

Journal Title:

Emerging Microbes and Infections

Volume:

Volume 5, Number 6

Publisher:

Nature Publishing Group: Open Access Journals - Option C | 2016-06-22, Pages e65-e65

Type of Work:

Article | Final Publisher PDF

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.

Subjects: Health Sciences, Immunology - Biology, Genetics - Biology, Molecular - Research Funding: 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 - HIV-1 - neutralizing antibody - 10E8 epitopes -



Author: Zhiwu Sun, Yun Zhu, Qian Wang, Ling Ye, Yanyan Dai, Shan Su, Fei Yu, Tianlei Ying, Chinglai Yang, Shibo Jiang, Lu Lu, Show all au

Source: https://open.library.emory.edu/



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