10E8-like neutralizing antibodies against HIV-1 induced using a precisely designed conformational peptide as a vaccine prime

作     者：YU Yang TONG Pei LI Yu LU ZhiFeng CHEN YingHua 

作者机构：Laboratory of Immunology School of Life Sciences Tsinghua University Beijing Key Laboratory for Protein Therapeutics MOE Key Laboratory for Protein Sciences 

基　　金：supported by Ministry of Science and Technology of China(2012ZX10001-009) 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2014年第57卷第1期

页      码：117-127页

摘      要：Recent studies have demonstrated that the membrane-proximal external region （MPER） of human immunodeficiency virus 1 （HIV-1） glycoprotein 41 contains a series of epitopes for human monoclonal antibodies, including 2F5, Zl3el, 4El0, and 10E8, which were isolated from HIV-l-infected individuals and show broad neutralizing activities. This suggests that MPER is a good target for the development of effective HIV-1 vaccines. However, many studies have shown that it is difficult to induce antibodies with similar broad neutralizing activities using MPER-based peptide antigens. Here, we report that 10E8-1ike neu- tralizing antibodies with effective anti-HIV-1 activity were readily induced using a precisely designed conformational immu- nogenic peptide containing the 10E8-specific epitope. This immunogenic peptide （designated T10HE） contains a 15-mer MPER-derived 10E8-specific epitope fused to T-helper-cell epitopes from tetanus toxin （tt）, which showed a significantly sta- bilized a-helix structure after a series of modifications, including substitution with an （S）-c^-（2＇-pentenyl） alanine containing an olefin-bearing tether and ruthenium-catalyzed olefin metathesis, compared with the unmodified T10E peptide. The stabilized （x-helix structure of T10HE did not affect its capacity to bind the 10E8 antibody, as evaluated with an enzyme linked immuno- sorbent assay （ELISA） and surface plasmon resonance binding assay （SPR assay）. The efficacies of the T10HE and T10E epitope vaccines were evaluated after a standard vaccination procedure in which the experimental mice were primed with ei- ther the T10HE or T10E immunogen and boosted with HIV-1 JRFL pseudoviruses. Higher titers of 10E8-1ike antibodies were induced by T10HE than that by T10E. More importantly, the antibodies induced by T10HE showed enhanced antiviral potency against HIV-1 strains with both X4 and R5 tropism and a greater degree of broad neutralizing activity than the antibodies in- duced by T10E. These results indic

主 题 词：MPER peptide immunogen vaccine prime neutralizing antibody 

学科分类：1001[医学-基础医学] 100102[100102] 10[医学] 

核心收录：

D　O　I：10.1007/s11427-013-4591-0

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