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

摘要：HIV疫苗所研究的免疫原设计主要针对HIV包膜蛋白进行,其gp41近膜端(Membrane-proximal external region,mper)被证实是高度保守的线性表位。已报道的广谱中和抗体2F5、4E10及10E8靶向于该表位,但由于mper自身免疫原性较差,为提高其免疫原性、更好激起机体体液免疫反应等考虑,进行mper免疫原的设计以获得类似广谱中和抗体成为HIV-1研究的热点之一。本文对近年来mper表位的研究及其免疫原的设计进行系统的综述,为后续在艾滋疫苗免疫原的设计上提供思路。