Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition 机翻标题: 暂无翻译,请尝试点击翻译按钮。

来源
Journal of Medicinal Chemistry
年/卷/期
2018 / 61 / 22
页码
10116-10125
ISSN号
0022-2623
作者单位
Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA;Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA;Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA;Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA;Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA;Duke Univ, Med Ctr, Dept Surg, Durham, NC 27705 USA;Duke Univ, Med Ctr, Dept Surg, Durham, NC 27705 USA;Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA;
作者
Zhang, Rou-Shu;Cai, Hui;Orwenyo, Jared;Giddens, John;Yang, Qiang;LaBranche, Celia C.;Montefiori, David C.;Wang, Lai-Xi;
摘要
The N332 high-mannose glycan on the HIV-1 gp120 V3-loop is the target of many bNAbs. About 17% HIV isolates carry the N332 to N334 mutation, but the antibody recognition of the N334 N-glycan and its immunogenicity are not well characterized. Here we report the chemoenzymatic synthesis, antigenicity, and immunogenicity of the V3 N334 glycopeptides from HIV-1 A244 gp120, a key component in the partially successful Thai clinical trials. We found that synthetic V3 glycopeptide carrying a N334 high-mannose glycan could be recognized by bNAb PGT128 and PGT126 but not by 10-1074. Rabbit immunization with the synthetic three-component A244 glycopeptide immunogen elicited substantial glycan-dependent antibodies with broad reactivity. to various HIV-1 gp120/gp140 carrying N332 or N334 glycosylation sites. These results indicated that the N334 site is vulnerable and the A244 V3 glycopeptide represents a valuable immunogen for further HIV-1 vaccine studies.
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