合成 HIV V3 糖肽免疫原携带 N334 N-聚糖诱导具有广泛识别表位的糖依赖性抗体。
Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition.
机构信息
Department of Chemistry and Biochemistry , University of Maryland , College Park , Maryland 20742 , United States.
Department of Surgery , Duke University Medical Center , Durham , North Carolina 27705 , United States.
出版信息
J Med Chem. 2018 Nov 21;61(22):10116-10125. doi: 10.1021/acs.jmedchem.8b01290. Epub 2018 Nov 8.
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.
HIV-1 gp120 V3 环上的 N332 高甘露糖聚糖是许多 bNAb 的靶标。约 17%的 HIV 分离株携带 N332 到 N334 突变，但对 N334 N-聚糖的抗体识别及其免疫原性尚未得到很好的描述。在这里，我们报告了来自 HIV-1 A244 gp120 的 V3 N334 糖肽的化学酶合成、抗原性和免疫原性，A244 gp120 是部分成功的泰国临床试验中的关键成分。我们发现，携带 N334 高甘露糖聚糖的合成 V3 糖肽可被 bNAb PGT128 和 PGT126 识别，但不能被 10-1074 识别。用合成的三组分 A244 糖肽免疫原对兔进行免疫接种，可诱导出大量依赖聚糖的抗体，对携带 N332 或 N334 糖基化位点的各种 HIV-1 gp120/gp140 具有广泛的反应性。这些结果表明，N334 位点是脆弱的，A244 V3 糖肽代表了进一步 HIV-1 疫苗研究的有价值的免疫原。
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