HIV-1 envelope glycoproteins gp120 and gp41 are presented on the virus surface as a trimer of heterodimer and are the targets of broadly neutralizing antibodies (bNAbs). We describe here the synthesis and preliminary immunological evaluation of a three-component trivalent HIV-1 V3 glycopeptide immunogen aiming to raise glycopeptide epitope-specific antibodies. Click chemistry confers efficient synthesis of the lipopeptide-glycopeptide conjugate that carries three copies of HIV-1 JR-FL gp120 V3 glycopeptide with a high-mannose glycan at the N332 glycosylation site. We found that the multivalent presentation substantially enhanced the immunogenicity of the V3 glycopeptide. The antisera induced by the three-component multivalent glycopeptide immunogen exhibited stronger binding to heterologous HIV-1 gp120s and the trimeric gp140s than that from the monovalent glycopeptide immunogen. The antisera generated from this preliminary rabbit immunization did not show virus neutralization activity, probably due to the lack of somatic maturation. The ability to elicit substantial glycopeptide epitope-specific antibodies by the three-component trivalent glycopeptide immunogen suggests that it could serve as a valuable vaccine component in combination with other vaccine candidates for further immunization studies.

中文翻译：

---

多价抗原呈递增强了合成的三成分HIV-1 V3糖肽疫苗的免疫原性。

HIV-1包膜糖蛋白gp120和gp41作为异二聚体的三聚体存在于病毒表面，是广泛中和抗体（bNAbs）的目标。我们在这里描述了旨在提高糖肽表位特异性抗体的三组分三价HIV-1 V3糖肽免疫原的合成和初步免疫学评估。Click化学赋予脂肽-糖肽缀合物有效的合成，其在N332糖基化位点携带具有高甘露糖聚糖的HIV-1 JR-FL gp120 V3糖肽的三个拷贝。我们发现多价呈递大大增强了V3糖肽的免疫原性。与单价糖肽免疫原相比，三组分多价糖肽免疫原诱导的抗血清表现出与异源HIV-1 gp120s和三聚体gp140s的更强结合。此初步兔免疫产生的抗血清未显示病毒中和活​​性，可能是由于缺乏体细胞成熟。通过三组分三价糖肽免疫原引发大量糖肽表位特异性抗体的能力表明，它可以与其他疫苗候选物一起用作有价值的疫苗组分，用于进一步的免疫研究。