Eliciting broadly neutralizing antibody (bNAb) responses against HIV-1 is a major goal for a prophylactic HIV-1 vaccine. One approach is to design immunogens based on known broadly neutralizing epitopes. Here we report the design and synthesis of an HIV-1 glycopeptide immunogen derived from the V3 domain. We performed glycopeptide epitope mapping to determine the minimal glycopeptide sequence as the epitope of V3-glycan-specific bNAbs PGT128 and 10-1074. We further constructed a self-adjuvant three-component immunogen that consists of a 33-mer V3 glycopeptide epitope, a universal T helper epitope P30, and a lipopeptide (Pam3CSK4) that serves as a ligand of Toll-like receptor 2. Rabbit immunization revealed that the synthetic self-adjuvant glycopeptide could elicit substantial glycan-dependent antibodies that exhibited broader recognition of HIV-1 gp120s than the non-glycosylated V3 peptide. These results suggest that the self-adjuvant synthetic glycopeptides can serve as an important component to elicit glycan-specific antibodies in HIV vaccine design.

中文翻译：

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合成的三成分HIV-1 V3糖肽免疫原诱导糖依赖抗体的反应。

消除针对HIV-1的广泛中和抗体（bNAb）反应是预防性HIV-1疫苗的主要目标。一种方法是基于已知的广泛中和表位设计免疫原。在这里，我们报告从V3域衍生的HIV-1糖肽免疫原的设计和合成。我们进行糖肽表位作图，以确定最小的糖肽序列作为V3-聚糖特异性bNAbs PGT128和10-1074的表位。我们进一步构建了一种自佐剂三组分免疫原，由三聚体V3糖肽表位，通用T辅助表位P30和脂肽（Pam3CSK4）组成，该肽充当Toll样受体2的配体。兔免疫后发现，合成的自佐剂糖肽可以引发大量的糖依赖性抗体，与非糖基化的V3肽相比，该抗体对HIV-1 gp120s的识别范围更广。这些结果表明，自佐剂合成糖肽可以作为引发HIV疫苗设计中聚糖特异性抗体的重要成分。