近日，美国Wistar研究所教授Amelia Escolano及其小组在非人灵长类动物中快速诱导针对HIV-1 Env V3聚糖表位的中和Asn332聚糖非依赖性抗体。这一研究成果发表在2026年2月3日出版的国际学术期刊《自然—免疫学》上。

该课题组人员提出了WIN332，一种新的工程Env免疫原，可诱导一类新的不依赖Asn332 -聚糖的抗体到Env保守的 V3-聚糖表位，具有低抑制活性，表明在非人灵长类动物单次免疫后具有中和活性。WIN332结合典型的人Asn332 -聚糖依赖性（Ⅰ型）V3 -聚糖bNAb的前体，也结合同类中首个Asn332 -聚糖非依赖性（Ⅱ型）V3 -聚糖bNAb的前体。单次免疫引起低抑制血清和单克隆抗体，这些抗体与异源免疫原增强和亲和力成熟。血清抗体的电镜多克隆表位定位分析、抗体克隆和低温电镜分析显示，WIN332诱导出与Asn332 -甘聚糖无关的抗体，其序列和结合与最有效的人Ⅰ型和Ⅱ型V3 -甘聚糖bNAb具有惊人的相似性。因此，WIN332是一种很有前途的疫苗候选物，可以简化V3-glycan bNAb的激发。

研究人员表示，序贯免疫是一种很有前途的方法，可引发针对HIV-1包膜（Env）的广泛中和抗体（bNAbs）。然而，现有的方案效率低下，而且涉及长时间的多次免疫接种。

附：英文原文

Title: Rapid elicitation of neutralizing Asn332-glycan-independent antibodies to the V3-glycan epitope of HIV-1 Env in nonhuman primates

Author: Relano-Rodriguez, Ignacio, Du, Jianqiu, Lin, Zi Jie, Kerwin, Margaret, Tarquis-Medina, Marta, Urbano, Eduardo, Cui, Jiayan, Watkins, Meagan, Lavine, Christy L., Zhao, Peng, Habib, Rumi, Agostino, Colby, Ghosh, Sukanya, Park, Joyce, Boroughs, Caroline, Walsh, Agnes A., Melo, Mariane B., Shukla, Niharika, Shaw, George M., Hahn, Beatrice H., Irvine, Darrell J., Wells, Lance, Weiner, David B., Seaman, Michael S., Kulp, Daniel W., Veazey, Ronald S., Pallesen, Jesper, Escolano, Amelia

Issue&Volume: 2026-02-03

Abstract: Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. Here, we present WIN332, a new engineered Env immunogen that induces a new class of Asn332-glycan-independent antibodies to the conserved V3-glycan epitope of Env with low inhibitory activity indicative of a neutralization activity after a single bolus immunization in nonhuman primates. WIN332 binds to precursors of canonical human Asn332-glycan-dependent (type-I) V3-glycan bNAbs but also of a first-of-its-class Asn332-glycan-independent (type-II) V3-glycan bNAb. A single immunization elicits low inhibitory serum and monoclonal antibodies that are boosted and affinity matured with a heterologous immunogen. Electron microscopy polyclonal epitope mapping analysis of serum antibodies, antibody cloning and cryogenic electron microscopy analysis reveals that WIN332 elicits Asn332-glycan-independent antibodies with striking sequence and binding similarities with the most potent human type-I and type-II V3-glycan bNAbs. Thus, WIN332 is a promising vaccine candidate to streamline V3-glycan bNAb elicitation.

DOI: 10.1038/s41590-025-02408-z

Source: https://www.nature.com/articles/s41590-025-02408-z