该课题组研究人员设计了一种表位聚焦的猿人免疫缺陷病毒（SHIV.5MUT），在22只猕猴中有14只在感染一年内引发广泛而有效的V3-聚糖靶向抗体，而14只对照动物中没有。SHIV.5MUT通过两步机制诱导了bNAbs，诱导了V1定向抗体的初始波，这些抗体选择了具有缩短的、低糖基化V1环的Envs，这反过来又引发了V3聚糖bNAb前体。恒河猴bNAbs在免疫遗传学和结构上具有多样性，与人的V3-聚糖bNAbs非常相似。Env-bNAb共同进化揭示了多种bNAb前体和使其成熟的Env变体，为疫苗设计提供了分子蓝图。
据悉，HIV-1疫苗和治疗研究面临的一个主要障碍是缺乏一种近交动物模型来快速和一致地诱导广泛中和抗体（bNAbs）。
附：英文原文
Title: Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design
Author: Ashwin N. Skelly, Harry B. Gristick, Hui Li, Edem Gavor, Andrew J. Connell, Edward F. Kreider, Lorie Marchitto, Michael P. Hogarty, Maddy L. Newby, Joel D. Allen, Weimin Liu, Anthony P. WestJr., Kasirajan Ayyanathan, Mary S. Campion, Kaitlyn Winters, Colette G. Gordon, Rebecca A. Osbaldeston, Macy J. Akeley, Emily Lewis, Yingying Li, Ajay Singh, Kendra Cruickshank, Younghoon Park, Chengyan Zhao, Xuduo Li, Khaled Amereh, Elizabeth Van Itallie, John W. Carey, Amie Albertus, Andrew T. DeLaitsch, Jennifer R. Keeffe, Melinda G. Lituchy, Agnes A. Walsh, Daniel J. Morris, Rumi Habib, Frederic Bibollet-Ruche, Nitesh Mishra, Gabriel Avillion, Nicholas S. Koranda, Samantha J. Plante, Christian L. Martella, Jinery Lora, Eric J. D. Wang, Mark G. Lewis, Malcolm A. Martin, Michel C. Nussenzweig, Michael S. Seaman, Darrell J. Irvine, Kevin J. Wiehe, Barton F. Haynes, Kshitij Wagh, Bette Korber, Raiees Andrabi, Max Crispin, Drew Weissman, Pamela J. Bjorkman, Beatrice H. Hahn, George M. Shaw
Issue&Volume: 2026-05-07
Abstract: A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.
DOI: aec6396
Source: https://www.science.org/doi/10.1126/science.aec6396