一种保护性的HIV疫苗将需要在人体内诱导广泛中和抗体（bnAbs），但是启动罕见的bnAb前体B细胞一直具有挑战性。在一项双盲、安慰剂对照的1期人体临床试验中，重组种系靶向包膜糖蛋白（Env）三聚体BG505 SOSIP.v4.1-GT1.1在AS01B佐剂下，在大多数疫苗接受者中高频率地诱导VRC01类bnAb前体。这些靶向CD4受体结合位点的bnAb前体经历了VRC01类的体细胞超突变特征。分离的VRC01类单克隆抗体亚群中和野生型假病毒主题，在结构上与bnAb VRC01极其相似。这些结果进一步支持了人类HIV疫苗设计的种系靶向方法，并证明了合理的疫苗设计可以在原子水平上操纵B细胞反应。
附：英文原文
Title: Precise targeting of HIV broadly neutralizing antibody precursors in humans
Author: Tom G. Caniels, Madhu Prabhakaran, Gabriel Ozorowski, Kellie J. MacPhee, Weiwei Wu, Karlijn van der Straten, Sashank Agrawal, Ronald Derking, Emma I. M. M. Reiss, Katrina Millard, Martina Turroja, Aimee Desrosiers, Jeffrey Bethony, Elissa Malkin, Marinus H. Liesdek, Annelou van der Veen, Michelle Klouwens, Jonne L. Snitselaar, Joey H. Bouhuijs, Rhianna Bronson, Jalen Jean-Baptiste, Suprabhath Gajjala, Zahra Rikhtegaran Tehrani, Alison Benner, Mukundhan Ramaswami, Michael O. Duff, Yung-Wen Liu, Alicia H. Sato, Ju Yeong Kim, Isabel J. L. Baken, Catarina Mendes Silva, Tom P. L. Bijl, Jacqueline van Rijswijk, Judith A. Burger, Albert Cupo, Anila Yasmeen, Swastik Phulera, Wen-Hsin Lee, Kipchoge N. RandallJr., Shiyu Zhang, Martin M. Corcoran, Isabel Regadas, Alex C. Sullivan, David M. Brown, Jennifer A. Bohl, Kelli M. Greene, Hongmei Gao, Nicole L. Yates, Sheetal Sawant, Jan M. Prins, Neeltje A. Kootstra, Stephen M. Kaminsky, Burc Barin, Farhad Rahaman, Margaret Meller, Vince Philiponis, Dagna S. Laufer, Angela Lombardo, Lindsey Mwoga, Solmaz Shotorbani, Drienna Holman, Richard A. Koup, Per Johan Klasse, Gunilla B. Karlsson Hedestam, Georgia D. Tomaras, Marit J. van Gils, David C. Montefiori, Adrian B. McDermott, Ollivier Hyrien, John P. Moore, Ian A. Wilson, Andrew B. Ward, David J. Diemert, Godelieve J. de Bree, Sarah F. Andrews, Marina Caskey, Rogier W. Sanders
Issue&Volume: 2025-05-15
Abstract: A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01B, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, that target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.
DOI: adv5572
Source: https://www.science.org/doi/10.1126/science.adv5572