小柯机器人

美国斯克利普斯研究所William R. Schief等研究人员合作实现，非人灵长类中罕见艾滋病毒广泛中和抗体前体的疫苗启动。该项研究成果发表在2024年5月17日出版的《科学》杂志上。

研究人员表示，种系靶向免疫原有望诱导出针对艾滋病毒和其他病原体的广泛中和抗体（bnAb）。然而，抗体与抗原的识别通常是由重链互补决定区3（HCDR3）的相互作用主导的，种系靶向免疫原对HCDR3主导的bnAb疫苗诱导尚未在人类或远系繁殖动物中得到证实。

研究人员用N332-GT5（一种设计用于靶向HCDR3显性bnAb BG18前体的HIV包膜三聚体）进行免疫接种，8只猕猴中有8只的bnAb前体B细胞得到了大量接种，并在生发中心和记忆B细胞中形成了不同的谱系。研究人员用冷冻电镜证实了bnAb拟态、HCDR3主导、三聚体结合的相互作用。这些研究结果证明了HCDR3主导的bnAb-前体活化在远系繁殖动物中的原理，并表明N332-GT5有望在人类中诱导类似的反应。

附：英文原文

Title: Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

Author: Jon M. Steichen, Ivy Phung, Eugenia Salcedo, Gabriel Ozorowski, Jordan R. Willis, Sabyasachi Baboo, Alessia Liguori, Christopher A. Cottrell, Jonathan L. Torres, Patrick J. Madden, Krystal M. Ma, Henry J. Sutton, Jeong Hyun Lee, Oleksandr Kalyuzhniy, Joel D. Allen, Oscar L. Rodriguez, Yumiko Adachi, Tina-Marie Mullen, Erik Georgeson, Michael Kubitz, Alison Burns, Shawn Barman, Rohini Mopuri, Amanda Metz, Tasha K. Altheide, Jolene K. Diedrich, Swati Saha, Kaitlyn Shields, Steven E. Schultze, Melissa L. Smith, Torben Schiffner, Dennis R. Burton, Corey T. Watson, Steven E. Bosinger, Max Crispin, John R. YatesIII, James C. Paulson, Andrew B. Ward, Devin Sok, Shane Crotty, William R. Schief

Issue&Volume: 2024-05-17

Abstract: Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo–electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

DOI: adj8321

Source: https://www.science.org/doi/10.1126/science.adj8321