疫苗接种产生广泛的交叉中和抗体HIV Env顶点，这一成果由美国斯克里普斯研究所Richard T. Wyatt研究组经过不懈努力而取得。相关论文于2026年4月29日发表在《自然》杂志上。

在这里，研究组确定了一种疫苗接种策略，将异源性HIV Env三聚体共价偶联到脂质体上进行多价展示，从而在所有三聚体脂质体免疫的非人灵长类动物中引发交叉中和的HIV血清抗体反应。关键的是，小组从多个猕猴中分离出单克隆抗体，交叉中和不同的HIV临床分离物。来自不同猕猴的单克隆抗体的高分辨率低温电镜结构分析表明，它们以高度类似于人类感染引发的、指向顶点的广泛中和抗体PG9的方式靶向Env三聚体顶点，这代表了HIV疫苗开发的重大进展。

据介绍，作为一种慢性复制病毒，HIV进化出了极端的序列变异性，并通过宿主衍生的聚糖有效地屏蔽了功能受限的刺突蛋白决定因子。广泛中和抗体虽然罕见，但可以从HIV感染者中分离出来，揭示保守的包膜糖蛋白（Env）位点是疫苗开发的关键靶点。一个这样的目标是Env尖峰的顶点。

附：英文原文

Title: Vaccination generates broadly cross-neutralizing antibodies to the HIV Env apex

Author: Guenaga, Javier, dori, Monika, Bale, Shridhar, Phulera, Swastik, Zygouras, Ioannis, Schleich, Fabian-Alexander, Castro Dopico, Xaquin, Agrawal, Sashank, Ota, Miyo, Wilson, Richard, Cluff, Jocelyn, Dzvelaia, Tamar, Mandolesi, Marco, Lee, Wen-Hsin, Walsh, Agnes A., Melo, Mariane B., Verkoczy, Laurent, Irvine, Darrell J., Corcoran, Martin, Wilson, Ian A., Carnathan, Diane, Silvestri, Guido, Ward, Andrew B., Ozorowski, Gabriel, Karlsson Hedestam, Gunilla B., Wyatt, Richard T.

Issue&Volume: 2026-04-29

Abstract: As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans1. Broadly neutralizing antibodies, although rare, can be isolated from people living with HIV, revealing conserved envelope glycoprotein (Env) sites as key targets for vaccine development2,3,4. One such target is the apex of the Env spike. Here we identify a vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display that resulted in the elicitation of cross-neutralizing HIV serum antibody responses in all trimer-liposome-immunized non-human primates. Critically, we isolated monoclonal antibodies from multiple macaques that cross-neutralize divergent HIV clinical isolates. High-resolution cryogenic electron microscopy structural analyses of monoclonal antibodies from four different macaques demonstrate that they target the Env trimer apex in a manner highly similar to that of the human-infection-elicited, apex-directed broadly neutralizing antibody PG9, representing a substantial advance in HIV vaccine development.

DOI: 10.1038/s41586-026-10429-3

Source: https://www.nature.com/articles/s41586-026-10429-3