Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Curr Opin HIV AIDS. 2023 Nov 1;18(6):290-299. doi: 10.1097/COH.0000000000000821. Epub 2023 Sep 13.
In the past two decades, there has been an explosion in the discovery of HIV-1 broadly neutralizing antibodies (bnAbs) and associated vaccine strategies to induce them. This abundance of approaches necessitates a system that accurately and expeditiously identifies the most promising regimens. We herein briefly review the background science of bnAbs, provide a description of the first round of phase 1 discovery medicine studies, and suggest an approach to integrate these into a comprehensive HIV-1-neutralizing vaccine.
With recent preclinical success including induction of early stage bnAbs in mouse knockin models and rhesus macaques, successful priming of VRC01-class bnAbs with eOD-GT8 in a recent study in humans, and proof-of-concept that intravenous infusion of VRC01 prevents sexual transmission of virus in humans, the stage is set for a broad and comprehensive bnAb vaccine program. Leveraging significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, the HVTN has reconfigured its HIV-1 vaccine strategy by developing the Discovery Medicine Program to test promising vaccine candidates targeting six key epitopes.
The HVTN Discovery Medicine program is testing multiple HIV-1-neutralizing vaccine candidates.
目的综述：在过去的二十年中，HIV-1 广谱中和抗体（bnAbs）的发现以及相关的疫苗策略呈爆炸式增长，旨在诱导产生这些抗体。大量的方法需要一个系统来准确、迅速地识别最有前途的方案。本文简要回顾了 bnAbs 的背景科学，描述了首轮发现医学研究，并提出了一种将这些方法整合到全面的 HIV-1 中和疫苗中的方法。
最新发现：最近的临床前研究取得了成功，包括在小鼠基因敲入模型和恒河猴中诱导早期 bnAbs，以及在最近的一项人类研究中 eOD-GT8 成功地对 VRC01 类 bnAbs 进行了初步免疫，证明静脉注射 VRC01 可预防人类的性传播病毒，为广泛而全面的 bnAb 疫苗计划奠定了基础。利用蛋白质纳米颗粒科学、mRNA 技术、佐剂开发以及 B 细胞和抗体分析方面的重大进展，HVTN 通过开发发现医学计划来测试针对六个关键表位的有前途的候选疫苗，重新配置了其 HIV-1 疫苗策略。
总结：HVTN 发现医学计划正在测试多种 HIV-1 中和疫苗候选物。
