HIV-1疫苗免疫原设计的研究进展

Advances in the Immunogenic Design of HIV-1 Vaccine

至今,艾滋病仍是人类历史上最严重的传染病之一。设计和生产具有保护效力的预防型HIV-1疫苗一直被认为是战胜艾滋病的最佳途径。虽然经过了数十年的努力,但有效的HIV-1疫苗仍未研制成功。在进入临床试验的5种疫苗中,只有RV144实验显示出31%的保护效力,但并不能控制已感染者病情进程。通过临床实验数据和体外实验分析,目前主要有两种免疫原设计策略:诱导广谱中和抗体(bNAb)和有效的细胞毒性T淋巴细胞(CTL)应答。诱导bNAb可以阻止病毒感染或者降低感染率,其主要免疫原包括:病毒样颗粒、天然包膜蛋白三聚体和稳定的bNAb结合表位等。而诱导有效的CTL应答可以减缓病毒感染进程,其主要免疫原包括:"马赛克"疫苗、保守区免疫原和病毒适应性图谱指导的免疫原等。本文将主要阐述这两种免疫原设计策略及其研究进展。

A safe and effective vaccine against the human immunodeficiency virus type 1（HIV-1）is expected to have a considerable impact on elimination of acquired immune deficiency syndrome.Despite decades of effort,an effective vaccine against HIV-1remains elusive.In recent years,the Thai HIV Vaccine Efficacy Trial（known as RV144）showed a reduction in HIV-1acquisition by 31%,but this agent could not delay disease progression in vaccinated individuals.Clinical analyses of experimental data and experiments in vitro have revealed two main types of immunogen design：induction of broad-spectrum neutralizing antibody（bNAb）and cytotoxic T lymphocyte（CTL）responses.bNAb can prevent or reduce acquisition of infection,and its main immunogens are virus-like particles,natural envelope trimers and stable bNAb epitopes.An effective CTL response can slow-down viral infection,and its main immunogens are＂mosaic＂vaccines,＂conserved immunogens＂,and the＂fitness landscape＂of HIV-1proteins.This review summarizes the strategies as well as progress in the design and testing of HIV-1immunogens to elicit bNAb and CTL responses.