Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2

摘要

The RV144 trial demonstrated 31% vaccine efficacy at preventing human immunodeficiency virus (HIV)-1 infection. Antibodies against the HIV-1 envelope variable loops 1 and 2 (Env VI and V2) correlated inversely with infection risk. We proposed that vaccine-induced immune responses against V1/V2 would have a selective effect against, or sieve, HIV-1 breakthrough viruses. A total of 936 HIV-1 genome sequences from 44 vaccine and 66 placebo recipients were examined. We show that vaccine-induced immune responses were associated with two signatures in V2 at amino acid positions 169 and 181. Vaccine efficacy against viruses matching the vaccine at position 169 was 48% (confidence interval 18% to 66%; P= 0.0036), whereas vaccine efficacy against viruses mismatching the vaccine at position 181 was 78% (confidence interval 35% to 93%; P= 0.0028). Residue 169 is in a cationic glycosylated region recognized by broadly neutralizing and RV144-derived antibodies. The predicted distance between the two signature sites (21 ± 7 A) and their match/mismatch dichotomy indicate that multiple factors may be involved in the protection observed in RV144. Genetic signatures of RV144 vaccination in V2 complement the finding of an association between high Vl/ V2-binding antibodies and reduced risk of HIV-1 acquisition, and provide evidence that vaccine-induced V2 responses plausibly had a role in the partial protection conferred by the RV144 regimen.%涉及超过16,1ooo志愿者的一项重大临床试rn验(被称为RV144试验),测试了两种疫苗rn(ALVAC-HIV和AIDSVAX B/E gp120)的组合防rn止HIV感染的能力及其安全性。该疫苗组会对rnHIV-1感染31％有效，针对HIV-1的抗体包裹着rn与感染风险逆相关的“可变环-1和2(V1/V2)”rn域。Rolland等人对RV144试验参加者的突破rn性感染做了遗传分析，识别出了与疫苗诱导的rn免疫压力相关的特征，从而为免疫与保护之间rn的因果关系提供了支持。病毒包膜第二个可变rn环的169位置和181位置上的病毒氨基酸变化rn被发现与免疫效果关系最大，是未来疫苗的一rn个可能目标。