Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
PLoS One. 2011;6(7):e22010. doi: 10.1371/journal.pone.0022010. Epub 2011 Jul 20.
A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.
需要一种安全、有效的疫苗来阻止艾滋病大流行。STEP 试验令人失望的结果表明需要包括体液抗 HIV-1 反应，这一概念得到了 RV144 试验数据的支持，尽管保护相关因素尚不清楚。我们用重组猿猴免疫缺陷病毒（SIV）Gag-Pol 颗粒、HIV-1 Tat 和三聚体 C 型（HIV-C）gp160 对恒河猴进行了疫苗接种，这些疫苗诱导了交叉中和抗体（nAbs）和强大的细胞免疫反应。在五次低剂量粘膜挑战用编码异源 R5 HIV-C 包膜的猿猴-人免疫缺陷病毒（SHIV）后（与 gp160 免疫原的 22.1%差异），94%的对照组出现病毒血症，而三分之一的疫苗接种者保持无病毒血症。在高剂量 SHIV 再挑战时，所有对照组均被感染，而一些疫苗接种者仍保持无病毒血症。病毒血症峰值与细胞免疫（p<0.001）和交叉 nAb 滴度（p<0.001）呈负相关。这些数据首次将细胞免疫和体液免疫反应与保护程度联系起来。
