一项HIV-1疫苗有效性试验的免疫相关因素分析

巴顿·F·海恩斯等 美国北卡罗来纳达勒姆杜克大学医学院、杜克大学人类疫苗研究所和人类免疫缺陷病毒/艾滋病（HIV/AIDS）疫苗免疫中心等

背景 在RV144探索性试验中，一种针对1型人类免疫缺陷病毒（HIV-1）的疫苗方案的估计有效性为31.2%。我们进行了一项病例-对照分析，以辨别与感染危险相关的抗体和细胞免疫。

BACKGROUND In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 （HIV-1） was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk.

方法 在采用RV144血样进行的初步研究中，有17种抗体或细胞检测满足预先规定的标准，选择了其中6种作为确定T细胞、IgG抗体和IgA抗体反应在调节感染风险中的作用。对来自41名被感染的接种疫苗者及205名未被感染的疫苗接种者的样本（样本在末次接种2周后采集）进行了检测，以评估免疫-应答变量是否可预测42个月随访期间（发生）的HIV-1感染。

METHODS In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up.

结果 在6种主要变量中，2种与感染风险明显相关：IgG抗体和HIV-1包膜蛋白（Env）可变区1及2（V1V2）的结合与HIV-1感染率呈负相关[估计比值比为0.57（每增加1个标准差），P=0.02，q=0.08]，血浆IgA抗体和Env的结合与感染率直接相关[估计比值比为1.54（每增加1个标准差），P=0.03，q=0.08]。低水平的V1V2抗体和高水平的Env特异性IgA抗体均不与较高的感染率（高于安慰剂组中发现的）相关。次要分析提示，Env特异性IgA抗体可能削弱具有潜在保护作用抗体的效应。

RESULTS Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 （V1V2） of HIV-1 envelope proteins （Env） correlated inversely with the rate of HIV-1 infection （estimated odds ratio, 0.57 per 1-SD increase; P = 0.02; q = 0.08）, and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection （estimated odds ratio, 1.54 per 1-SD increase; P = 0.03; q = 0.08）. Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Envspecific IgA antibodies may mitigate the effects of potentially protective antibodies.

结论 免疫相关因素的研究形成了一个假说，即V1V2抗体可能对HIV-1感染具有保护作用，而高水平的Env特异性IgA抗体则可能削弱了保护性抗体的作用。设计比RV144疫苗诱导出更高水平的V1V2抗体及更低水平的Env特异性IgA抗体的疫苗，可能提高了针对HIV-1感染的有效性。

CONCLUSIONS This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Envspecific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection.