Immune-correlates analysis of an HIV-1 vaccine efficacy trial.
Immune-correlates analysis of an HIV-1 vaccine efficacy trial.
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HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
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发表时间：
2012-04-05
期刊：
影响因子：
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通讯作者：
Kim JH
中科院分区：
文献类型：
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作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
在RV144试验中，针对人类免疫缺陷病毒1型（HIV-1）的疫苗方案的估计有效性为31.2%。我们进行了病例对照分析，以确定感染风险的抗体和细胞免疫相关因素。在对RV144血液样本进行的初步研究中，17种抗体或细胞分析符合预先规定的标准，其中6种被选中进行初步分析，以确定t细胞、IgG抗体和IgA抗体反应在调节感染风险中的作用。对41名感染的疫苗接种者和205名未感染的疫苗接种者的样本进行了检测，这些样本是在最终免疫接种后2周获得的，通过42个月的随访来评估免疫反应变量是否预测HIV-1感染。在6个主要变量中，有2个与感染风险显著相关：IgG抗体结合HIV-1包膜蛋白（Env）可变区1和可变区2 （V1V2）与HIV-1感染率呈负相关（估计比值比为0.57 / 1- sd增加；P = 0.02; q = 0.08），血浆IgA抗体结合Env与感染率直接相关（估计比值比为1.54 / 1- sd增加；P = 0.03; q = 0.08）。与安慰剂组相比，低水平的V1V2抗体和高水平的env特异性IgA抗体均与较高的感染率无关。二次分析表明，env特异性IgA抗体可能减轻潜在保护性抗体的作用。这项与免疫相关的研究产生了V1V2抗体可能有助于预防HIV-1感染的假设，而高水平的env特异性IgA抗体可能减轻了保护性抗体的作用。与RV144疫苗相比，设计用于诱导更高水平的V1V2抗体和更低水平的env特异性IgA抗体的疫苗可能具有更好的抗HIV-1感染的功效。
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. 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. 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 Env-specific IgA antibodies may mitigate the effects of potentially protective antibodies. This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific 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.