Analysis of breakthrough HIV-1 infections could elucidate whether prior vaccination primes relevant immune responses. Here, we measured HIV-specific antibody responses in 14 South African volunteers who acquired HIV infection after participating in phase 1/2 trials of envelope-containing immunogens. Serum samples were collected annually following HIV-1 infection from participants in trials HVTN 073 (subtype C, DNA/MVA, phase 1 trial, n = 1), HVTN 086 (subtype C, DNA/MVA/gp140 protein, phase 1 trial, n = 2), and HVTN 204 (multisubtype, DNA/adenovirus serotype 5 [Ad5], phase 2 trial, n = 7) and 4 placebo recipients. Binding and neutralizing antibody responses to Env proteins and peptides were determined pre- and post-HIV infection using an enzyme-linked immunosorbent assay and the TZM-bl cell neutralization assay, respectively. HIV-infected South African individuals served as unvaccinated controls. Binding antibodies to gp41, V3, V2, the membrane-proximal external region (MPER), and the CD4 binding site were detected from the first year of HIV-1 subtype C infection, and the levels were similar in vaccinated and placebo recipients. Neutralizing antibody responses against tier 1A viruses were detected in all participants, with the highest titers being to a subtype C virus, MW965.26. No responses were observed just prior to infection, indicating that vaccine-primed HIV-specific antibodies had waned. Sporadic neutralization activity against tier 2 isolates was observed after 2 to 3 years of HIV infection, but these responses were similar in the vaccinated and placebo groups as well as the unvaccinated controls. Our data suggest that prior vaccination with these immunogens did not alter the antibody responses to HIV-1 infection, nor did it accelerate the development of HIV neutralization breadth.IMPORTANCE There is a wealth of information on HIV-specific vaccine-induced immune responses among HIV-uninfected participants; however, data on immune responses among participants who acquire HIV after vaccination are limited. Here we show that HIV-specific binding antibody responses in individuals with breakthrough HIV infections were not affected by prior vaccination with HIV envelope-containing immunogens. We also found that these vectored vaccines did not prime tier 2 virus-neutralizing antibody responses, which are thought to be required for prevention against HIV acquisition, or accelerate the development of neutralization breadth. Although this study is limited, such studies can provide insights into whether vaccine-elicited antibody responses are boosted by HIV infection to acquire broader neutralizing activity, which may help to identify antigens relevant to the design of more effective vaccines.

中文翻译：

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HIV信封疫苗接种对随后的HIV感染抗体反应的影响。

对突破性HIV-1感染的分析可以阐明以前的疫苗接种是否引发相关的免疫反应。在这里，我们测量了14名南非志愿者的HIV特异性抗体应答，这些志愿者参加了包含信封的免疫原的1/2期临床试验后感染了HIV。HIV-1感染后，每年从试验HVTN 073（C型，DNA / MVA，1期试验，n = 1），HVTN 086（C型，DNA / MVA / gp140蛋白，1期试验， n = 2）和HVTN 204（多亚型，DNA /腺病毒血清型5 [Ad5]，2期试验，n = 7）和4位安慰剂接受者。在HIV感染之前和之后，分别使用酶联免疫吸附测定和TZM-bl细胞中和测定来确定对Env蛋白和肽的结合和中和抗体反应。感染艾滋病毒的南非人作为未接种疫苗的对照。从HIV-1 C亚型感染的第一年开始，检测到针对gp41，V3，V2，膜近端外部区域（MPER）和CD4结合位点的结合抗体，并且接种疫苗和安慰剂接受者的水平相似。在所有参与者中均检测到针对1A病毒的中和抗体应答，滴度最高的是C型病毒MW965.26。感染前未观察到反应，表明疫苗引发的HIV特异性抗体已经减弱。在感染艾滋病毒2至3年后，观察到了针对第2层分离株的零星中和活性，但在接种疫苗和安慰剂组以及未接种疫苗的对照组中，这些反应相似。我们的数据表明，预先接种这些免疫原不会改变对HIV-1感染的抗体反应，也不会加速HIV中和广度的发展。重要信息关于HIV特异性疫苗诱导的免疫反应的信息很多-未感染的参与者；但是，接种疫苗后感染艾滋病毒的参与者之间的免疫反应数据有限。在这里，我们显示具有突破性HIV感染的个体中的HIV特异性结合抗体反应不受先前用含HIV包膜的免疫原接种的影响。我们还发现，这些载体化疫苗并未引发2级病毒中和抗体反应，这被认为是预防HIV感染或加速中和广度发展所必需的。