A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected pregnant women could enhance autologous virus neutralization and thereby reduce this risk of vertical HIV transmission. Here, we assessed autologous virus NAb responses in maternal plasma samples obtained from AIDS Vaccine Evaluation Group (AVEG) protocols 104 and 102, representing historical phase I safety and immunogenicity trials of recombinant HIV Env subunit vaccines administered to HIV-infected pregnant women (ClinicalTrials registration no. NCT00001041). Maternal HIV Env-specific plasma binding and neutralizing antibody responses were characterized before and after vaccination in 15 AVEG 104 (n = 10 vaccine recipients, n = 5 placebo recipients) and 2 AVEG 102 (n = 1 vaccine recipient, n = 1 placebo recipient) participants. Single-genome amplification (SGA) was used to obtain HIV env gene sequences of autologous maternal viruses for pseudovirus production and neutralization sensitivity testing in pre- and postvaccination plasma of HIV-infected pregnant vaccine recipients (n = 6 gp120, n = 1 gp160) and placebo recipients (n = 3). We detected an increase in Env subunit MN gp120-specific IgG binding in the group of vaccine recipients between the first immunization visit and the last visit at delivery (P = 0.027, 2-sided Wilcoxon test). While no difference was observed in the levels of autologous virus neutralization potency between groups, in both groups maternal plasma collected at delivery more effectively neutralized autologous viruses from early pregnancy than late pregnancy. Immunization strategies capable of further enhancing these autologous virus NAb responses in pregnant women will be important to block vertical transmission of HIV.

中文翻译：

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在孕产妇艾滋病毒疫苗试验中诱导针对自体病毒的中和反应。


一种能够增强针对感染艾滋病毒的孕妇体内循环病毒的中和抗体（NAb）反应的母体疫苗，可以有效减少艾滋病毒的母婴传播。然而，尚不清楚对受感染的孕妇注射艾滋病毒包膜（Env）疫苗是否可以增强自体病毒中和作用，从而降低艾滋病毒垂直传播的风险。在这里，我们评估了从艾滋病疫苗评估组 (AVEG) 方案 104 和 102 获得的母体血浆样本中的自体病毒 NAb 反应，代表了对感染 HIV 的孕妇施用重组 HIV Env 亚单位疫苗的历史 I 期安全性和免疫原性试验（临床试验注册）编号：NCT00001041）。在 15 名 AVEG 104（ n = 10 名疫苗接受者， n = 5 名安慰剂接受者）和 2 名 AVEG 102（ n = 1 名疫苗接受者， n = 1 名安慰剂接受者）接种疫苗前后，对母亲 HIV Env 特异性血浆结合和中和抗体反应进行了表征）参与者。采用单基因组扩增（SGA）获得自体母体病毒的 HIV env基因序列，用于 HIV 感染的怀孕疫苗接种者接种前后血浆中的假病毒产生和中和敏感性测试（ n = 6 gp120， n = 1 gp160）和安慰剂接受者（ n = 3）。我们检测到，在第一次免疫就诊和最后一次分娩就诊期间，疫苗接种者组中 Env 亚基 MN gp120 特异性 IgG 结合有所增加（ P = 0.027，2 边 Wilcoxon 检验）。 虽然各组之间的自体病毒中和效力水平没有观察到差异，但在两组中，分娩时收集的母体血浆比妊娠晚期更能有效地中和妊娠早期的自体病毒。能够进一步增强孕妇体内这些自体病毒 NAB 反应的免疫策略对于阻止 HIV 垂直传播非常重要。