一种在几年前于临床试验中被证明有希望的HIV疫苗产生了两种奇怪的相互矛盾的反应，其中一种反应能保护某些患者免于HIV感染，但另外一种反应则会在其他一些人中增加感染的风险。研究人员现在发现，该疫苗只能为人类白细胞抗原(HLA)基因中有某种特殊变异的人提供免疫保护，该基因可调控抗体的产生。这些结果提示，在后续的研究中(包括目前计划在南非和泰国进行的临床试验)，基因筛检或能帮助确认那些最能得益于该HIV疫苗的病人亚组。RV144临床试验于2009年在泰国完成，它第一次证明一种针对HIV-1感染的疫苗具有部分功效(约31%)。然而，随后的研究揭示，尽管注射该疫苗可以保护某些病人，但它却令其他人更容易感染HIV。为了解开这一差异之谜，Heather Prentice和同事对760位试验参与者的HLA基因型进行了分析。他们发现，带有一种HLA基因变异株(称作DPB1*13)的病人会产生一种保护性抗体反应。对这些病人来说，该疫苗的功效估计可激增至71%。但带有另外一种基因变异株(DQB1*06)的人则情况会变得更糟，这一发现让人们尤其担心即将在南非进行的试验，因为在当地的一般人群中，该HLA变异株要比在泰国更常见。这些结果或可帮助指导疫苗研发并通过选择具有保护性HLA变异株的患者来设计未来的试验，因为这些病人会最大程度地受益于该HIV疫苗。

    原文链接：HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition

    原文摘要：In the RV144 vaccine trial, two antibody responses were found to correlate with HIV-1 acquisition. Because human leukocyte antigen (HLA) class II–restricted CD4+ T cells are involved in antibody production, we tested whether HLA class II genotypes affected HIV-1–specific antibody levels and HIV-1 acquisition in 760 individuals. Indeed, antibody responses correlated with acquisition only in the presence of single host HLA alleles. Envelope (Env)–specific immunoglobulin A (IgA) antibodies were associated with increased risk of acquisition specifically in individuals with DQB1*06. IgG antibody responses to Env amino acid positions 120 to 204 were higher and were associated with decreased risk of acquisition and increased vaccine efficacy only in the presence of DPB1*13. Screening IgG responses to overlapping peptides spanning Env 120–204 and viral sequence analysis of infected individuals defined differences in vaccine response that were associated with the presence of DPB1*13 and could be responsible for the protection observed. Overall, the underlying genetic findings indicate that HLA class II modulated the quantity, quality, and efficacy of antibody responses in the RV144 trial.