日期：2015-07-16 期刊：Science Translational Medicine
DOI：10.1126/scitranslmed.aab4005 作者：Heather A. Prentice
一種在幾年前於臨床試驗中被證明有希望的HIV疫苗產生了兩種奇怪的相互矛盾的反應，其中一種反應能保護某些患者免於HIV感染，但另外一種反應則會在其他一些人中增加感染的風險。研究人員現在發現，該疫苗只能為人類白細胞抗原(HLA)基因中有某種特殊變異的人提供免疫保護，該基因可調控抗體的產生。這些結果提示，在後續的研究中(包括目前計劃在南非和泰國進行的臨床試驗)，基因篩檢或能幫助確認那些最能得益於該HIV疫苗的病人亞組。RV144臨床試驗於2009年在泰國完成，它第一次證明一種針對HIV-1感染的疫苗具有部分功效(約31%)。然而，隨後的研究揭示，儘管注射該疫苗可以保護某些病人，但它卻令其他人更容易感染HIV。為了解開這一差異之謎，Heather Prentice和同事對760位試驗參與者的HLA基因型進行了分析。他們發現，帶有一種HLA基因變異株(稱作DPB1*13)的病人會產生一種保護性抗體反應。對這些病人來說，該疫苗的功效估計可激增至71%。但帶有另外一種基因變異株(DQB1*06)的人則情況會變得更糟，這一發現讓人們尤其擔心即將在南非進行的試驗，因為在當地的一般人群中，該HLA變異株要比在泰國更常見。這些結果或可幫助指導疫苗研發並通過選擇具有保護性HLA變異株的患者來設計未來的試驗，因為這些病人會最大程度地受益於該HIV疫苗。
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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.
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