宿主的遗传特性或在HIV疫苗的效率发挥上扮演着重要角色

  近日，一项发表自国际杂志Science Translational Medicine上的研究论文中，研究者发现，在泰国进行的RV144 HIV疫苗试验中，宿主的遗传特性或在帮助机体抵御HIV感染的效力上扮演着重要作用；日前来自美国军方HIV研究组的科学家们检测了名为HLA的免疫反应基因的特殊突变是否和机体抵御HIV感染的保护能力相关。
  研究者Rasmi Thomas表示，我们发现，和增加或降低HIV感染风险相关的抗体反应仅在宿主特殊的HLA等位基因存在时才会出现，而通过鉴别特殊的等位基因或基因突变，或可帮助科学家们确定机体被保护的分子机制。目前进行的RV144试验仅是HIV疫苗的试验，用以阐明个体在过去42个月的研究过程中该疫苗保护机体抵御HIV-1感染的作用效率，而研究者对比了受保护个体未未受保护个体的研究数据，随后进行了RV144试验则可帮助理解HIV疫苗诱导的机体保护性免疫反应。
  此前研究者鉴别出了两种和HIV感染风险相关的免疫，而接下来的研究中他们又分析了病毒和宿主机体的遗传特性来更好地揭示疫苗的工作机理；HLA 2类分子在机体抗体反应的表现上发挥着重要作用，因此研究者在RV144疫苗试验中检测了基因的突变体同疫苗作用效率之间的相互作用关系；研究结果表明，特殊的HLA 2类分子可以调节疫苗诱导的抗体反应的质量和程度，从而来影响个体的HIV感染率及疫苗的作用效力。
  最后研究者说道，本文研究确定了宿主的遗传特性对于HIV疫苗保护机体功效的重要性，其也会后期进行新一代HIV疫苗的开发提供新的研究线索和思路。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition
Science Translational Medicine    DOI: 10.1126/scitranslmed.aab4005
H. A. Prentice, G. D. Tomaras, D. E. Geraghty, R. Apps, Y. Fong, P. K. Ehrenberg, M. Rolland, G. H. Kijak, S. J. Krebs, W. Nelson, A. DeCamp, X. Shen, N. L. Yates, S. Zolla-Pazner, S. Nitayaphan, S. Rerks-Ngarm, J. Kaewkungwal, P. Pitisuttithum, G. Ferrari, M. J. McElrath, D. C. Montefiori, R. T. Bailer, R. A. Koup, R. J. O'Connell, M. L. Robb, N. L. Michael, P. B. Gilbert, J. H. Kim, R. Thomas. 
An HIV vaccine that proved promising several years ago in clinical trials produced two oddly conflicting responses, one protecting some patients from HIV infection and another raising the risk of infection in others. Researchers now find that the vaccine afforded immune protection only to individuals with a specific variant in their human leukocyte antigen (HLA) gene, which regulates antibody production. The results suggest that in follow-up studies, including clinical trials currently planned in South Africa and Thailand, genetic screening may help identify the subset of patients who would benefit most from the HIV vaccine. The RV144 clinical trial, completed in Thailand in 2009, was the first to demonstrate partial efficacy of a vaccine (about 31%) against HIV-1 infection. However, subsequent studies revealed that while the shot protected some patients, it made others more susceptible to the virus. To solve this discrepancy, Heather Prentice and colleagues analyzed the HLA genotypes of 760 trial participants. They found that patients with an HLA gene variant called DPB1*13 produced a protective antibody response. For these patients, the vaccine’s efficacy jumped to an estimated 71%. Individuals carrying another variant, DQB1*06, were left worse off, a finding of particular concern for the upcoming trial in South Africa, where this HLA variant is more common in the general population than in Thailand. The results may help guide vaccine development and design of future trials by selecting for patients with the protective HLA variant who would benefit most from the HIV vaccine.

附两篇扩展性研究：

[1] Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand.
[2] Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial.