Duke Human Vaccine Institute, Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Immunol Rev. 2017 Jan;275(1):5-10. doi: 10.1111/imr.12517.
Despite major advances in our understanding of the biology of HIV-1 infection, and advances in antiretroviral therapy to treat the disease, there were 2.1 million new cases of HIV-1 infection in 2015, and 36.7 million people living with AIDS (http://www.unaids.org/en/resources/fact-sheet). Thus, a vaccine that can prevent HIV-infection remains a global priority. Thirty-three years after the discovery of HIV-1(1), and the demonstration it was the cause of AIDS(2) and after 6 HIV-1 vaccine efficacy trials (–8), no HIV-1 candidate vaccine has shown enough efficacy to be approved for clinical use. Of several vaccine concepts tested in efficacy trials, only one, the RV144 pox virus prime, protein boost (ALVAC/AIDSVAX B/E) vaccine, showed a low level of vaccine protection with an estimated 31% vaccine efficacy (8). Candidate vaccines have sought to elicit both antibody and T-cell responses, but to fully prevent the acquisition of infection, a major focus has been on the induction of protective antibody responses (9, 10). Hence, the focus of this issue of is “Antibodies and Immunity to HIV”. Animal models have demonstrated that passive administration of HIV-1-- neutralizing antibodies can fully protect against infection, but the induction of such antibodies via immunization remains a major scientific challenge. With recent advances in the isolation and characterization of broadly neutralizing antibodies (bnAbs) from HIV-1-infected subjects, in elucidating structures of the HIV-1 envelope glycoprotein (Env), in defining novel approaches to immunogen design, and in improved understanding of the immunological pathways leading to bNAb elicitation, the challenge developing an HIV-1 vaccine appears to be more tractable. The articles in this issue highlight both major areas of HIV-1 vaccine development progress and remaining obstacles, and provide context for the renewed optimism that a highly effective vaccine, while not imminent, is possible.
尽管我们对 HIV-1 感染的生物学有了重大的认识进展,也有了抗逆转录病毒疗法来治疗这种疾病,但 2015 年仍有 210 万例新的 HIV-1 感染病例,有 3670 万人患有艾滋病(http://www.unaids.org/en/resources/fact-sheet)。因此,预防 HIV 感染的疫苗仍然是全球的重点。在发现 HIV-1 33 年之后(1),并证明它是艾滋病的病因(2),以及在进行了 6 次 HIV-1 疫苗功效试验(–8)之后,没有一种 HIV-1 候选疫苗显示出足够的功效被批准用于临床使用。在功效试验中测试了几种疫苗概念,只有一种疫苗,即 RV144 痘病毒初免-蛋白加强(ALVAC/AIDSVAX B/E)疫苗,显示出低水平的疫苗保护效果,估计疫苗有效率为 31%(8)。候选疫苗试图引发抗体和 T 细胞反应,但为了充分防止感染,主要重点是诱导保护性抗体反应(9,10)。因此,本期的重点是“HIV 的抗体和免疫”。动物模型表明,被动给予 HIV-1 中和抗体可以完全预防感染,但通过免疫接种诱导这种抗体仍然是一个主要的科学挑战。随着最近从 HIV-1 感染的受者中分离和鉴定出广泛中和抗体(bnAbs)的进展,阐明 HIV-1 包膜糖蛋白(Env)的结构,定义新的免疫原设计方法,以及对导致 bnAb 产生的免疫途径的理解的提高,开发 HIV-1 疫苗的挑战似乎更加可行。本期的文章突出了 HIV-1 疫苗开发进展的两个主要领域和仍然存在的障碍,并为重新乐观地认为一种高效疫苗虽然不是迫在眉睫,但有可能实现提供了背景。
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