The immune response during acute HIV-1 infection: clues for vaccine development.
The immune response during acute HIV-1 infection: clues for vaccine development.
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DOI：
10.1038/nri2674
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发表时间：
2010-01
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HIV-1 感染的早期病毒学因素，包括传播方式和病毒的性质，可以影响病毒血症从早期高峰到设定点的时间进程。 HIV-1感染最初几周内对患者的识别提供了免疫系统损伤的早期证据，包括CD4+ T细胞的大量凋亡（这与血液中凋亡微粒和TRAIL（肿瘤坏死因子相关凋亡诱导配体）的存在有关）以及粘膜淋巴组织中生发中心的损伤。最初的先天免疫反应包括急性期蛋白的出现、早期细胞因子风暴和自然杀伤 (NK) 细胞的激活。然而，针对 HIV-1 的先天免疫反应可能具有破坏性，因为它会将易感 T 细胞吸引到感染灶。第一个 T 细胞反应通过杀死受感染的 T 细胞来控制创始人病毒。然而，T 细胞反应也会选择创始人病毒的突变变化，从而允许免疫逃避。第一个 B 细胞反应由早期免疫复合物组成，随后是针对创始病毒的非中和抗体，然后是广泛作用的中和抗体的缓慢发展。开发快速诱导广泛作用的中和抗体的疫苗可能有助于预防艾滋病毒感染。了解早期事件和免疫反应对于制定疫苗策略至关重要，这些策略可以改善当前正在试验的 HIV 疫苗（例如 RV144（泰国）功效试验）所提供的薄弱保护。对 HIV-1 感染早期阶段的前所未有的了解为疫苗设计提供了重要线索。在这里，作者讨论了早期病毒学和免疫学事件（包括单一创始人病毒的传播和明显的 CD4+T 细胞损失）如何影响疾病进程。 HIV-1感染的早期免疫反应可能是决定临床病程的重要因素。最近的数据表明，粘膜感染后出现的 HIV-1 准种通常源自单一传播病毒。此外，第一个有效的免疫反应驱动了病毒逃逸突变的选择，这一发现提供了对针对传播病毒的最早的免疫反应及其对控制急性病毒血症的贡献的深入了解。随后发生强烈的先天性和适应性免疫反应，但为时已晚，无法消除感染。在这篇综述中，我们讨论了最近关于 HIV-1 早期免疫反应的动力学和质量的研究及其对开发成功的预防性 HIV-1 疫苗的影响。
The early virological factors in HIV-1 infection, including transmission and the nature of the founder virus, can affect the time course of viraemia through the early peak to set point. The identification of patients within the first few weeks of HIV-1 infection has provided early evidence of immune system damage, including massive apoptosis of CD4+ T cells, which is associated with the presence of apoptotic microparticles and TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) in the blood, and damage to germinal centres in mucosal lymphoid tissues. The first innate immune responses include the appearance of acute-phase proteins, early cytokine storm and activation of natural killer (NK) cells. An innate immune response to HIV-1 can be damaging, however, as it can draw susceptible T cells to the infection foci. The first T cell response controls the founder virus by killing infected T cells. However, the T cell response also selects mutational changes in the founder virus, allowing immune evasion. The first B cell response consists of early immune complexes, followed by non-neutralizing antibodies against the founder virus and then the slow development of broadly acting neutralizing antibodies. Development of vaccines that rapidly induce broadly acting neutralizing antibodies might be beneficial in preventing HIV infection. Understanding the early events and immune responses is crucial to devising vaccine strategies that can improve the weak protection offered by current HIV vaccines that are being trialled, such as the RV144 (Thai) efficacy trial. Unprecedented insight into the early stages of HIV-1 infection has provided important clues for vaccine design. Here, the authors discuss how early virological and immunological events, including transmission by a single founder virus and marked CD4+T cell loss, might influence the course of disease. The early immune response to HIV-1 infection is likely to be an important factor in determining the clinical course of disease. Recent data indicate that the HIV-1 quasispecies that arise following a mucosal infection are usually derived from a single transmitted virus. Moreover, the finding that the first effective immune responses drive the selection of virus escape mutations provides insight into the earliest immune responses against the transmitted virus and their contributions to the control of acute viraemia. Strong innate and adaptive immune responses occur subsequently but they are too late to eliminate the infection. In this Review, we discuss recent studies on the kinetics and quality of early immune responses to HIV-1 and their implications for developing a successful preventive HIV-1 vaccine.
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