Program in Immunology and Molecular Pathogenesis, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University.
Department of Pediatrics, Emory University School of Medicine.
Curr Opin HIV AIDS. 2024 Jul 1;19(4):201-211. doi: 10.1097/COH.0000000000000857. Epub 2024 May 2.
Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies.
During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials.
Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.
综述目的：通过了解在未接受抗逆转录病毒治疗（ART）和接受 ART 情况下，儿童感染人类免疫缺陷病毒（HIV）期间 HIV 控制的动力学，了解免疫疗法的机会/潜力，这在感染猴免疫缺陷病毒（SIV）和猴 HIV （SHIV）的恒河猴和临床试验中得到了观察。本综述概述了传播模式、儿童 HIV 的发病机制、婴儿免疫系统的独特方面、婴儿恒河猴模型和免疫疗法。
最近的发现：在围产期 HIV 感染的最早阶段，婴儿免疫系统的特点是一个独特的环境，由免疫耐受和缺乏 HIV 特异性 T 细胞反应定义，这有助于疾病进展。此外，初级淋巴器官，如胸腺，在儿童 HIV 感染者（CLWH）的 HIV 发病机制中似乎发挥着独特的作用。免疫系统的关键组成部分决定了病毒控制的程度、诱导病毒控制的策略的目标以及对免疫疗法的反应。对高效广泛中和抗体（bNAbs）和 T 细胞疫苗的追求彻底改变了 HIV 治愈的方法。HIV-1 特异性 bNAbs 的给药，靶向高度可变的包膜，改善了体液免疫，而 T 细胞疫苗诱导或改善了 HIV-1 特异性 CD8+ T 细胞的细胞毒性反应，这两者都是控制病毒和无 ART 缓解的有前途的选择，正如已完成和正在进行的临床试验所证明的那样。
总结：了解 CLWH 感染期间早期的 HIV 感染和疾病进展事件，为利用免疫系统的自然反应预测或针对后期结果提供了基础。发育中的儿童免疫系统为特定的长期免疫疗法提供了多种机会，这些疗法能够提高青少年和成年期的生活质量。
