KEMRI Wellcome Trust Research Programme, Kilifi, Kenya.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
AIDS. 2021 Oct 1;35(12):1895-1905. doi: 10.1097/QAD.0000000000002976.
Antibody function has been extensively studied in HIV-infected adults but is relatively understudied in children. Emerging data suggests enhanced development of broadly neutralizing antibodies (bNAbs) in children but Fc effector functions in this group are less well defined. Here, we profiled overall antibody function in HIV-infected children.
Plasma samples from a cross-sectional study of 50 antiretroviral therapy-naive children (aged 1-11 years) vertically infected with HIV-1 clade A were screened for HIV-specific binding antibody levels and neutralizing and Fc-mediated functions.
Neutralization breadth was determined against a globally representative panel of 12 viruses. HIV-specific antibody levels were determined using a multiplex assay. Fc-mediated antibody functions measured were antibody-dependent: cellular phagocytosis (ADCP); neutrophil phagocytosis (ADNP); complement deposition (ADCD) and natural killer function (ADNK).
All children had HIV gp120-specific antibodies, largely of the IgG1 subtype. Fifty-four percent of the children exhibited more than 50% neutralization breadth, with older children showing significantly broader neutralization activity. Apart from ADCC, observed only in 16% children, other Fc-mediated functions were common (>58% children). Neutralization breadth correlated with Fc-mediated functions suggesting shared determinants of enhanced antibody function exist.
These results are consistent with previous observations that children may develop high levels of neutralization breadth. Furthermore, the striking association between neutralization breadth and Fc effector function suggests that HIV vaccination in children could yield multifunctional antibodies. Paediatric populations may therefore provide an ideal window of opportunity for HIV vaccination strategies.
抗体功能已在感染 HIV 的成年人中得到广泛研究，但在儿童中相对研究较少。新出现的数据表明，儿童体内广泛中和抗体（bNAbs）的发展增强，但该人群中的 Fc 效应功能定义较少。在这里，我们分析了感染 HIV 的儿童的整体抗体功能。
对 50 名未经抗逆转录病毒治疗的（年龄 1-11 岁）垂直感染 HIV-1 组 A 的儿童的横断面研究中的血浆样本进行筛选，以检测 HIV 特异性结合抗体水平以及中和和 Fc 介导的功能。
使用具有代表性的 12 种病毒的全球代表面板确定中和广度。使用多重测定法测定 HIV 特异性抗体水平。测量的 Fc 介导的抗体功能是抗体依赖性：细胞吞噬作用（ADCP）；中性粒细胞吞噬作用（ADNP）；补体沉积（ADCD）和自然杀伤功能（ADNK）。
所有儿童均具有 HIV gp120 特异性抗体，主要为 IgG1 亚型。54%的儿童表现出超过 50%的中和广度，年龄较大的儿童表现出明显更广泛的中和活性。除了仅在 16%的儿童中观察到的 ADCC 外，其他 Fc 介导的功能很常见（>58%的儿童）。中和广度与 Fc 介导的功能相关，表明增强抗体功能存在共同决定因素。
这些结果与先前的观察结果一致，即儿童可能产生高水平的中和广度。此外，中和广度与 Fc 效应功能之间的惊人关联表明，在儿童中进行 HIV 疫苗接种可能会产生多功能抗体。因此，儿科人群可能为 HIV 疫苗接种策略提供了理想的机会窗口。
