Duke University Medical Center, Durham, North Carolina, USA.
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
J Infect Dis. 2022 May 16;225(10):1731-1740. doi: 10.1093/infdis/jiab629.
Recent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults.
We evaluated plasma from 212 antiretroviral therapy-naive children with HIV (1-3 years old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity, and immunoglobulin (Ig)G subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay.
One-year-old children demonstrated neutralization breadth comparable to chronically infected adults, whereas 2- and 3-year-olds exhibited significantly greater neutralization breadth (P = .014). Likewise, binding antibody responses increased with age, with levels in 2- and 3-year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. It is interesting to note that the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, which suggests that most children may develop a polyclonal neutralization response.
These results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.
最近的研究表明,与成年人相比,儿童在感染人类免疫缺陷病毒(HIV)后可能更早产生广泛中和抗体(bnAbs)。
我们评估了 212 名抗逆转录病毒治疗初治 HIV 感染儿童(1-3 岁)的血浆。使用包含 10 种病毒的面板评估了中和广度和效力,并与慢性 HIV 感染的成年人进行了比较。使用结合抗体多重分析评估了Env 特异性抗体的大小、表位特异性和 IgG 亚类分布。
1 岁儿童的中和广度与慢性感染的成年人相当,而 2 岁和 3 岁儿童的中和广度显著更大(P=0.014)。同样,结合抗体反应随着年龄的增长而增加,2 岁和 3 岁儿童的水平与成年人相当。总体而言,儿科和成人队列之间在抗体特异性或 IgG 亚类分布方面没有显著差异。有趣的是,只有 5 份 38 份儿科广泛中和样本的中和活性映射到单个表位(CD4 结合位点、V2 或 V3 聚糖),这表明大多数儿童可能会产生多克隆中和反应。
这些结果为越来越多的证据做出了贡献,表明在生命早期启动 HIV 免疫可能为广泛中和抗体反应的发展带来优势。