Frequent Development of Broadly Neutralizing Antibodies in Early Life in a Large Cohort of Children With Human Immunodeficiency Virus.

Abstract

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.