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Paper of The Month Jun 2014

Early development of broadly neutralizing antibodies in HIV-1–infected infants

Nature Medicine 20:655–658.

Authors

1 1] Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Graduate Program in Pathobiology, Department of Global Health, University of Washington, Seattle, Washington, USA.

2 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

3 Department of Pediatrics, University of Nairobi, Nairobi, Kenya.

4 1] Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Abstract

Eliciting protective neutralizing antibodies (NAbs) against HIV-1 is daunting because of the extensive genetic and antigenic diversity of HIV-1. Moreover, broad and potent responses are uncommon even during persistent infection, with only a subset of adults developing broadly neutralizing antibodies (bNAbs) that recognize viral variants from different HIV-1 clades. It is not known whether bNAbs can also arise in HIV-1-infected infants, who typically progress to disease faster than adults, presumably in part due to an immature immune system. Here, we show that bNAbs develop at least as commonly in infants as in adults. Cross-clade NAb responses were detected in 20/28 infected infants, in some cases within 1 year of infection. Among infants with breadth of responses within the top quartile, neutralization of tier 2 or 3 variants from multiple clades was detected at 20 months after infection. These findings suggest that, even in early life, there is sufficient B cell functionality to mount bNAbs against HIV-1. Additionally, the relatively early appearance of bNAbs in infants may provide a unique setting for understanding the pathways of B cell maturation leading to bNAbs.