Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies.

Published

Journal Article (Review)

Induction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV-1) is a key, as-yet-unachieved goal of prophylactic HIV-1 vaccine strategies. However, some HIV-infected individuals develop bnAbs after approximately 2-4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy-chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV-1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV-1 vaccine design.

Full Text

Duke Authors

Cited Authors

  • Borrow, P; Moody, MA

Published Date

  • January 2017

Published In

Volume / Issue

  • 275 / 1

Start / End Page

  • 62 - 78

PubMed ID

  • 28133804

Pubmed Central ID

  • 28133804

Electronic International Standard Serial Number (EISSN)

  • 1600-065X

International Standard Serial Number (ISSN)

  • 0105-2896

Digital Object Identifier (DOI)

  • 10.1111/imr.12504

Language

  • eng