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Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

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 approximatel...

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Autores principales: Borrow, Persephone, Moody, M. Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299500/
https://www.ncbi.nlm.nih.gov/pubmed/28133804
http://dx.doi.org/10.1111/imr.12504
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author Borrow, Persephone
Moody, M. Anthony
author_facet Borrow, Persephone
Moody, M. Anthony
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description 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.
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spelling pubmed-52995002017-02-22 Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies Borrow, Persephone Moody, M. Anthony Immunol Rev Invited Reviews 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. John Wiley and Sons Inc. 2017-01-30 2017-01 /pmc/articles/PMC5299500/ /pubmed/28133804 http://dx.doi.org/10.1111/imr.12504 Text en © 2017 The Authors. Immunological Reviews published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Reviews
Borrow, Persephone
Moody, M. Anthony
Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies
title Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies
title_full Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies
title_fullStr Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies
title_full_unstemmed Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies
title_short Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies
title_sort immunologic characteristics of hiv‐infected individuals who make broadly neutralizing antibodies
topic Invited Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299500/
https://www.ncbi.nlm.nih.gov/pubmed/28133804
http://dx.doi.org/10.1111/imr.12504
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