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Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies

INTRODUCTION: A primary focus of HIV‐1 vaccine development is the activation of B cell receptors for naïve or precursor broadly neutralizing antibodies (bnAbs), followed by expansion and maturation of bnAb B cell lineage intermediates leading to highly affinity‐matured bnAbs. HIV‐1 envelope (Env) en...

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Autores principales: Williams, Wilton B., Wiehe, Kevin, Saunders, Kevin O., Haynes, Barton F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606870/
https://www.ncbi.nlm.nih.gov/pubmed/34806332
http://dx.doi.org/10.1002/jia2.25831
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author Williams, Wilton B.
Wiehe, Kevin
Saunders, Kevin O.
Haynes, Barton F.
author_facet Williams, Wilton B.
Wiehe, Kevin
Saunders, Kevin O.
Haynes, Barton F.
author_sort Williams, Wilton B.
collection PubMed
description INTRODUCTION: A primary focus of HIV‐1 vaccine development is the activation of B cell receptors for naïve or precursor broadly neutralizing antibodies (bnAbs), followed by expansion and maturation of bnAb B cell lineage intermediates leading to highly affinity‐matured bnAbs. HIV‐1 envelope (Env) encodes epitopes for bnAbs of different specificities. Design of immunogens to induce bnAb precursors of different specificities and mature them into bnAb status is a goal for HIV‐1 vaccine development. We review vaccine strategies for bnAb lineages development and highlight the immunological barriers that these strategies must overcome to generate bnAbs. METHODS: We provide perspectives based on published research articles and reviews. DISCUSSION: The recent Antibody Mediated Protection (AMP) trial that tested the protective efficacy of one HIV‐1 Env bnAb specificity demonstrated that relatively high levels of long‐lasting serum titers of multiple specificities of bnAbs will be required for protection from HIV‐1 transmission. Current vaccine efforts for induction of bnAb lineages are focused on immunogens designed to expand naïve HIV‐1 bnAb precursor B cells following the recent success of vaccine‐induction of bnAb precursor B cells in macaques and humans. BnAb precursor B cells serve as templates for priming‐immunogen design. However, design of boosting immunogens for bnAb maturation requires knowledge of the optimal immunogen design and immunological environment for bnAb B cell lineage affinity maturation. BnAb lineages acquire rare genetic changes as mutations during B cell maturation. Moreover, the immunological environment that supports bnAb development during HIV‐1 infection is perturbed with an altered B cell repertoire and dysfunctional immunoregulatory controls, suggesting that in normal settings, bnAb development will be disfavoured. Thus, strategies for vaccine induction of bnAbs must circumvent immunological barriers for bnAb development that normally constrain bnAb B cell affinity maturation. CONCLUSIONS: A fully protective HIV‐1 vaccine needs to induce durable high titers of bnAbs that can be generated by a sequential set of Env immunogens for expansion and maturation of bnAb B cell lineages in a permitted immunological environment. Moreover, multiple specificities of bnAbs will be required to be sufficiently broad to prevent the escape of HIV‐1 strains during transmission.
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spelling pubmed-86068702021-11-29 Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies Williams, Wilton B. Wiehe, Kevin Saunders, Kevin O. Haynes, Barton F. J Int AIDS Soc Supplement: Reviews INTRODUCTION: A primary focus of HIV‐1 vaccine development is the activation of B cell receptors for naïve or precursor broadly neutralizing antibodies (bnAbs), followed by expansion and maturation of bnAb B cell lineage intermediates leading to highly affinity‐matured bnAbs. HIV‐1 envelope (Env) encodes epitopes for bnAbs of different specificities. Design of immunogens to induce bnAb precursors of different specificities and mature them into bnAb status is a goal for HIV‐1 vaccine development. We review vaccine strategies for bnAb lineages development and highlight the immunological barriers that these strategies must overcome to generate bnAbs. METHODS: We provide perspectives based on published research articles and reviews. DISCUSSION: The recent Antibody Mediated Protection (AMP) trial that tested the protective efficacy of one HIV‐1 Env bnAb specificity demonstrated that relatively high levels of long‐lasting serum titers of multiple specificities of bnAbs will be required for protection from HIV‐1 transmission. Current vaccine efforts for induction of bnAb lineages are focused on immunogens designed to expand naïve HIV‐1 bnAb precursor B cells following the recent success of vaccine‐induction of bnAb precursor B cells in macaques and humans. BnAb precursor B cells serve as templates for priming‐immunogen design. However, design of boosting immunogens for bnAb maturation requires knowledge of the optimal immunogen design and immunological environment for bnAb B cell lineage affinity maturation. BnAb lineages acquire rare genetic changes as mutations during B cell maturation. Moreover, the immunological environment that supports bnAb development during HIV‐1 infection is perturbed with an altered B cell repertoire and dysfunctional immunoregulatory controls, suggesting that in normal settings, bnAb development will be disfavoured. Thus, strategies for vaccine induction of bnAbs must circumvent immunological barriers for bnAb development that normally constrain bnAb B cell affinity maturation. CONCLUSIONS: A fully protective HIV‐1 vaccine needs to induce durable high titers of bnAbs that can be generated by a sequential set of Env immunogens for expansion and maturation of bnAb B cell lineages in a permitted immunological environment. Moreover, multiple specificities of bnAbs will be required to be sufficiently broad to prevent the escape of HIV‐1 strains during transmission. John Wiley and Sons Inc. 2021-11-21 /pmc/articles/PMC8606870/ /pubmed/34806332 http://dx.doi.org/10.1002/jia2.25831 Text en © 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Supplement: Reviews
Williams, Wilton B.
Wiehe, Kevin
Saunders, Kevin O.
Haynes, Barton F.
Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies
title Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies
title_full Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies
title_fullStr Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies
title_full_unstemmed Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies
title_short Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies
title_sort strategies for induction of hiv‐1 envelope‐reactive broadly neutralizing antibodies
topic Supplement: Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606870/
https://www.ncbi.nlm.nih.gov/pubmed/34806332
http://dx.doi.org/10.1002/jia2.25831
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