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CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques

Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T follicular helper (Tfh) responses. Using the VC10014...

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Autores principales: Sarkar, Sanghita, Spencer, David A., Barnette, Philip, Pandey, Shilpi, Sutton, William F., Basu, Madhubanti, Burch, Reuben E., Cleveland, John D., Rosenberg, Alexander F., Rangel-Moreno, Javier, Keefer, Michael C., Hessell, Ann J., Haigwood, Nancy L., Kobie, James J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564110/
https://www.ncbi.nlm.nih.gov/pubmed/34745131
http://dx.doi.org/10.3389/fimmu.2021.757811
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author Sarkar, Sanghita
Spencer, David A.
Barnette, Philip
Pandey, Shilpi
Sutton, William F.
Basu, Madhubanti
Burch, Reuben E.
Cleveland, John D.
Rosenberg, Alexander F.
Rangel-Moreno, Javier
Keefer, Michael C.
Hessell, Ann J.
Haigwood, Nancy L.
Kobie, James J.
author_facet Sarkar, Sanghita
Spencer, David A.
Barnette, Philip
Pandey, Shilpi
Sutton, William F.
Basu, Madhubanti
Burch, Reuben E.
Cleveland, John D.
Rosenberg, Alexander F.
Rangel-Moreno, Javier
Keefer, Michael C.
Hessell, Ann J.
Haigwood, Nancy L.
Kobie, James J.
author_sort Sarkar, Sanghita
collection PubMed
description Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T follicular helper (Tfh) responses. Using the VC10014 DNA-protein co-immunization vaccine platform consisting of gp160 plasmids and gp140 trimeric proteins derived from an HIV-1 infected subject that developed bNAbs, we determined the characteristics of the Env-specific humoral response in vaccinated rhesus macaques in the context of CD4+ T cell depletion. Unexpectedly, both CD4+ depleted and non-depleted animals developed comparable Tier 1 and 2 heterologous HIV-1 neutralizing plasma antibody titers. There was no deficit in protection from SHIV challenge, no diminution of titers of HIV Env-specific cross-clade binding antibodies, antibody dependent cellular phagocytosis, or antibody-dependent complement deposition in the CD4+ depleted animals. These collective results suggest that in the presence of diminished CD4+ T cell help, HIV neutralizing antibodies were still generated, which may have implications for developing effective HIV vaccine strategies.
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spelling pubmed-85641102021-11-04 CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques Sarkar, Sanghita Spencer, David A. Barnette, Philip Pandey, Shilpi Sutton, William F. Basu, Madhubanti Burch, Reuben E. Cleveland, John D. Rosenberg, Alexander F. Rangel-Moreno, Javier Keefer, Michael C. Hessell, Ann J. Haigwood, Nancy L. Kobie, James J. Front Immunol Immunology Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T follicular helper (Tfh) responses. Using the VC10014 DNA-protein co-immunization vaccine platform consisting of gp160 plasmids and gp140 trimeric proteins derived from an HIV-1 infected subject that developed bNAbs, we determined the characteristics of the Env-specific humoral response in vaccinated rhesus macaques in the context of CD4+ T cell depletion. Unexpectedly, both CD4+ depleted and non-depleted animals developed comparable Tier 1 and 2 heterologous HIV-1 neutralizing plasma antibody titers. There was no deficit in protection from SHIV challenge, no diminution of titers of HIV Env-specific cross-clade binding antibodies, antibody dependent cellular phagocytosis, or antibody-dependent complement deposition in the CD4+ depleted animals. These collective results suggest that in the presence of diminished CD4+ T cell help, HIV neutralizing antibodies were still generated, which may have implications for developing effective HIV vaccine strategies. Frontiers Media S.A. 2021-10-20 /pmc/articles/PMC8564110/ /pubmed/34745131 http://dx.doi.org/10.3389/fimmu.2021.757811 Text en Copyright © 2021 Sarkar, Spencer, Barnette, Pandey, Sutton, Basu, Burch, Cleveland, Rosenberg, Rangel-Moreno, Keefer, Hessell, Haigwood and Kobie https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Sarkar, Sanghita
Spencer, David A.
Barnette, Philip
Pandey, Shilpi
Sutton, William F.
Basu, Madhubanti
Burch, Reuben E.
Cleveland, John D.
Rosenberg, Alexander F.
Rangel-Moreno, Javier
Keefer, Michael C.
Hessell, Ann J.
Haigwood, Nancy L.
Kobie, James J.
CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques
title CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques
title_full CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques
title_fullStr CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques
title_full_unstemmed CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques
title_short CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques
title_sort cd4+ t cells are dispensable for induction of broad heterologous hiv neutralizing antibodies in rhesus macaques
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564110/
https://www.ncbi.nlm.nih.gov/pubmed/34745131
http://dx.doi.org/10.3389/fimmu.2021.757811
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