Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual

Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual

Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralizat...

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Main Authors: Khan, Lubina, Makhdoomi, Muzamil Ashraf, Kumar, Sanjeev, Nair, Ambili, Andrabi, Raiees, Clark, Brenda E., Auyeung, Kate, Bhattacharya, Jayanta, Vajpayee, Madhu, Wig, Naveet, Pantophlet, Ralph, Luthra, Kalpana
Format: Online
Language:English
Published: Public Library of Science 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427266/
id pubmed-4427266
recordtype oai_dc
spelling pubmed-44272662015-05-21 Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual Khan, Lubina Makhdoomi, Muzamil Ashraf Kumar, Sanjeev Nair, Ambili Andrabi, Raiees Clark, Brenda E. Auyeung, Kate Bhattacharya, Jayanta Vajpayee, Madhu Wig, Naveet Pantophlet, Ralph Luthra, Kalpana Research Article Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO) revealed that five (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and only one (AIIMS 660) contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization. Public Library of Science 2015-05-11 /pmc/articles/PMC4427266/ /pubmed/25962059 http://dx.doi.org/10.1371/journal.pone.0125575 Text en © 2015 Khan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Khan, Lubina
Makhdoomi, Muzamil Ashraf
Kumar, Sanjeev
Nair, Ambili
Andrabi, Raiees
Clark, Brenda E.
Auyeung, Kate
Bhattacharya, Jayanta
Vajpayee, Madhu
Wig, Naveet
Pantophlet, Ralph
Luthra, Kalpana
spellingShingle Khan, Lubina
Makhdoomi, Muzamil Ashraf
Kumar, Sanjeev
Nair, Ambili
Andrabi, Raiees
Clark, Brenda E.
Auyeung, Kate
Bhattacharya, Jayanta
Vajpayee, Madhu
Wig, Naveet
Pantophlet, Ralph
Luthra, Kalpana
Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual
author_facet Khan, Lubina
Makhdoomi, Muzamil Ashraf
Kumar, Sanjeev
Nair, Ambili
Andrabi, Raiees
Clark, Brenda E.
Auyeung, Kate
Bhattacharya, Jayanta
Vajpayee, Madhu
Wig, Naveet
Pantophlet, Ralph
Luthra, Kalpana
author_sort Khan, Lubina
title Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual
title_short Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual
title_full Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual
title_fullStr Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual
title_full_unstemmed Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual
title_sort identification of cd4-binding site dependent plasma neutralizing antibodies in an hiv-1 infected indian individual
description Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO) revealed that five (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and only one (AIIMS 660) contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization.
publisher Public Library of Science
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427266/
_version_ 1613221823877480448

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