Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques

HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24gag elements (CE) induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited respons...

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Main Authors:	Kulkarni, Viraj, Valentin, Antonio, Rosati, Margherita, Alicea, Candido, Singh, Ashish K., Jalah, Rashmi, Broderick, Kate E., Sardesai, Niranjan Y., Le Gall, Sylvie, Mothe, Beatriz, Brander, Christian, Rolland, Morgane, Mullins, James I., Pavlakis, George N., Felber, Barbara K.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900501/

id	pubmed-3900501
recordtype	oai_dc
spelling	pubmed-39005012014-01-24 Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques Kulkarni, Viraj Valentin, Antonio Rosati, Margherita Alicea, Candido Singh, Ashish K. Jalah, Rashmi Broderick, Kate E. Sardesai, Niranjan Y. Le Gall, Sylvie Mothe, Beatriz Brander, Christian Rolland, Morgane Mullins, James I. Pavlakis, George N. Felber, Barbara K. Research Article HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24gag elements (CE) induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55gag increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist. Public Library of Science 2014-01-23 /pmc/articles/PMC3900501/ /pubmed/24465991 http://dx.doi.org/10.1371/journal.pone.0086254 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
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	Kulkarni, Viraj Valentin, Antonio Rosati, Margherita Alicea, Candido Singh, Ashish K. Jalah, Rashmi Broderick, Kate E. Sardesai, Niranjan Y. Le Gall, Sylvie Mothe, Beatriz Brander, Christian Rolland, Morgane Mullins, James I. Pavlakis, George N. Felber, Barbara K.
spellingShingle	Kulkarni, Viraj Valentin, Antonio Rosati, Margherita Alicea, Candido Singh, Ashish K. Jalah, Rashmi Broderick, Kate E. Sardesai, Niranjan Y. Le Gall, Sylvie Mothe, Beatriz Brander, Christian Rolland, Morgane Mullins, James I. Pavlakis, George N. Felber, Barbara K. Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques
author_facet	Kulkarni, Viraj Valentin, Antonio Rosati, Margherita Alicea, Candido Singh, Ashish K. Jalah, Rashmi Broderick, Kate E. Sardesai, Niranjan Y. Le Gall, Sylvie Mothe, Beatriz Brander, Christian Rolland, Morgane Mullins, James I. Pavlakis, George N. Felber, Barbara K.
author_sort	Kulkarni, Viraj
title	Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques
title_short	Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques
title_full	Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques
title_fullStr	Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques
title_full_unstemmed	Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques
title_sort	altered response hierarchy and increased t-cell breadth upon hiv-1 conserved element dna vaccination in macaques
description	HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24gag elements (CE) induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55gag increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900501/
_version_	1612050701225033728

Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques

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