Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques
Kulkarni, Viraj (National Cancer Institute, Frederick, Maryland, United States of America)
Valentin, Antonio (National Cancer Institute, Frederick, Maryland, United States of America)
Rosati, Margherita (National Cancer Institute, Frederick, Maryland, United States of America)
Alicea, Cándido (National Cancer Institute, Frederick, Maryland, United States of America)
Singh, Ashish K. (National Cancer Institute, Frederick, Maryland, United States of America)
Jalah, Rashmi (National Cancer Institute, Frederick, Maryland, United States of America)
Broderick, Kate E. (Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America)
Sardesai, Niranjan Y. (Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America)
Le Gall, Sylvie (Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America)
Mothe, Beatriz (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Rolland, Morgane (University of Washington, Seattle, Washington, United States of America)
Mullins, James I. (University of Washington, Seattle, Washington, United States of America)
Pavlakis, George N. (National Cancer Institute, Frederick, Maryland, United States of America)
Felber, Barbara K. (National Cancer Institute, Frederick, Maryland, United States of America)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2014
Abstract:	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 p24 gag 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 p55 gag 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 9 (january 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0086254
PMID: 24465991

13 p, 1.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
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