Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques

Viraj Kulkarni, Antonio Valentin, Margherita Rosati, Candido Alicea, Ashish K. Singh, Rashmi Jalah, Kate E. Broderick, Niranjan Y. Sardesai, Sylvie Le Gall, Beatriz Mothe, Christian Brander, Morgane Rolland, James I. Mullins, George N. Pavlakis, Barbara K. Felber

Research output: Contribution to journalArticleResearchpeer-review

39 Citations (Scopus)

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 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.
Original languageEnglish
Article numbere86254
JournalPLoS ONE
Volume9
Issue number1
DOIs
Publication statusPublished - 23 Jan 2014

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