Format

Send to

Choose Destination
PLoS One. 2014 Jan 23;9(1):e86254. doi: 10.1371/journal.pone.0086254. eCollection 2014.

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

Author information

1
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
2
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
3
Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America.
4
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
5
IrsiCaixa AIDS Research Institute-HIVACAT, Autonomous University of Barcelona, Barcelona, Spain.
6
IrsiCaixa AIDS Research Institute-HIVACAT, Autonomous University of Barcelona, Barcelona, Spain ; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain.
7
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
8
Department of Microbiology, University of Washington, Seattle, Washington, United States of America ; Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.

Erratum in

  • PLoS One. 2014;9(7):e103198.

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.

PMID:
24465991
PMCID:
PMC3900501
DOI:
10.1371/journal.pone.0086254
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center