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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Conserved Sequence
  • DNA, Viral / genetics
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Immunity, Cellular
  • Immunization, Secondary
  • Macaca mulatta
  • Protein Precursors / genetics
  • T-Lymphocytes / immunology*
  • Vaccination*
  • Vaccines, DNA / immunology*


  • AIDS Vaccines
  • DNA, Viral
  • Protein Precursors
  • Vaccines, DNA
  • p55 gag precursor protein, Human immunodeficiency virus 1