Kulkarni V, Valentin A, Rosati M, Alicea C, Singh AK, Jalah R, Broderick KE, Sardesai NY, Le Gall S, Mothe B, Brander C, Rolland M, Mullins JI, Pavlakis GN, Felber BK (2014). Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques. PloS one, 9(1), e86254. (pubmed) (doi)
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.