Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques.
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.
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
Viraj
V
Kulkarni
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
Antonio
A
Valentin
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
Margherita
M
Rosati
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
Candido
C
Alicea
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
Ashish K
AK
Singh
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
Rashmi
R
Jalah
Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America.
Kate E
KE
Broderick
Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America.
Niranjan Y
NY
Sardesai
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Sylvie
S
Le Gall
IrsiCaixa AIDS Research Institute-HIVACAT, Autonomous University of Barcelona, Barcelona, Spain.
Beatriz
B
Mothe
IrsiCaixa AIDS Research Institute-HIVACAT, Autonomous University of Barcelona, Barcelona, Spain ; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain.
Christian
C
Brander
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
Morgane
M
Rolland
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.
James I
JI
Mullins
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
George N
GN
Pavlakis
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
Barbara K
BK
Felber
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D017124:Conserved Sequence; D004279:DNA, Viral / Q000235:genetics; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008253:Macaca mulatta; D011498:Protein Precursors / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D016915:AIDS Vaccines; D004279:DNA, Viral; D011498:Protein Precursors; D019444:Vaccines, DNA; C059767:p55 gag precursor protein, Human immunodeficiency virus 1