Subtype AE HIV-1 DNA and recombinant Fowlpoxvirus vaccines encoding five shared HIV-1 genes: safety and T cell immunogenicity in macaques.
To induce broad T cell immunity to HIV-1, we evaluated the safety, immunogenicity and dose-response relationship of DNA and recombinant Fowlpoxvirus (rFPV) vaccines encoding five shared HIV subtype AE genes (Gag, Pol, Env, Tat, Rev) in pigtail macaques. The DNA (three doses of either 1 mg or 4.5 mg) and rFPV (a single boost of either 5 x 10(7) or 2 x 10(8) plaque forming units) vaccines were administered intramuscularly without adjuvants. Broadly reactive HIV-specific T cell immunity was stimulated by all doses of the vaccines administered, without significant differences between the high and low doses studied. The vaccines induced both CD4 and CD8 T cell responses to Gag, Pol, Env and Tat/Rev proteins, with CD4 T cell responses being greater in magnitude than CD8 T cell responses. The vaccine-induced T cell responses had significant cross-recognition of heterologous HIV-1 proteins from non-AE HIV-1 subtypes. In conclusion, these subtype AE HIV-1 DNA and rFPV vaccines were safe, induced broad T-cell immunity in macaques, and are suitable for progression into clinical trials.
De Rose
Robert
R
Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Vic. 3010, Australia.
Chea
Socheata
S
Dale
C Jane
CJ
Reece
Jeanette
J
Fernandez
Caroline S
CS
Wilson
Kim M
KM
Thomson
Scott
S
Ramshaw
Ian A
IA
Coupar
Barbara E H
BE
Boyle
David B
DB
Sullivan
Mark T
MT
Kent
Stephen J
SJ
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005587:Fowlpox virus / Q000276:immunology*; D005814:Genes, Viral / Q000235:genetics; D015483:HIV Antibodies / Q000032:analysis / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008254:Macaca nemestrina; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D016915:AIDS Vaccines; D016207:Cytokines; D004279:DNA, Viral; D015483:HIV Antibodies; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma