Comparison of whole gene and whole virus scrambled antigen approaches for DNA prime and fowlpox virus boost HIV type 1 vaccine regimens in macaques.
T cell immunity plays a critical role in controlling HIV-1 viremia, and encoding a limited set of HIV-1 genes within DNA and poxvirus vectors can, when used sequentially, induce high levels of T cell immunity in primates. However, a limited breadth of T cell immunity exposes the host to potential infection with either genetically diverse HIV-1 strains or T cell escape variants of HIV-1. In an attempt to induce maximally broad immunity, we examined DNA and recombinant fowlpox virus (rFPV) vaccines encoding all HIV-1 genes derived from a global HIV-1 consensus sequence, but expressed as multiple overlapping scrambled 30-amino acid segments (scrambled antigen vaccines, or SAVINEs). Three groups of seven pigtail macaques were immunized with sets of DNA and rFPV expressing Gag/Pol antigens only, the whole genome SAVINE antigens, or no HIV-1 antigens and T cell immunity was monitored by ELISpot and intracellular cytokine staining. High levels of cross-subtype HIV-specific T cell immunity to Gag were consistently induced in the seven macaques primed with DNA and rFPV vaccines expressing Gag/Pol as intact proteins. It was, however, difficult to repeatedly boost immunity with further rFPV immunizations, presumably reflecting high levels of anti- FPV immunity. Unfortunately, this vaccine study did not consistently achieve a broadened level of T cell immunity to multiple HIV genes utilizing the novel whole-virus SAVINE approach, with only one of seven immunized animals generating broad T cell immunity to multiple HIV-1 proteins. Further refinements are planned with alternative vector strategies to evaluate the potential of the SAVINE technology.
Pamungkas
Joko
J
Primate Research Center, Bogor Agricultural University, PSSP-IPB, Bogor, Indonesia 16151.
De Rose
Robert
R
Iskandriati
Diah
D
Noviana
Rachmitasari
R
Paramastri
Yasmina
Y
Dale
C Jane
CJ
Shoobridge
Maryanne
M
Medveczky
C Jill
CJ
Ramshaw
Ian A
IA
Thomson
Scott
S
Kent
Stephen J
SJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D016384:Consensus Sequence; D003429:Cross Reactions; D005587:Fowlpox virus / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D008254:Macaca nemestrina; D023421:Models, Animal; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015488:HIV Antigens; D016655:HIV Core Protein p24; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma