Evaluation in macaques of HIV-1 DNA vaccines containing primate CpG motifs and fowlpoxvirus vaccines co-expressing IFNgamma or IL-12.
Induction of HIV-specific T-cell responses by vaccines may facilitate efficient control of HIV. Plasmid DNA vaccines and recombinant fowlpoxvirus (rFPV) vaccines are promising HIV-1 vaccine candidates, although either vaccine alone may be insufficient to protect against HIV-1. A consecutive immunisation strategy involving priming with DNA and boosting with rFPV vaccines encoding multiple common HIV-1 antigens was further evaluated in 30 macaques. The DNA vaccine vector included CpG immunostimulatory molecules, and rFPV vaccines were compared with rFPV vaccines co-expressing the pro-T cell cytokines IFNgamma or IL-12. Vaccines expressed multiple HIV-1 genes, mutated to remove active sites of the HIV proteins. The vaccines were well tolerated, and a significant enhancement of DNA-vaccine primed HIV-1 specific T lymphocyte responses was observed following rFPV boosting. Co-expression of IFNgamma or IL-12 by the rFPV vaccines did not further enhance immune responses. Non-sterilising protection from a non-pathogenic HIV-1 challenge was observed. This study provides evidence of a safe, optimised, strategy for the generation of T-cell mediated immunity to HIV-1.
Dale
C Jane
CJ
Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Vic. 3010, Australia.
De Rose
Robert
R
Wilson
Kim M
KM
Croom
Hayley A
HA
Thomson
Scott
S
Coupar
Barbara E H
BE
Ramsay
Alistair
A
Purcell
Damian F J
DF
Ffrench
Rosemary
R
Law
Matthew
M
Emery
Sean
S
Cooper
David A
DA
Ramshaw
Ian A
IA
Boyle
David B
DB
Kent
Stephen J
SJ
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D004279:DNA, Viral / Q000032:analysis; D005069:Evaluation Studies as Topic; D005587:Fowlpox virus / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D018664:Interleukin-12 / Q000235:genetics; D008251:Macaca; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000633:toxicity; D014765:Viral Vaccines / Q000276:immunology / Q000633:toxicity
D016915:AIDS Vaccines; D004279:DNA, Viral; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D018664:Interleukin-12