title: Evaluation in macaques of HIV-1 DNA vaccines containing primate CpG motifs and fowlpoxvirus vaccines co-expressing IFNgamma or IL-12.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Vic. 3010, Australia.
authors.forename: C Jane
authors.initials: CJ
authors.lastname: Dale
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Kim M
authors.initials: KM
authors.lastname: Wilson
authors.forename: Hayley A
authors.initials: HA
authors.lastname: Croom
authors.forename: Scott
authors.initials: S
authors.lastname: Thomson
authors.forename: Barbara E H
authors.initials: BE
authors.lastname: Coupar
authors.forename: Alistair
authors.initials: A
authors.lastname: Ramsay
authors.forename: Damian F J
authors.initials: DF
authors.lastname: Purcell
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ffrench
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Ian A
authors.initials: IA
authors.lastname: Ramshaw
authors.forename: David B
authors.initials: DB
authors.lastname: Boyle
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: 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
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D018664:Interleukin-12