title: Multigene DNA priming-boosting vaccines protect macaques from acute CD4+-T-cell depletion after simian-human immunodeficiency virus SHIV89.6P mucosal challenge.
abstract: We evaluated four priming-boosting vaccine regimens for the highly pathogenic simian human immunodeficiency virus SHIV89.6P in Macaca nemestrina. Each regimen included gene gun delivery of a DNA vaccine expressing all SHIV89.6 genes plus Env gp160 of SHIV89.6P. Additional components were two recombinant vaccinia viruses, expressing SHIV89.6 Gag-Pol or Env gp160, and inactivated SHIV89.6 virus. We compared (i) DNA priming/DNA boosting, (ii) DNA priming/inactivated virus boosting, (iii) DNA priming/vaccinia virus boosting, and (iv) vaccinia virus priming/DNA boosting versus sham vaccines in groups of 6 macaques. Prechallenge antibody responses to Env and Gag were strongest in the groups that received vaccinia virus priming or boosting. Cellular immunity to SHIV89.6 peptides was measured by enzyme-linked immunospot assay; strong responses to Gag and Env were found in 9 of 12 vaccinia virus vaccinees and 1 of 6 DNA-primed/inactivated-virus-boosted animals. Vaccinated macaques were challenged intrarectally with 50 50% animal infectious doses of SHIV89.6P 3 weeks after the last immunization. All animals became infected. Five of six DNA-vaccinated and 5 of 6 DNA-primed/particle-boosted animals, as well as all 6 controls, experienced severe CD4(+)-T-cell loss in the first 3 weeks after infection. In contrast, DNA priming/vaccinia virus boosting and vaccinia virus priming/DNA boosting vaccines both protected animals from disease: 11 of 12 macaques had no loss of CD4(+) T cells or moderate declines. Virus loads in plasma at the set point were significantly lower in vaccinia virus-primed/DNA-boosted animals versus controls (P = 0.03). We conclude that multigene vaccines delivered by a combination of vaccinia virus and gene gun-delivered DNA were effective against SHIV89.6P viral challenge in M. nemestrina.
authors.affiliation: Seattle Biomedical Research Institute, University of Washington, Seattle, Washington 98109, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Doria-Rose
authors.forename: C
authors.initials: C
authors.lastname: Ohlen
authors.forename: P
authors.initials: P
authors.lastname: Polacino
authors.forename: C C
authors.initials: CC
authors.lastname: Pierce
authors.forename: M T
authors.initials: MT
authors.lastname: Hensel
authors.forename: L
authors.initials: L
authors.lastname: Kuller
authors.forename: T
authors.initials: T
authors.lastname: Mulvania
authors.forename: D
authors.initials: D
authors.lastname: Anderson
authors.forename: P D
authors.initials: PD
authors.lastname: Greenberg
authors.forename: S-L
authors.initials: SL
authors.lastname: Hu
authors.forename: N L
authors.initials: NL
authors.lastname: Haigwood
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019470:Biolistics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007117:Immunization, Secondary; D008254:Macaca nemestrina; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D019302:HIV Envelope Protein gp160; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins