title: An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge.
abstract: One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV(mac)251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV(mac)251 challenge. Peak control correlated with the expansion of HLA-DR(+) CD8(+) T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA, United States.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Hutnick
authors.forename: Devin J F
authors.initials: DJ
authors.lastname: Myles
authors.forename: Lauren
authors.initials: L
authors.lastname: Hirao
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Scott
authors.forename: Bernadette
authors.initials: B
authors.lastname: Ferraro
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bett
authors.forename: Danilo
authors.initials: D
authors.lastname: Casimiro
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Kim
authors.forename: John
authors.initials: J
authors.lastname: Shiver
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D007117:Immunization, Secondary / Q000379:methods*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D018449:SAIDS Vaccines; D019444:Vaccines, DNA