title: Induction of CD8+ T cells to an HIV-1 antigen through a prime boost regimen with heterologous E1-deleted adenoviral vaccine carriers.
abstract: E1-deleted adenoviral recombinants most commonly based on the human serotype 5 (AdHu5) have been shown thus far to induce unsurpassed transgene product-specific CD8(+) T cell responses. A large percentage of the adult human population carries neutralizing Abs due to natural exposures to AdHu5 virus. To circumvent reduction of the efficacy of adenovirus (Ad) vector-based vaccines by neutralizing Abs to the vaccine carrier, we developed E1-deleted adenoviral vaccine carriers based on simian serotypes. One of these carriers, termed AdC68, expressing a codon-optimized truncated form of gag of HIV-1 was shown previously to induce a potent transgene product-specific CD8(+) T cell response in mice. We constructed a second chimpanzee adenovirus vaccine vector, termed AdC6, also expressing the truncated gag of HIV-1. This vector, which belongs to a different serotype than the AdC68 virus, induces high frequencies of gag-specific CD8(+) T cells in mice including those pre-exposed to AdHu5 virus. Generation of an additional E1-deleted adenoviral vector of chimpanzee origin allows for sequential booster immunizations with heterologous vaccine carriers. In this study, we show that such heterologous prime boost regimens based on E1-deleted adenoviral vectors of different serotypes expressing the same transgene product are highly efficient in increasing the transgene product-specific CD8(+) T cell response. They are equivalent to sequential vaccinations with an E1-deleted Ad vector followed by booster immunization with a poxvirus vector and they surpass regimens based on DNA vaccine prime followed by a recombinant adenoviral vector boost.
authors.affiliation: The Wistar Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Arguinaldo R
authors.initials: AR
authors.lastname: Pinto
authors.forename: Julie C
authors.initials: JC
authors.lastname: Fitzgerald
authors.forename: Wynetta
authors.initials: W
authors.lastname: Giles-Davis
authors.forename: Guang Ping
authors.initials: GP
authors.lastname: Gao
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017498:Adenovirus E1 Proteins / Q000235:genetics / Q000276:immunology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D015488:HIV Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D002679:Pan troglodytes; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D017498:Adenovirus E1 Proteins; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015488:HIV Antigens; D019444:Vaccines, DNA