Induction of CD8+ T Cells to an HIV-1 Antigen through a Prime Boost Regimen with Heterologous E1-Deleted Adenoviral Carriers This information is current as of October 2, 2021. Arguinaldo R. Pinto, Julie C. Fitzgerald, Wynetta Giles-Davis, Guang Ping Gao, James M. Wilson and Hildegund C. J. Ertl J Immunol 2003; 171:6774-6779; ;

doi: 10.4049/jimmunol.171.12.6774 Downloaded from http://www.jimmunol.org/content/171/12/6774

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Induction of CD8؉ T Cells to an HIV-1 Antigen through a Prime Boost Regimen with Heterologous E1-Deleted Adenoviral Vaccine Carriers1

Arguinaldo R. Pinto,* Julie C. Fitzgerald,*† Wynetta Giles-Davis,* Guang Ping Gao,† James M. Wilson,† and Hildegund C. J. Ertl2*

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 neu tralizing Abs due to natural exposures to AdHu5 virus. To circumvent reduction of the efficacy of adenovirus (Ad) vector-based by neutralizing Abs to the vaccine carrier, we developed E1-deleted adenoviral vaccine carriers based on simian sero- types. 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 Downloaded from 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 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 with an E1-deleted Ad vector followed by booster http://www.jimmunol.org with a poxvirus vector and they surpass regimens based on DNA vaccine prime followed by a recombinant ad- enoviral vector boost. The Journal of Immunology, 2003, 171: 6774–6779.

ach day, on average, 15,000 humans are newly infected served internal proteins, provide an alternative strategy which is with the HIV-1. Although efficacious antiviral therapies unlikely to induce sterilizing immunity to HIV-1 but might control E are avail