A CD46-binding Chimpanzee Adenovirus Vector as a Vaccine Carrier

• Published in: Molecular therapy Vol. 15; no. 3; pp. 608 - 617
• Main Authors: Tatsis, Nia, Blejer, Ariella, Lasaro, Marcio O, Hensley, Scott E, Cun, Ann, Tesema, Lello, Li, Yan, Gao, Guang-Ping, Xiang, Zhi Q, Zhou, Dongming, Wilson, James M, Ertl, Hildegund C J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2007; Elsevier Limited
• Subjects: Adenoviridae - genetics; Adenoviruses; Animals; Antibodies; Antibodies - immunology; Antigens; Blood; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Drug dosages; Gene therapy; Genetic Vectors - genetics; Humans; Lymphocytes; Membrane Cofactor Protein - genetics; Membrane Cofactor Protein - metabolism; Mice; Monkeys & apes; Pan troglodytes - genetics; Pan troglodytes - metabolism; Protein Binding; Sensitivity and Specificity; Transgenes - genetics; Transgenic animals; Vaccines; Vaccines - immunology; Vectors (Biology); Viruses; United States > US; Africa; Pennsylvania
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/sj.mt.6300078

A replication-defective chimeric vector based on the chimpanzee adenovirus serotype C1 was developed and tested as a vaccine carrier in mice. The AdC1 virus is closely related to human adenoviruses of subgroup B2 and uses CD46 for cell attachment. To overcome poor growth of E1-deleted AdC1 vectors on cell lines that provide the E1 of adenovirus of the human serotype 5 (AdHu5) virus in trans, the inverted terminal repeats and some of the early genes of AdC1 were replaced with those from AdC5, a chimpanzee origin adenovirus of subfamily E. The chimeric AdC1/C5 vector efficiently transduces CD46-expressing mouse dendritic cells (DCs) in vitro and initiates their maturation. Transduction of DCs in vivo is inefficient in CD46 transgenic mice. The AdC1/C5 vector induces transgene product-specific B- and CD8+ T-cell responses in mice. Responses are slightly higher in wild-type mice than in CD46 transgenic mice. Transgene product-specific T-cell responses elicited by the AdC1/C5 vector can be increased by priming or boosting with a heterologous adenovirus vector. Pre-existing immunity to adenovirus of the common human serotype 5 does not affect induction of cell-mediated immune responses by the AdC1/C5 vector. This vector provides an additional tool in a repertoire of adenovirus-based vaccine vectors.