A CD46-binding chimpanzee adenovirus vector as a vaccine carrier.
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.
Tatsis
Nia
N
1The Wistar Institute, Philadelphia, Pennsylvania, USA.
Blejer
Ariella
A
Lasaro
Marcio O
MO
Hensley
Scott E
SE
Cun
Ann
A
Tesema
Lello
L
Li
Yan
Y
Gao
Guang-Ping
GP
Xiang
Zhi Q
ZQ
Zhou
Dongming
D
Wilson
James M
JM
Ertl
Hildegund C J
HC
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D002679:Pan troglodytes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012680:Sensitivity and Specificity; D019076:Transgenes / Q000235:genetics; D014612:Vaccines / Q000276:immunology*
D000906:Antibodies; D051916:Membrane Cofactor Protein; D014612:Vaccines