Characterization of a family of chimpanzee adenoviruses and development of molecular clones for gene transfer vectors.
The high prevalence of preexisting immunity to the commonly used adenoviral vectors, as well as the requirement for readministration of vector for multiple therapeutic applications, necessitates the development of a panel of immunologically distinct adenoviral vectors against which neutralizing antibodies are rare in human populations. We have completely sequenced three chimpanzee-derived adenoviruses, Pan 5, Pan 6, and Pan 7, and have molecularly cloned E1-deleted vector genomes from each as bacterial plasmids. All the E1-deleted vectors were grown to high titer in HEK 293 cells. Neutralizing antibodies to the chimpanzee adenoviral vectors were not detected in serum samples from human subjects. In vitro cross-neutralization using rabbit antisera and in vivo readministration experiments in mice demonstrated that antibodies against Pan 5, Pan 7, or Pan 9 cross-neutralize one another but do not neutralize Pan 6. These results indicate that chimpanzee adenoviral vectors may be useful as vaccines or gene therapy vectors in human populations and should allow applications that require multiple vector administrations.
Roy
Soumitra
S
Department of Medicine, University of Pennsylvania and the Wistar Institute, Philadelphia, PA 19104, USA.
Gao
Guangping
G
Lu
You
Y
Zhou
Xiangyang
X
Lock
Martin
M
Calcedo
Roberto
R
Wilson
James M
JM
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D017498:Adenovirus E1 Proteins / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D004279:DNA, Viral / Q000235:genetics; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D005814:Genes, Viral; D005822:Genetic Vectors / Q000276:immunology*; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009500:Neutralization Tests; D002679:Pan troglodytes; D011817:Rabbits; D017422:Sequence Analysis, DNA; D014161:Transduction, Genetic
D017498:Adenovirus E1 Proteins; D004279:DNA, Viral; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins