Evaluation of adenovirus vectors containing serotype 35 fibers for vaccination.
In contrast to commonly used serotype 5-based adenovirus (Ad) vectors, Ad's containing fibers derived from B-group serotype 35 (Ad5/35) efficiently transduce human DCs ex vivo and appear to target antigen-presenting cells after intravenous injection into baboons. Based on this, Ad5/35 vectors could be valuable tools for immunotherapy and vaccination. On the other hand, a number of studies indicate that signaling through the B-group Ad receptor, CD46, can cause tolerance or immunosuppression. Since mice do not express CD46 in a human-like pattern, we studied the in vivo properties of Ad5/35 in transgenic mice that express CD46 in a pattern and at a level similar to those of humans. Hypersensitivity assays and analyses of frequencies of regulatory T cells and T cell responses did not indicate that Ad5/35 injection exerts detrimental effects on the host's immune system. An Ad5/35 vector expressing a model antigen was able to trigger a strong T cell response against the test antigen after intramuscular injection. Overall, compared to Ad5 vectors, Ad5/35 vectors had a better safety profile, reflected by lower serum levels of proinflammatory cytokines.
DiPaolo
Nelson
N
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Ni
Shaoheng
S
Gaggar
Anuj
A
Strauss
Robert
R
Tuve
Sebastian
S
Li
Zong Yi
ZY
Stone
Daniel
D
Shayakhmetov
Dmitry
D
Kiviat
Nancy
N
Touré
Papa
P
Sow
Salif
S
Horvat
Branka
B
Lieber
André
A
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology*; D016679:Genome, Viral; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051916:Membrane Cofactor Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes; D014611:Vaccination; D014765:Viral Vaccines
D051916:Membrane Cofactor Protein; D014765:Viral Vaccines; D049452:Green Fluorescent Proteins