Comparison of adenoviruses from species B, C, E, and F after intravenous delivery.
Recent attempts to circumvent the limitations of adenovirus (Ad) vectors derived from species C serotype Ad5 have focused on the use of alternative human serotypes. These new serotypes have multiple benefits including a low prevalence of neutralizing antibodies in humans and alternate tropisms. To investigate the characteristics of alternatives to Ad5 vectors, we compared the biodistribution and safety of Ads from species B (Ad3, 11p, 35), C (Ad5), E (Ad4), and F (Ad41), or chimeric Ad5 viruses containing the Ad11 or Ad35 fibers (Ad5/11 and Ad5/35), after intravenous (IV) delivery into hCD46 transgenic mice. Our data suggest that (i) mechanisms of cell and tissue sequestration differ; (ii) levels of sequestration to lung, liver, or spleen do not correlate with toxicity; (iii) delivery of all serotypes causes activation of coagulation, possibly through platelet interaction; (iv) despite binding to the same receptor in vitro, Ad serotypes act differently in vivo; and (v) platelet depletion affects blood clearance, organ sequestration and chemokine/cytokine release of some, but not all Ad serotypes. Overall, our data indicate that Ad5-based vectors are relatively safe as compared to other serotypes. This data should be taken into consideration in future studies about the clinical use of Ad vectors.
Stone
Daniel
D
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.
Liu
Ying
Y
Li
Zong-Yi
ZY
Tuve
Sebastian
S
Strauss
Robert
R
Lieber
André
A
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008854:Microscopy, Electron; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D013045:Species Specificity
D000914:Antibodies, Viral; D017931:DNA Primers