The efficacy of recombinant adenoviruses (Ads) vaccine vectors is diminished by the high prevalence of anti-Ad antibodies (Abs) that hampers gene transfer. Epitope display on Ad capsid constitutes an alternative approach to bypass anti-Ad Ab capacity from blocking antigen expression. To understand the role of the epitope insertion site, an ovalbumin-derived epitope was genetically inserted into either Ad hexon or fiber proteins. Hexon-modified Ads triggered higher anti-ovalbumin Ab responses after one injection but surprisingly fiber-modified Ads were by far more potent after two or several administrations. Our data unravel a role for anti-Ad humoral immunity in controlling anti-epitope humoral responses.
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