CONSTRUCTION AND CHARACTERIZATION OF HEXON-CHIMERIC ADENOVIRUSES - SPECIFICATION OF ADENOVIRUS SEROTYPE

This study has used the strategy of gene replacement to characterize t he contribution of the adenovirus (Ad) capsid protein hexon to serotyp e definition. By replacing the Ad type 5 (Ad5) hexon gene with sequenc es from Ad2, we have changed the type specificity of the chimeric viru s. The type-determining epitopes are primarily associated with loop 1 of hexon and, to a much lesser degree, with loop 2. In spite of the se rotype distinctiveness of the chimeric hexon viruses, epitope similari ty between the vectors resulted in a low level of cross-reactive neutr alizing antibody, which in combination with activated cellular and inn ate arms of the immune system is sufficient to suppress gene transduct ion following readministration in vivo.