Characterization of malleability and immunological properties of human adenovirus type 3 hexon hypervariable region 1.

Adenovirus (Ad) capsids that display exogenous epitopes can be potently immunogenic, eliciting a potent humoral response against components of the capsid. We used the epitopes flag, his(6)flag, his(6)lgsflag and AdV4HVR5 as model antigens to characterize the hexon hypervariable region (HVR) 1 as a site for epitope insertion. A peptide of up to 17 amino acids could be incorporated into HVR1 of the Ad3 hexon without adversely affecting the biological characteristics of the virus. Multiple vaccinations with capsid-modified Ad3 induced a humoral response against the epitope inserted in HVR1. However, antiserum against the his(6)flag or his(6)lgsflag epitope did not recognize glutathione S-transferase (GST)-his(6) and GST-flag fusion protein. Our study illustrates that there is an immune response against the new epitope within the amino acids of his(6)flag or his(6)lgsflag epitopes. This discovery could be a warning for the generation of multivalent vaccine vectors by incorporation of multiple epitopes into single HVRs.