We have developed novel Ad vectors that have the potential to optimize Ad vaccine approaches. This strategy involves inserting antigenic epitopes into HVR2 or HVR5 regions of the Ad capsid protein, hexon, to stimulate epitope-specific antibody responses following vaccination. This method offers the ability to compare a range of identical epitopes incorporated within HVRs for antigenic optimization. Our current study is the first of its kind to genetically incorporate HIV antigen within the Ad5 hexon HVR2 alone or in combination with genomic incorporation of a transgene for HIV antigen expression. In this study we successfully incorporated the HIV MPER in the Ad5 HVR2 region as evidenced by PCR, Western blot analysis, and the purified, wholevirus ELISAs (Figures 1,2, and 3) .