Using this antigen capsid-incorporation strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. The major capsid protein hexon has been utilized for these antigen capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion [4, 14, 15, [17] [18] [19] [20] [21] . Of note, our previous work has shown that we can incorporate small heterologous peptides into Ad hexon hypervariable regions (HVRs) without perturbing viral viability and other biological characteristics [19] . Published studies have focused on antigen and/or epitope incorporations at HVR5 or single site antigen/epitope incorporation at fiber or protein IX (pIX) [22] . In this regard, antigenic epitopes including linker sequences ranging in size from nine to forty-five amino acids have been incorporated within the Ad5 hexon region or Ad2 hexon region. These epitope incorporations include epitopes derived from polio, Pseudomonas aeruginosa, B. anthracis, and HIV as well as model epitopes [4, 15, 16, 18] . Based on our ability to manipulate both HVR2 and HVR5 sites, recently we sought to explore the relative merits of antigen incorporation within these two hexon locales. In order to accomplish this we compared the flexibility and capacity of HVR2 and HVR5, respectively. We genetically incorporated identical model epitopes of increasing size within HVR2 or HVR5 of the Ad5 hexon. Our previous study demonstrated that hexonincorporated model antigens elicit a range of immune responses depending on antigen placement or antigen size at either the HVR2 or HVR5 locales. This study confirmed that HVR2 could be a potential incorporation site for antigens of considerable size and that vaccination with vectors that display incorporations at HVR2 is feasible for vaccine development [16] .