It is more than likely that the MPER epitope inserted into the Ad hexon is not presenting in the same conformation as it would be presented within the context of an HIV virion, therefore there are advantages and disadvantages to the antigen capsid-incorporation approach. The advantages of this approach include the fact that it is obviously much easier to insert a small peptide from HIV into hexon as compared to inserting a correctly folded version of the full HIV protein into hexon (which would likely be impossible). However, despite the fact that the MPER presentation might be different with respect to Ad capsid incorporation compared to that of MPER expressed on the HIV virion, we were able to detect the presence of this epitope by the means of human HIV monoclonal antibody 2F5, which recognizes 14 amino acids within MPER ( Figures 2B and 3) . Whereas, we were not able to detect the presence of MPER with the use of human HIV monoclonal antibody 4E10, which binds a 6 amino acid linear epitope immediately C-terminal to the 2F5 epitope and contained with MPER (data not shown). These observations suggest that the MPER conformation is similar but not identical to that presented by the HIV virion. One advantage of the antigen capsidincorporation approach is that the non-glycosylated MPER may be more immunogenic because of the absence of glycan-shielding. With the hexon/peptide presentation approach we should be able to address additional interesting questions, e.g. are there any glycosylation sites within or around the MPER region that affect immunogenicity. We plan to rigorously examine the ability of the peptide presentation approach to produce neutralizing antibodies, perhaps in a guinea pig or rabbit system.