Session 53Poster Presentations DNA Vaccines Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall D
453a Magnitude and Diversity of Cytotoxic T-lymphocyte Responses Elicited by Multiepitope DNA Vaccination in Rhesus Monkeys R A Subbramanian*, M J Kuroda, W A Charini, D H Barouch, C Costantino, S Santra, J E Schmitz, J W Shiver, N L Letvin Harvard Medical School, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Background: During the course of HIV/SIV infection, CTL responses develop a predictable bias in their pattern of epitope recognition with most of the CTL response being focused on only a very limited number of epitopes. Accumulating evidence suggests that an effective HIV vaccine must elicit a high frequency CTL response against the greatest possible diversity of viral epitopes.
Methods: We systematically assessed two prototype mult-iepitope plasmid DNA vaccines in the simian human immunodeficiency virus (SHIV)/ rhesus monkey model to determine their efficiency in priming for dominant and subdominant epitopes restricted by the same MHC Class I allele, Mamu-A*01.
Results: While a simple multi-epitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multi-epitope genetic sequence inserted into an immunogenic SIV gag DNA vaccine elicited high frequency epitope-specific CTL responses. Both multi-epitope vaccine prototypes primed for robust epitope-specific CTL responses that developed following boosting with recombinant MVA vaccines expressing complete viral proteins. However, the natural hierarchy of immunodominance for these epitopes re-emerged in the boosted monkeys.
Conclusions: These studies suggest that multi-epitope plasmid DNA vaccines can efficiently prime for CTL responses of increased breadth, but that established boosting regimens do not overcome predicted hierarchies of immunodominance.
