Poster Presentation Lorne Infection and Immunity 2013

The In-silico Identification of Epitopes Capable of inducing CD4 and CD8 responses in multiple mouse species. (#133)

Kristin Kirk 1 , Jake Rogers 1 , Jill Shaw 1 , Lara Grollo 1
  1. Swinburne University of Technology, Hawthorn, VIC, Australia

Enterovirus 71 (EV71) is an Enterovirus-A species belonging to the family Picornaviridae. Similarly to Polio, epidemics in the Asian-Pacific regions have prompted the need for fast and safer vaccination strategies. However, despite the success in the development of Polio vaccine, there is no licensed vaccine approved for EV71.

The identification of T-cell epitopes is of paramount importance in the establishment of protective immune responses. Using an in-silico reverse vaccination strategy, we have identified promiscuous CD4+ and CD8+ epitopes from virion VP1 and VP3 proteins. Our analysis included the complete set of H2 class I (H2-Kd, H2-Ld and H2-Dd) and class II (I-Ed and I-Ad) molecules. We have assessed the ability of the epitopes to induce broad T cell responses in the context of multiple HLA class II molecules that are represented by multiple strains of mice, namely;  the complex-2 (H2d) of the BALB/c mouse, the (H2b) of the C57BL/6 mice, and the (H2k) of the CBA mice.

As expected, mice varied in their IFN-y responses in the context of their respective MHC binding affinities. Two out of four CD8+ predicted epitopes produced a significant IFN-y response whereas three out of four CD4+ predicted epitopes produced significant responses. Furthermore, we found mice inoculated with the CD4+ epitopes were able to respond to CD8+ pulsed peptide, indicating that there is a shared core motif in MHC peptide recognition.

The ability to induce this response demonstrates the feasibility of induction of a broad immunological response in a diverse population as applicable to humans. These results may explain differences in T-cell epitope specificity as mediated by the MHC complex and provide insight into the development of epitope based vaccination strategies.