Strong and Specific Protective and Therapeutic Immunity Induced by Single HLA-A2.1 Restricted Epitope DNA Vaccine in Rabbits

An HLA-A2.1 transgenic rabbit /Cottontail rabbit papillomavirus (CRPV) infection model has been reported previously. In this study, we incorporated online MHCI epitope prediction software and HLA-A2.1 transgenic mouse and rabbit systems together to demonstrate an efficient way to identify and test immunogenicity of two HLA-A2.1 restricted epitopes from CRPVE1 (161-169 LLFRQAHSV and 303-311 MLQEKPFQL). Both epitopes were able to induce specific cytotoxic CD8 T cells in HLA-A2.1 mice and rabbits after peptide and DNA immunization and in vitro stimulation respectively. Using an epitope DNA vaccination method, we achieved partial and complete protection against CRPV DNA challenge by CRPVE1/161-169 and CRPVE1/303-311 respectively in HLA-A2.1 transgenic outbred rabbits. CRPVE1/303-311 also showed strong and specific therapeutic effects in CRPV-infected HLA-A2.1 transgenic outbred rabbits. Interestingly, epitope CRPVE1/303-311 (but not E1/161-169) showed strong protective immunity in non-transgenic EIII/JC inbred (but not outbred) NZW rabbits. Our data demonstrates an efficient way to identify HLA-A2.1 restricted epitopes for the development of prophylactic and therapeutic vaccines.