Open AccessUsing HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines
Author(s) -
Jiafen Hu,
Todd D. Schell,
Xuwen Peng,
Nancy M. Cladel,
Karla K. Balogh,
Neil D. Christensen
Publication year - 2010
Publication title -
journal of vaccines and vaccination
Language(s) - English
Resource type - Journals
ISSN - 2157-7560
DOI - 10.4172/2157-7560.1000101
Subject(s) - epitope , biology , dna vaccination , transgene , virology , genetically modified mouse , immunization , immunology , antigen , gene gun , human leukocyte antigen , immunity , microbiology and biotechnology , immune system , gene , genetics
We have established an HLA-A2.1 transgenic rabbit /cottontail rabbit papillomavirus (CRPV) infection model. Using this novel transgenic animal model, we reported earlier that a multivalent epitope DNA vaccine (CRPVE1ep1-5) containing five HLA-A2.1 restricted epitopes from CRPVE1 (42-50, 149-157, 161-169, 245-253 and 303-311) was successful in providing strong and specific protective and therapeutic immunity. Among these five epitopes, two (161-169 and 303-311) have been proven to stimulate strong immunity in both HLA-A2.1 transgenic mouse and rabbit models. In the current study, we further identified the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specific CTL responses in HLA-A2.1 transgenic mice by DNA immunization but undetectable by peptide immunization. CRPVE1/42-50 and 245-253 failed to respond in HLA-A2.1 transgenic mice either by peptide or DNA immunization. All the three epitopes when administrated as DNA vaccines, however, were able to stimulate strong protective immunity in HLA-A2.1 transgenic rabbits in a dose dependent manner. Among the five epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specific therapeutic effects in CRPV-infected HLA-A2.1 transgenic rabbits. Taken together, the HLA-A2.1 transgenic rabbit model recognized more epitopes than did the HLA-A2.1 transgenic mouse model. Our data demonstrate that the HLA-A2.1 transgenic rabbit model can complement the HLA-A2.1 transgenic mouse model for the development and testing of new HLA-A2.1 restricted prophylactic and therapeutic T cell based DNA vaccines.