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Using HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines

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Author(s): Dr. Jiafen Hu | Dr. Neil D. Christensen

Journal: Journal of Vaccines & Vaccination
ISSN 2157-7560

Volume: 1;
Issue: 1;
Date: 2010;
Original page

Keywords: HLA-A2.1 transgenic mouse and rabbit | Epitope DNA vaccine | T cell mediated immune responses | Gene-gun | Protective and therapeutic immunity | CRPV

ABSTRACT
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 specifi c 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.
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