TY - JOUR
T1 - Using HLA-A2.1 transgenic rabbit model to screen and characterize new HLA-A2.1 restricted epitope DNA vaccines
AU - Hu, Jiafen
AU - Schell, Todd D.
AU - Peng, Xuwen
AU - Cladel, Nancy M.
AU - Balogh, Karla K.
AU - Christensen, Neil D.
PY - 2010/10
Y1 - 2010/10
N2 - 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 fi ve 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 fi ve 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 identifi ed the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specifi c 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 fi ve epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specifi c 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.
AB - 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 fi ve 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 fi ve 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 identifi ed the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specifi c 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 fi ve epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specifi c 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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U2 - 10.4172/2157-7560.1000101
DO - 10.4172/2157-7560.1000101
M3 - Article
AN - SCOPUS:84858840553
SN - 2157-7560
VL - 1
JO - Journal of Vaccines and Vaccination
JF - Journal of Vaccines and Vaccination
IS - 1
ER -
