Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model.
Cottontail rabbit papillomavirus (CRPV)/rabbit model is widely used to study pathogenesis of papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection. J Immunol 2006;177(11):8037-45]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPVE1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic rabbits, respectively, by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic rabbits from both genetic backgrounds but not in the control-vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software.
Hu
Jiafen
J
Jake Gittlen Cancer Research Foundation, Department of Pathology, Pennsylvania State University college of medicine, Hershey, PA 17033, USA.
Cladel
Nancy
N
Peng
Xuwen
X
Balogh
Karla
K
Christensen
Neil D
ND
D000818:Animals; D030801:Animals, Genetically Modified; D012777:Cottontail rabbit papillomavirus / Q000276:immunology*; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000235:genetics*; D007115:Immunization Schedule; D007271:Injections, Intradermal; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage*; D011817:Rabbits; D019444:Vaccines, DNA / Q000008:administration & dosage; D014764:Viral Proteins / Q000276:immunology*
D000939:Epitopes; D015789:HLA-A2 Antigen; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins