Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic rabbits

作     者：Hu, Jiafen Budgeon, Lynn R. Balogh, Karla K. Peng, Xuwen Cladel, Nancy M. Christensen, Neil D. 

作者机构：Jake Gittlen Cancer Research Foundation Pennsylvania State University College of Medicine Hershey PA 17033 United States Department of Pathology Pennsylvania State University College of Medicine Hershey PA 17033 United States Department of Comparative Medicine Pennsylvania State University College of Medicine Hershey PA 17033 United States Microbiology and Immunology Pennsylvania State University College of Medicine Hershey PA 17033 United States 

出 版 物：《Trials in Vaccinology》 (Trails Vaccinology)

年 卷 期：2014年第3卷第1期

页      面：134-142页

基　　金：National Institutes of Health, NIH National Cancer Institute, NCI, (R01 CA47622) National Cancer Institute, NCI 

主　　题：CRPV HLA-A2.1 Long peptide T-cell mediated immune response Therapeutic vaccine Transgenic rabbit 

摘      要：Long peptide immunization is a promising strategy to clear established tumors. In the current study, we investigated the therapeutic effect of a naturally existing long peptide that contained two HLA-A2.1 restricted epitopes (CRPVE1/149-157 and CRPVE1/161-169) from cottontail rabbit papillomavirus (CRPV) E1 using our CRPV/HLA-A2.1 transgenic rabbit model. A universal Tetanus Toxin helper motif (TT helper) was tagged at either the N-terminus or the carboxyl-terminus of this long peptide and designated as TT-E1 peptide and E1 peptide-TT, respectively. Four groups of HLA-A2.1 transgenic rabbits were infected with wild type CRPV DNA. Three weeks post-infection, the rabbits were immunized four times with TT-E1 peptide, E1 peptide only, E1 peptide-TT or TT-control peptide with two-week intervals between immunizations. Tumor outgrowth was monitored and recorded weekly. After the third booster immunization, tumors on two of the four E1 peptide-TT immunized rabbits began to shrink. One animal from this group was free of tumors at the termination of the study. The mean papilloma size of E1 peptide-TT immunized rabbits was significantly smaller when compared with that of the three other groups (P 0.05, one way ANOVA analysis). It is interesting that E1 peptide-TT vaccination not only stimulated stronger T cell mediated immune responses but also stronger antibody generations. We conclude that the location of a TT helper motif tagged at the long peptide vaccine is critical for the outcome of therapeutic responses to persistent tumors in our HLA-A2.1 transgenic rabbit model. © 2014 The Authors. Published by Elsevier Ltd.