title: Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic rabbits.
abstract: 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, E1peptide 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 mediate 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.
authors.affiliation: Jake Gittlen Cancer Research Foundation, Pennsylvania State University college of medicine, Hershey, PA 17033, USA ; Department of Pathology, Pennsylvania State University college of medicine, Hershey, PA 17033, USA.
authors.forename: Jiafen
authors.initials: J
authors.lastname: Hu
authors.affiliation: Jake Gittlen Cancer Research Foundation, Pennsylvania State University college of medicine, Hershey, PA 17033, USA ; Department of Pathology, Pennsylvania State University college of medicine, Hershey, PA 17033, USA.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Budgeon
authors.affiliation: Jake Gittlen Cancer Research Foundation, Pennsylvania State University college of medicine, Hershey, PA 17033, USA ; Department of Pathology, Pennsylvania State University college of medicine, Hershey, PA 17033, USA.
authors.forename: Karla K
authors.initials: KK
authors.lastname: Balogh
authors.affiliation: Department of Comparative Medicine, Pennsylvania State University college of medicine, Hershey, PA 17033, USA.
authors.forename: Xuwen
authors.initials: X
authors.lastname: Peng
authors.affiliation: Jake Gittlen Cancer Research Foundation, Pennsylvania State University college of medicine, Hershey, PA 17033, USA ; Department of Pathology, Pennsylvania State University college of medicine, Hershey, PA 17033, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Cladel
authors.affiliation: Jake Gittlen Cancer Research Foundation, Pennsylvania State University college of medicine, Hershey, PA 17033, USA ; Department of Pathology, Pennsylvania State University college of medicine, Hershey, PA 17033, USA ; Microbiology and Immunology, Pennsylvania State University college of medicine, Hershey, PA 17033, USA.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Christensen
keywords: CD4+ T cells; CD8+ T cells; CRPV; HLA-A2.1; Long peptide; T-cell mediated immune response; TT helper; animal model; therapeutic vaccine; transgenic rabbit; viral infection