title: Artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP): preparation and immunological analysis of vaccine efficacy.
abstract: To elucidate the immunologic mechanisms of artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP), which indicated a great vaccine efficacy in human cancers, we prepared ovalbumin (OVA)-H/K-HELP by conjugating killer and helper epitopes of OVA-model tumor antigen via a glycine-linker. Vaccination of C57BL/6 mice with OVA-H/K-HELP (30 amino acids) but not with short peptides mixture of class I-binding peptide (8 amino-acids) and class II-binding peptide (17 amino-acids) combined with adjuvant CpG-ODN (cytosine-phosphorothioate-guanine oligodeoxynucleotides), induced higher numbers of OVA-tetramer-positive CTL with concomitant activation of IFN-γ-producing CD4(+) Th1 cells. However, replacement of glycine-linker of OVA-H/K-HELP with other peptide-linker caused a significant decrease of vaccine efficacy of OVA-H/K-HELP. In combination with adjuvant CpG-ODN, OVA-H/KHELP exhibited greater vaccine efficacy compared with short peptides vaccine, in both preventive and therapeutic vaccine models against OVA-expressing EG-7 tumor. The elevated vaccine efficacy of OVAH/K-HELP might be derived from the following mechanisms: (i) selective presentation by only professional dendritic cells (DC) in vaccinated draining lymph node (dLN); (ii) a long-term sustained antigen presentation exerted by DC to stimulate both CTL and Th1 cells; (iii) formation of three cells interaction among DC, Th and CTL. In comparative study, H/K-HELP indicated stronger therapeutic vaccine efficacy compared with that of extended class I synthetic long peptide, indicating that both the length of peptide and the presence of Th epitope peptide were crucial aspects for preparing artificially synthesized H/K-HELP vaccine.
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Masuko
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Daiko
authors.initials: D
authors.lastname: Wakita
authors.affiliation: Bioimmulance Co. Ltd., Sapporo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan; Division of ROYCE' Health Bioscience, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kita
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan; Division of ROYCE' Health Bioscience, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan. Electronic address: tak24@igm.hokudai.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D009838:Oligodeoxyribonucleotides; D010455:Peptides
keywords: Cytotoxic T cells; Dendritic cells; H/K-HELP; Helper T cells; Long peptide vaccine; Tumor vaccine therapy