RRC ID 31869
Author Masuko K, Wakita D, Togashi Y, Kita T, Kitamura H, Nishimura T.
Title Artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP): preparation and immunological analysis of vaccine efficacy.
Journal Immunol Lett
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.
Volume 163(1)
Pages 102-12
Published 2015-1-1
DOI 10.1016/j.imlet.2014.11.016
PII S0165-2478(14)00295-8
PMID 25479286
MeSH Adjuvants, Immunologic / pharmacology* Animals Cancer Vaccines / chemistry Cancer Vaccines / immunology* Cell Line, Tumor Dendritic Cells / immunology Dendritic Cells / pathology Epitopes, T-Lymphocyte / chemistry Epitopes, T-Lymphocyte / immunology Epitopes, T-Lymphocyte / pharmacology* Humans Immunity, Cellular / drug effects Mice Neoplasms, Experimental / drug therapy* Neoplasms, Experimental / immunology Neoplasms, Experimental / pathology Oligodeoxyribonucleotides / pharmacology* Peptides / chemical synthesis Peptides / chemistry Peptides / immunology Peptides / pharmacology* Th1 Cells / immunology Th1 Cells / pathology
IF 3.276
Times Cited 5
Mice RBRC00144