title: Immunization with antigenic peptides complexed with β-glucan induces potent cytotoxic T-lymphocyte activity in combination with CpG-ODNs.
abstract: The induction of antigen-specific immune responses requires immunization with not only antigens, but also adjuvants. CpG oligonucleotides (CpG-ODNs) are well-known ligands for Toll-like receptor 9 and a potent adjuvant that induces both Th1-type humoral and cellular immune responses including cytotoxic T-lymphocyte responses. We previously demonstrated that β-glucan schizophyllan (SPG) can form complexes with CpG-ODNs with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses by co-administration of antigenic proteins, namely ovalbumin (OVA). Immunization with antigenic peptides, OVA257-264, did not induce these antigen-specific immune responses even in combination with CpG-dA/SPG, indicating that peptides require a carrier to antigen presenting cells. In this study, we prepared conjugates comprising OVA257-264 and dA40, and made complexes with SPG. Immunization with OVA257-264-dA/SPG induced peptide-specific immune responses in combination with CpG-dA regardless of complexation with SPG both in vitro and in vivo. When splenocytes from immunized mice were incubated with E.G7-OVA tumor model cells presenting OVA peptides, the number of cells drastically decreased after 24h. Furthermore, mice pre-immunized with OVA257-264-dA/SPG and CpG-ODNs exhibited a long delay in tumor growth after tumor inoculation. Therefore, these peptide-dA/SPG and CpG-dA/SPG complexes could be used as a potent vaccine for the treatment of cancers and infectious diseases.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan. Electronic address: mochizuki@kitakyu-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mochizuki
authors.affiliation: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Morishita
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8, Asagi Saito, Ibaraki, Osaka 567-0085, Japan; Laboratory of Vaccine Science, Immunology Frontier Research Center (iFReC), Osaka University, 1-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobiyama
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8, Asagi Saito, Ibaraki, Osaka 567-0085, Japan; Laboratory of Vaccine Science, Immunology Frontier Research Center (iFReC), Osaka University, 1-1, Yamadaoka, Suita, Osaka 565-0871, Japan; Vaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases (RIMD), Osaka University, 1-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Aoshi
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8, Asagi Saito, Ibaraki, Osaka 567-0085, Japan; Laboratory of Vaccine Science, Immunology Frontier Research Center (iFReC), Osaka University, 1-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.affiliation: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan. Electronic address: sakurai@kitakyu-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakurai
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D002478:Cells, Cultured; D007114:Immunization; D008213:Lymphocyte Activation / Q000187:drug effects*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D012566:Sizofiran / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; C110366:OVA-8; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D012566:Sizofiran; D010047:Ovalbumin
keywords: Antigen presenting cell; Cancer vaccine; CpG-ODN; Peptide vaccine; β-Glucan