title: Activation of dendritic cell function by soypeptide lunasin as a novel vaccine adjuvant.
abstract: The addition of an appropriate adjuvant that activates the innate immunity is essential to subsequent development of the adaptive immunity specific to the vaccine antigens. Thus, any innovation capable of improving the immune responses may lead to a more efficacious vaccine. We recently identified a novel immune modulator using a naturally occurring seed peptide called lunasin. Lunasin was originally isolated from soybeans, and it is a small peptide containing 43 amino acids. Our studies revealed stimulatory effects of lunasin on innate immune cells by regulating expression of a number of genes that are important for immune responses. The objective was to define the effectiveness of lunasin as an adjuvant that enhances immune responses. The immune modulating functions of lunasin were characterized in dendritic cells (DCs) from human peripheral blood mononuclear cells (PBMCs). Lunasin-treated conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86, CD40) but also exhibited up-regulation of cytokines (IL1B, IL6) and chemokines (CCL3, CCL4). Lunasin-treated cDCs induced higher proliferation of allogeneic CD4+ T cells when comparing with medium control treatment in the mixed leukocyte reaction (MLR). Immunization of mice with ovalbumin (OVA) and lunasin inhibited the growth of OVA-expressing A20 B-lymphomas, which was correlated with OVA-specific CD8+ T cells. In addition, lunasin was an effective adjuvant for immunization with OVA, which together improved animal survival against lethal challenge with influenza virus expressing the MHC class I OVA peptide SIINFEKL (PR8-OTI). These results suggest that lunasin may function as a vaccine adjuvant by promoting DC maturation, which in turn enhances the development of protective immune responses to the vaccine antigens.
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, IN, United States.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Tung
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, IN, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Lewis
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, IN, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, IN, United States.
authors.forename: Morayo
authors.initials: M
authors.lastname: Jaja
authors.affiliation: HB Wells Center for Pediatric Research, Departments of Pediatrics and Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, IN, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Bone Marrow and Stem Cell Transplantation Program, Lymphoma Program, Division of Hematology/Oncology, Indiana University School of Medicine, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Robertson
authors.affiliation: HB Wells Center for Pediatric Research, Departments of Pediatrics and Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhou
authors.affiliation: HB Wells Center for Pediatric Research, Departments of Pediatrics and Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, IN, United States. Electronic address: huchang@iupui.edu.
authors.forename: Hua-Chen
authors.initials: HC
authors.lastname: Chang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D010047:Ovalbumin; D030262:Soybean Proteins / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; C120514:GM2S-1 protein, soybean; D030262:Soybean Proteins; D010047:Ovalbumin
keywords: DC maturation; Immune modulating agent; Lunasin; Vaccine adjuvant