RRC ID 36892
Author Li HS, Piao DC, Jiang T, Bok JD, Cho CS, Lee YS, Kang SK, Choi YJ.
Title Recombinant interleukin 6 with M cell-targeting moiety produced in Lactococcus lactis IL1403 as a potent mucosal adjuvant for peroral immunization.
Journal Vaccine
Abstract Development and application of safe and effective mucosal adjuvants are important to improve immunization efficiency in oral vaccine. Here, we report a novel mucosal adjuvant, IL-6-CKS9, a recombinant cytokine generated by conjugating an M cell-targeting peptide (CKS9) with c-terminus of the murine interleukin 6 (IL-6), which facilitated enhancement of mucosal immune response. Lactococcus lactis IL1403, a food-grade strain of lactic acid bacteria (LAB) which is widely used in dairy industry, was used as a host cell to express and secrete the IL-6-CKS9 for a mucosal vaccine adjuvant. The recombinant L. lactis IL1403 secreting IL-6-CKS9 was orally administered with a model antigen protein, M-BmpB (Brachyspira membrane protein B conjugated with CKS9), to BALB/c mice for mucosal immunization. ELISA analyses showed consistent enhancement tendencies in induction of anti-M-BmpB antibody levels both with mucosal (IgA) and systemic (IgG) immune responses in IL-6-CKS9-LAB treated group compared with other groups tested by conducting two separated mice immunization assays. In addition, we characterized that the oral administration of model protein antigen with live LAB producing IL-6-CKS9 could induce both Th1 and Th2 type immune responses by analysis of the specific anti-BmpB IgG1 and IgG2a isotypes in the sera and also investigated possible oral tolerance in our vaccine strategy. Collectively, our results showed successful production and secretion of recombinant murine IL-6 with M cell-targeting moiety (IL-6-CKS9) from L. lactis IL1403 and demonstrated the live recombinant LAB producing IL-6-CKS9 could have a potential to be used as an efficient adjuvant for peroral vaccination.
Volume 33(16)
Pages 1959-67
Published 2015-4-15
DOI 10.1016/j.vaccine.2015.02.061
PII S0264-410X(15)00250-9
PMID 25738814
MeSH Adjuvants, Immunologic* Administration, Oral Animals Female Gene Expression Gene Order Genetic Vectors Immune Tolerance Immunity, Mucosal* Immunization Interleukin-6 / genetics Interleukin-6 / immunology* Intestinal Mucosa / immunology Lactococcus lactis / genetics Lactococcus lactis / immunology* Lactococcus lactis / metabolism Mice Peptides / genetics Peptides / immunology* Peyer's Patches / immunology Recombinant Fusion Proteins / administration & dosage Recombinant Fusion Proteins / biosynthesis Recombinant Fusion Proteins / immunology*
IF 3.285
Times Cited 6
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL IMMUNOLOGY
Resource
Human and Animal Cells