title: Adjuvant effect of bacterial outer membrane vesicles with penta-acylated lipopolysaccharide on antigen-specific T cell priming.
abstract: Outer membrane vesicles (OMV) are nano-sized spherical blebs shed by Gram-negative bacteria and have been utilized in vaccine development. In the present study, we evaluated T cell adjuvant activity of OMV with strictly penta-acylated LPS produced by ΔmsbB/ΔpagP mutant of non-pathogenic Escherichia coli W3110 (mOMV) compared to OMV with hexa-acylated LPS produced by wild-type E. coli W3110 (wOMV). Penta-acylation of LPS renders mOMV less endotoxic than wOMV in in vitro and in vivo toxicity assays. In mice, mOMV has adjuvant activity on T cell priming not only in KLH protein immunization but also in SIINFEKL peptide immunization. The T-cell adjuvant activity of mOMV was comparable to that of wOMV and LPS and was abrogated in TLR4 K/O mice. In innate immunity, mOMV stimulated BMDCs to up-regulate co-stimulatory and antigen-presenting molecules and to produce pro-inflammatory cytokines in a TLR4-dependent manner. Of note, mOMV induced cytokine production at a significantly less extent compared with wOMV. Taken together, we propose that mOMV with penta-acylated LPS is a safe vaccine adjuvant for T cell priming and can be used in vaccine development against viral diseases and cancer.
authors: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, 291 Daejeon, Republic of Korea
authors: Dong Ho
authors: DH
authors: Lee
authors: Sang-Hyun
authors: SH
authors: Kim
authors: Wonseok
authors: W
authors: Kang
authors: Yoon Seok
authors: YS
authors: Choi
authors: Sang-Ho
authors: SH
authors: Lee
authors: Sang-Rae
authors: SR
authors: Lee
authors: Sooseong
authors: S
authors: You
authors: Heung Kyu
authors: HK
authors: Lee
authors: Kyu-Tae
authors: KT
authors: Chang
authors: Eui-Cheol
authors: EC
authors: Shin
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005326:Fetal Proteins; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D020825:T-Box Domain Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D000098908:Brachyury Protein
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005326:Fetal Proteins; D008070:Lipopolysaccharides; D010455:Peptides; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein