Adjuvant effect of bacterial outer membrane vesicles with penta-acylated lipopolysaccharide on antigen-specific T cell priming

作者:Lee Dong Ho; Kim Sang Hyun; Kang Wonseok; Choi Yoon Seok; Lee Sang Ho; Lee Sang Rae; You Sooseong; Lee Heung Kyu; Chang Kyu Tae*; Shin Eui Cheol
来源:Vaccine, 2011, 29(46): 8293-8301.
DOI:10.1016/j.vaccine.2011.08.102

摘要

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 Delta msbB/Delta pagP 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.

  • 出版日期2011-10-26