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

Dong Ho Lee, Sang Hyun Kim, Wonseok Kang, Yoon Seok Choi, Sang Ho Lee, Sang Rae Lee, Sooseong You, Heung Kyu Lee, Kyu Tae Chang, Eui Cheol Shin

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

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 Δ msbB/Δ 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.

Original languageEnglish
Pages (from-to)8293-8301
Number of pages9
JournalVaccine
Volume29
Issue number46
DOIs
Publication statusPublished - 2011 Oct 26
Externally publishedYes

Keywords

  • Adjuvant
  • Outer membrane vesicles
  • Penta-acylated LPS
  • T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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