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 language | English |
---|---|
Pages (from-to) | 8293-8301 |
Number of pages | 9 |
Journal | Vaccine |
Volume | 29 |
Issue number | 46 |
DOIs | |
Publication status | Published - 2011 Oct 26 |
Bibliographical note
Funding Information:This study was supported by the Research Program for New Drug Target Discovery through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) ( 2010-0020471 ), the Basic Science Research Program through NRF funded by MEST ( 2010-0004539 ), the Korea Research Foundation Grant funded by the Korea Government ( KRF-2008-313-E00245 ), and the grant from KRIBB Research Initiative Program ( KBM4311022 ).
Keywords
- Adjuvant
- Outer membrane vesicles
- Penta-acylated LPS
- T cells
ASJC Scopus subject areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases