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

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• 作者：Dong Ho  ; Lee^a ;   ; ^b ;   ; ¹ ; Sang-Hyun  ; Kim^c ;   ; ¹ ; Wonseok  ; Kang^a ;   ; ¹ ; Yoon Seok  ; Choi^a ; Sang-Ho  ; Lee^c ; Sang-Rae  ; Lee^c ; Sooseong  ; You^a ; Heung Kyu  ; Lee^d ; Kyu-Tae  ; Chang^c ;   ; ^{changkt@kribb.re.kr} ; Eui-Cheol  ; Shin^a ;   ; ^{ecshin@kaist.ac.kr}
• 关键词：Adjuvant ; Outer membrane vesicles ; Penta-acylated LPS ; T cells
• 刊名：Vaccine
• 出版年：2011
• 出版时间：26 October 2011
• 年：2011
• 卷：29
• 期：46
• 页码：8293-8301
• 全文大小：1114 K

文摘

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 ¦¤msbB/¦¤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.