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- Title
LOS oligosaccharide modification enhances dendritic cell responses to meningococcal native outer membrane vesicles expressing a non-toxic lipid A.
- Authors
Jones, Hannah E.; Copland, Alastair; Hamstra, Hendrik Jan; Cohen, Jonathan; Brown, Jeremy; Klein, Nigel; Ley, Peter; Dixon, Garth
- Abstract
Outer membrane vesicles ( OMV) are released by many bacteria, and contain immunogenic antigens in addition to harmful inflammatory factors, like lipopolysaccharides. Chemically detoxified OMV have been used in vaccines against N eisseria meningitidis ( Nm); however, little is known about their interaction with antigen presenting cells. In this study, we investigated the interaction of Nm OMV with human dendritic cells ( DC) to gain further understanding of their biological activity. We engineered a novel serogroup B Nm that is unencapsulated ( siaD), expresses pentacylated lipid A ( lpxL1), hence conferring reduced toxicity, and expresses an lgtB oligosaccharide structure designed to target OMV to DC via DC- SIGN. We show that the lgtB moiety is critical for internalization of NOMV by DC. Furthermore, the lgtB moiety significantly enhances DC maturation, IL-10 and IL-23 production in the presence of a pentacylated lipid A. While different DC phenotypes were observed for each NOMV, this had little effect on Th1 and Th2 cell differentiation; however, lgtBsignificantly increased Th17 cell expansion in the presence of pentacylated lipid A. We believe that lpxL1 / lgtB NOMV should be considered further as a vaccine vector, particularly considering the importance of lgtB in antigen uptake and further human studies on antigen-specific responses should be considered.
- Subjects
OLIGOSACCHARIDES; DENDRITIC cells; LIPOPOLYSACCHARIDES; NEISSERIA meningitidis; MENINGOCOCCAL vaccines; ANTIGEN presenting cells; VACCINATION; PHYSIOLOGY
- Publication
Cellular Microbiology, 2014, Vol 16, Issue 4, p519
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/cmi.12231