A combined vaccine approach against Vibrio cholerae and ETEC based on outer membrane vesicles

作者：Leitner Deborah R; Lichtenegger Sabine; Temel Philipp; Zingl Franz G; Ratzberger Desiree; Roier Sandro; Schild Pruefert Kristina; Feichter Sandra; Reidl Joachim; Schild Stefan^*

来源：Frontiers in Microbiology, 2015, 6: 823.

DOI：10.3389/fmicb.7015.00823

• outer membrane vesicles
• Vibrio cholerae
• enterotoxigenic Escherichia coli
• vaccines
• enteric pathogens
• combined vaccine

Enteric infections induced by pathogens like Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) remain a massive burden in developing countries with increasing morbidity and mortality rates. Previously, we showed that the immunization with genetically detoxified outer membrane vesicles (OMVs) derived from V cholerae elicits a protective immune response based on the generation of 0 antigen antibodies, which effectively block the motility by binding to the sheathed flagellum. In this study, we investigated the potential of lipopolysaccharide (LPS)-modified and toxin negative OMVs isolated from V cholerae and ETEC as a combined OMV vaccine candidate. Our results indicate that the immunization with V cholerae or ETEC OMVs induced a species-specific immune response, whereas the combination of both OMV species resulted in a high-titer, protective immune response against both pathogens. Interestingly, the immunization with V cholerae OMVs alone resulted in a so far uncharacterized and cholera toxin B-subunit (CTB) independent protection mechanism against an ETEC colonization. Furthermore, we investigated the potential use of V cholerae OMVs as delivery vehicles for the heterologously expression of the ETEC surface antigens, CFA/I, and FliC. Although we induced a detectable immune response against both heterologously expressed antigens, none of these approaches resulted in an improved protection compared to a simple combination of V cholerae and ETEC OMVs. Finally, we expanded the current protection model from V cholerae to ETEC by demonstrating that the inhibition of motility via anti-FliC antibodies represents a relevant protection mechanism of an OMV-based ETEC vaccine candidate in vivo.

• 出版日期2015-8-11