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Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2018.00132

Immunization with Skp Delivered on Outer Membrane Vesicles Protects Mice against Enterotoxigenic Escherichia coli Challenge

 Michael P. Hays1,  Diane Houben2, Yang Yang1, Joen Luirink2, 3 and  Philip R. Hardwidge1*
  • 1Kansas State University, United States
  • 2VU University Amsterdam, Netherlands
  • 3Abera Bioscience (Sweden), Sweden

Outer membrane vesicles (OMVs) are promising vaccine components because they combine antigen and adjuvant in a single formulation. Detoxified Salmonella enterica strains that express penta-acylated lipid A retain OMV immunogenicity but with reduced reactogenicity. We have previously shown that a recombinant form of the enterotoxigenic Escherichia coli (ETEC) seventeen kilodalton protein (Skp) protects mice in a pulmonary challenge model, when fused to the glutathione-S-transferase (GST) epitope and combined with cholera toxin. Here we compared directly the efficacy of expressing Skp in detoxified Salmonella OMVs to GST-Skp for their ability to protect mice against ETEC challenge. We observed that the display of Skp on OMVs, in the absence of exogenous adjuvant, protects the mice as well as the recombinant GST-Skp with adjuvant, showing that we can achieve protection when antigen and adjuvant are administered as a single formulation. Collectively, these data demonstrate the utility of using OMVs for the expression and display of antigens for use in vaccine development and validate previously published work demonstrating that immunization with Skp is efficacious in protecting mice against ETEC challenge.

Keywords: Enterotoxigenic Escherichia coli, Vaccines, outer membrane vesicles, mouse models, Infection

Received: 17 Jan 2018; Accepted: 13 Apr 2018.

Edited by:

Chad J. Roy, Tulane University School of Medicine, United States

Reviewed by:

Ariadnna Cruz-Córdova, Hospital Infantil de México Federico Gómez, Mexico
Susan M. Bueno, Pontificia Universidad Católica de Chile, Chile  

Copyright: © 2018 Hays, Houben, Yang, Luirink and Hardwidge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Philip R. Hardwidge, Kansas State University, Manhattan, KS, United States,