Abstract
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) 17 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.
Highlights
Enterotoxigenic Escherichia coli (ETEC) strains are important bacterial pathogens of both humans and livestock (Fleckenstein et al, 2010)
The lack of a successful, licensed ETEC vaccine is attributed to a number of general limiting factors and challenges that hamper the development of vaccine candidates and their downstream implementation
The variability among strains of relevance to human health makes the development of vaccines with sufficient coverage of ETEC strains extremely challenging and increases the likelihood that vaccine candidates will fail at later stages of development
Summary
Enterotoxigenic Escherichia coli (ETEC) strains are important bacterial pathogens of both humans and livestock (Fleckenstein et al, 2010). Vaccination with Skp-GST protected mice from an otherwise lethal dose of ETEC, reduced ETEC burdens in the lungs, and enhanced IgA responses (Kumar et al, 2015; Hays et al, 2016).
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