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.
| Original language | English |
|---|---|
| Article number | 132 |
| Journal | Frontiers in Cellular and Infection Microbiology |
| Volume | 8 |
| Issue number | MAY |
| DOIs | |
| Publication status | Published - 1 May 2018 |
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Keywords
- Enterotoxigenic Escherichia coli
- Infection
- Mouse models
- Outer membrane vesicles
- Vaccines
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Immunization with Skp delivered on outer membrane vesicles protects mice against enterotoxigenic Escherichia coli CHALLENGE. / Hays, Michael P.; Houben, Diane; Yang, Yang; Luirink, Joen; Hardwidge, Philip R.
In: Frontiers in Cellular and Infection Microbiology, Vol. 8, No. MAY, 132, 01.05.2018.Research output: Contribution to Journal › Article › Academic › peer-review
TY - JOUR
T1 - Immunization with Skp delivered on outer membrane vesicles protects mice against enterotoxigenic Escherichia coli CHALLENGE
AU - Hays, Michael P.
AU - Houben, Diane
AU - Yang, Yang
AU - Luirink, Joen
AU - Hardwidge, Philip R.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - Enterotoxigenic Escherichia coli
KW - Infection
KW - Mouse models
KW - Outer membrane vesicles
KW - Vaccines
UR - http://www.scopus.com/inward/record.url?scp=85046848502&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046848502&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2018.00132
DO - 10.3389/fcimb.2018.00132
M3 - Article
VL - 8
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
SN - 2235-2988
IS - MAY
M1 - 132
ER -