From In silico Protein Epitope Density Prediction to Testing Escherichia coli O157:H7 Vaccine Candidates in a Murine Model of Colonization.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a leading cause of foodborne illnesses worldwide and is a common serotype linked to hemorrhagic colitis and an important cause of hemolytic uremic syndrome (HUS). Treatment of EHEC O157:H7 infections is complicated, as antibiotics can exacerbate Shiga toxin (Stx) production and lead to more severe symptoms including HUS. To date, no vaccines have been approved for human use, exposing a void in both treatment and prevention of EHEC O157:H7 infections. Previously, our lab has shown success in identifying novel vaccine candidates via bio- and immunoinformatics approaches, which are capable of reducing bacterial colonization in an in vivo model of intestinal colonization. In this study, we further characterized 17 of the identified vaccine candidates at the bioinformatics level and evaluated the protective capacity of the top three candidates when administered as DNA vaccines in our murine model of EHEC O157:H7 colonization. Based on further immunoinformatic predictions, these vaccine candidates were expected to induce neutralizing antibodies in a Th2-skewed immunological response. Immunization of BALB/c mice with two of these candidates resulted in reduced bacterial colonization following EHEC O157:H7 challenge. Additionally, immune sera was shown to prevent bacterial adhesion in vitro to Caco-2 cells. Together, this study provides further validation of our immunoinformatic analyses and identifies promising vaccine candidates against EHEC O157:H7.
Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
Daniel
D
Tapia
Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
Brittany N
BN
Ross
Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
Anjana
A
Kalita
Department of Internal Medicine, University of Texas Medical Branch Galveston, TX, USA.
Mridul
M
Kalita
Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
Christopher L
CL
Hatcher
Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Translational Sciences, University of Texas Medical BranchGalveston, TX, USA.
Laura A
LA
Muruato
Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Translational Sciences, University of Texas Medical BranchGalveston, TX, USA; Department of Pathology and Sealy Center for Vaccine Development University of Texas Medical BranchGalveston, TX, USA.
Alfredo G
AG
Torres
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001422:Bacterial Adhesion / Q000187:drug effects; D018938:Caco-2 Cells; D019295:Computational Biology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control*; D019453:Escherichia coli O157 / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D000939:Epitopes; D022361:Escherichia coli Vaccines; D019444:Vaccines, DNA
Escherichia coli O157:H7; bioinformatics; immunoinformatics; type III secretion system; vaccine