Isolation and Characterization of Anti-SLP Single Domain Antibodies for the Therapy of C. difficile Infection

FieldValue
dc.contributor.authorKandalaft, Hiba
dc.date.accessioned2012-01-23T14:51:21Z
dc.date.available2013-01-28T20:49:18Z
dc.date.created2012
dc.date.issued2012
dc.identifier.urihttp://hdl.handle.net/10393/20624
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-6424
dc.description.abstractClostridium difficile is the leading cause of death from gastrointestinal infections in Canada. Current antiobiotic treatment is non-ideal due to the high incidence of relapse and the rise in hyper-virulent antibiotic-resistant strains. Surface layer proteins (SLPs) cover the entire bacterial surface and mediate adherence to host cells. Passive and active immunization against SLPs greatly enhances survival in hamsters, suggesting that antibody-mediated bacterial neutralization may be an effective alternative therapeutic strategy. Using a recombinant-antibody phage display library, and SLPs from strain QCD 32g58 as bait antigen, we isolated and extensively characterized 11 SLP-specific recombinant single-domain antibodies (sdAbs), in terms of affinity and specificity, intrinsic stability, and ability to inhibit cell motility. Several sdAbs exhibit promising characteristics for a potential oral therapeutic based on their high affinity, high thermal stability, and resistance to pepsin digestion. Our study provides the basis of a proof-of-principle model with which to develop specific, broadly neutralizing and intrinsically stable antibodies for the oral therapy of C. difficile infections, as an alternative to conventional antibiotic treatment.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectsdAb
dc.subjectsingle domain antibodies
dc.subjectC. difficile
dc.subjectmotility
dc.subjectprotease resistance
dc.subjectthermostability
dc.subjectantibody engineering
dc.subjectVH
dc.subjectVHH
dc.subjectcamelid
dc.subjectoral therapy of C. difficile infections
dc.titleIsolation and Characterization of Anti-SLP Single Domain Antibodies for the Therapy of C. difficile Infection
dc.typeThesis
dc.faculty.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
dc.contributor.supervisorTanha, Jamshid
dc.embargo.terms1 year
dc.degree.nameMSc
dc.degree.levelmasters
dc.degree.disciplineMédecine / Medicine
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
CollectionThèses, 2011 - // Theses, 2011 -

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