Show simple item record

dc.contributor.authorBerry, Sophia
dc.contributor.authorRust, Steven
dc.contributor.authorCaceres, Carolina
dc.contributor.authorIrving, Lorraine
dc.contributor.authorBartholdson Scott, Josefin
dc.contributor.authorTabor, David E
dc.contributor.authorDougan, Gordon
dc.contributor.authorChristie, Graham
dc.contributor.authorWarrener, Paul
dc.contributor.authorMinter, Ralph
dc.contributor.authorGrant, Andrew
dc.date.accessioned2021-11-16T00:30:15Z
dc.date.available2021-11-16T00:30:15Z
dc.date.issued2022-01
dc.identifier.issn1942-0862
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330649
dc.description.abstractThe increasing global occurrence of recalcitrant multi-drug resistant Klebsiella pneumoniae infections warrants the investigation of alternative therapy options, such as the use of monoclonal antibodies (mAbs). We used a target-agnostic phage display approach to K. pneumoniae bacteria lacking bulky, highly variable surface polysaccharides in order to isolate antibodies targeting conserved epitopes among clinically relevant strains. One antibody population contained a high proportion of unique carbohydrate binders, and biolayer interferometry revealed these antibodies bound to lipopolysaccharide (LPS). Antibodies that bound to O1 and O1/O2 LPS were identified. Antibodies were found to promote opsonophagocytic killing by human monocyte-derived macrophages and clearance of macrophage-associated bacteria when assessed using high-content imaging. One antibody, B39, was found to protect mice in a lethal model of K. pneumoniae pneumonia against both O1 and O2 strains when dosed therapeutically. High-content imaging, western blotting and fluorescence-activated cell sorting were used to determine binding to a collection of clinical K. pneumoniae O1 and O2 strains. The data suggests B39 binds to D-galactan-I and D-galactan-II of the LPS of O1 and O2 strains. Thus, we have discovered an mAb with novel binding and functional activity properties that is a promising candidate for development as a novel biotherapeutic for the treatment and prevention of K. pneumoniae infections.
dc.description.sponsorshipThis work was funded by AstraZeneca (MedImmune PhD) and the Cambridge Biomedical Research Centre.
dc.publisherInforma UK Limited
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titlePhenotypic whole-cell screening identifies a protective carbohydrate epitope on Klebsiella pneumoniae.
dc.typeArticle
prism.publicationNameMAbs
dc.identifier.doi10.17863/CAM.78094
dcterms.dateAccepted2021-11-10
rioxxterms.versionofrecord10.1080/19420862.2021.2006123
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-11-10
dc.contributor.orcidBerry, Sophia [0000-0002-2184-1074]
dc.contributor.orcidDougan, Gordon [0000-0003-0022-965X]
dc.contributor.orcidChristie, Graham [0000-0001-7177-9646]
dc.contributor.orcidGrant, Andrew [0000-0001-9746-2989]
dc.identifier.eissn1942-0870
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-12-20
datacite.issupplementedby.urlhttps://doi.org/10.17863/CAM.78423
cam.orpheus.successTue Feb 01 19:02:15 GMT 2022 - Embargo updated*
cam.orpheus.counter1
rioxxterms.freetoread.startdate2021-12-20


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record