Show simple item record

dc.contributor.authorZhao, Geen_US
dc.contributor.authorZaidi, Tanweer S.en_US
dc.contributor.authorBozkurt-Guzel, Caglaen_US
dc.contributor.authorZaidi, Tauqeer H.en_US
dc.contributor.authorLederer, James A.en_US
dc.contributor.authorPriebe, Gregory P.en_US
dc.contributor.authorPier, Gerald B.en_US
dc.date.accessioned2017-02-18T01:58:51Z
dc.date.issued2016en_US
dc.identifier.citationZhao, Ge, Tanweer S. Zaidi, Cagla Bozkurt-Guzel, Tauqeer H. Zaidi, James A. Lederer, Gregory P. Priebe, and Gerald B. Pier. 2016. “Efficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogens.” Investigative Ophthalmology & Visual Science 57 (15): 6797-6804. doi:10.1167/iovs.16-20358. http://dx.doi.org/10.1167/iovs.16-20358.en
dc.identifier.issn0146-0404en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:30371091
dc.description.abstractPurpose Developing immunotherapies for fungal eye infections is a high priority. We analyzed fungal pathogens for expression of the surface polysaccharide, poly-N-acetyl glucosamine (PNAG), and used a mouse model of ocular keratitis caused by Aspergillus flavus, A. fumigatus, or Fusarium solani to determine if PNAG was an immunotherapy target and requirements for ancillary cellular and molecular immune effectors. Methods: Enzyme-linked immunosorbent assay (ELISA) or immunofluorescence was used to detect PNAG on fungal cells. Keratitis was induced by scratching corneas of C57BL/6, IL-17R KO, RAG-1 KO, or IL-22 KO mice followed by inoculation with fungal pathogens. Goat antibodies to PNAG, a PNAG-specific human IgG1 monoclonal antibody, or control antibodies were injected either prophylactically plus therapeutically or therapeutically only, and corneal pathology and fungal levels determined in infected eyes at 24 or 48 hours after infection. Results: All tested fungal species produced PNAG. Prophylactic or therapeutic treatment by intraperitoneal (IP) injection of antibody to PNAG combined with post-infection topical application of antibody, the latter also used for A. fumigatus, led to reduced fungal levels, corneal pathology, and cytokine expression. Topical administration only of the PNAG monoclonal antibodies (MAb) reduced fungal loads and corneal pathology. There was no antibody protection in IL-17R KO, RAG-1 KO, or IL-22 KO mice. Conclusions: Poly-N-acetyl glucosamine is produced by clinically important fungal ocular pathogens. Antibody to PNAG demonstrated protection against Aspergillus and Fusarium keratitis, requiring T cells producing IL-17 and IL-22. These findings indicate the potential to prevent or treat fungal infections by vaccines and immunotherapeutics to PNAG.en
dc.language.isoen_USen
dc.publisherThe Association for Research in Vision and Ophthalmologyen
dc.relation.isversionofdoi:10.1167/iovs.16-20358en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215555/pdf/en
dash.licenseLAAen_US
dc.subjectfungal keratitisen
dc.subjectPNAGen
dc.subjectvaccineen
dc.subjectMAben
dc.subjectimmunotherapyen
dc.titleEfficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogensen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalInvestigative Ophthalmology & Visual Scienceen
dash.depositing.authorLederer, James A.en_US
dc.date.available2017-02-18T01:58:51Z
dc.identifier.doi10.1167/iovs.16-20358*
dash.authorsorderedfalse
dash.contributor.affiliatedPriebe, Gregory
dash.contributor.affiliatedPier, Gerald
dash.contributor.affiliatedLederer, James


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record