title: Efficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogens.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Tanweer S
authors.initials: TS
authors.lastname: Zaidi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Cagla
authors.initials: C
authors.lastname: Bozkurt-Guzel
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Tauqeer H
authors.initials: TH
authors.lastname: Zaidi
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Lederer
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States 3Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, United States.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Priebe
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
mesh_terms: D000117:Acetylglucosamine / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D003315:Cornea / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015821:Eye Infections, Fungal / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007634:Keratitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine