title: The exceptionally broad-based potential of active and passive vaccination targeting the conserved microbial surface polysaccharide PNAG.
abstract: A challenging component of vaccine development is the large serologic diversity of protective antigens. Remarkably, there is a conserved surface/capsular polysaccharide, one of the most effective vaccine targets, expressed by a large number of bacterial, fungal and eukaryotic pathogens: poly-N-acetyl glucosamine (PNAG). Natural antibodies to PNAG are poorly effective at mediating in vitro microbial killing or in vivo protection. Removing most of the acetate substituents to produce a deacetylated glycoform, or using synthetic oligosaccharides of poly-β-1-6-linked glucosamine conjugated to carrier proteins, results in vaccines that elicit high levels of broad-based immunity. A fully human monoclonal antibody is highly active in laboratory and preclinical studies and has been successfully tested in a phase-I setting. Both the synthetic oligosaccharide conjugate vaccine and MAb will be further tested in humans starting in 2016; but, even if effective against only a fraction of the PNAG-producing pathogens, a major advance in vaccine-preventable diseases will occur.
authors.affiliation: a Division of Infectious Diseases, Department of Medicine , Brigham and Women's Hospital, Harvard Medical School , Boston , MA , USA.
authors.forename: David
authors.initials: D
authors.lastname: Skurnik
authors.affiliation: a Division of Infectious Diseases, Department of Medicine , Brigham and Women's Hospital, Harvard Medical School , Boston , MA , USA.
authors.forename: Colette
authors.initials: C
authors.lastname: Cywes-Bentley
authors.affiliation: a Division of Infectious Diseases, Department of Medicine , Brigham and Women's Hospital, Harvard Medical School , Boston , MA , USA.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
mesh_terms: D000117:Acetylglucosamine / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology* / Q000302:isolation & purification; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D005657:Fungal Vaccines / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D017780:Malaria Vaccines / Q000276:immunology* / Q000302:isolation & purification; D014611:Vaccination / Q000379:methods*
chemical_list: D001428:Bacterial Vaccines; D005657:Fungal Vaccines; D017780:Malaria Vaccines; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine
keywords: Ply-N-acetyl glucosamine; antibiotic-resistance; capsule; conjugate vaccine; monoclonal antibody