title: Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens.
abstract: Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Colette
authors.initials: C
authors.lastname: Cywes-Bentley
authors.forename: David
authors.initials: D
authors.lastname: Skurnik
authors.forename: Tanweer
authors.initials: T
authors.lastname: Zaidi
authors.forename: Damien
authors.initials: D
authors.lastname: Roux
authors.forename: Rosane B
authors.initials: RB
authors.lastname: Deoliveira
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Garrett
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.forename: Jennifer
authors.initials: J
authors.lastname: O'Malley
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kinzel
authors.forename: Tauqeer
authors.initials: T
authors.lastname: Zaidi
authors.forename: Astrid
authors.initials: A
authors.lastname: Rey
authors.forename: Christophe
authors.initials: C
authors.lastname: Perrin
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: Alexander K K
authors.initials: AK
authors.lastname: Kayatani
authors.forename: Tomas
authors.initials: T
authors.lastname: Maira-Litràn
authors.forename: Marina L
authors.initials: ML
authors.lastname: Gening
authors.forename: Yury E
authors.initials: YE
authors.lastname: Tsvetkov
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Bakaletz
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Pelton
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
mesh_terms: D000117:Acetylglucosamine / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D016667:Bacterial Capsules / Q000276:immunology / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D005658:Fungi / Q000276:immunology / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000276:immunology / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009181:Mycoses / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D009895:Opsonin Proteins / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D009895:Opsonin Proteins; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine
keywords: animal models; carbohydrates; immunotherapy; infectious diseases; malaria