title: Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens.
abstract: Naturally acquired immunity against invasive pneumococcal disease (IPD) is thought to be dependent on anti-capsular antibody. However nasopharyngeal colonisation by Streptococcus pneumoniae also induces antibody to protein antigens that could be protective. We have used human intravenous immunoglobulin preparation (IVIG), representing natural IgG responses to S. pneumoniae, to identify the classes of antigens that are functionally relevant for immunity to IPD. IgG in IVIG recognised capsular antigen and multiple S. pneumoniae protein antigens, with highly conserved patterns between different geographical sources of pooled human IgG. Incubation of S. pneumoniae in IVIG resulted in IgG binding to the bacteria, formation of bacterial aggregates, and enhanced phagocytosis even for unencapsulated S. pneumoniae strains, demonstrating the capsule was unlikely to be the dominant protective antigen. IgG binding to S. pneumoniae incubated in IVIG was reduced after partial chemical or genetic removal of bacterial surface proteins, and increased against a Streptococcus mitis strain expressing the S. pneumoniae protein PspC. In contrast, depletion of type-specific capsular antibody from IVIG did not affect IgG binding, opsonophagocytosis, or protection by passive vaccination against IPD in murine models. These results demonstrate that naturally acquired protection against IPD largely depends on antibody to protein antigens rather than the capsule.
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.affiliation: Infectious Diseases & Microbiology Unit, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Reglinski
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Jose
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
authors.forename: Win Yan
authors.identifier: 0000-0001-6964-5091
authors.initials: WY
authors.lastname: Chan
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
authors.forename: Helina
authors.initials: H
authors.lastname: Marshall
authors.affiliation: Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Corné
authors.initials: C
authors.lastname: de Vogel
authors.affiliation: Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Institute of Child Health, University College London, London, United Kingdom.
authors.forename: David
authors.identifier: 0000-0002-0769-5242
authors.initials: D
authors.lastname: Goldblatt
authors.affiliation: Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Petersen
authors.affiliation: Clinical Immunology Department, Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Baxendale
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
authors.forename: Jeremy S
authors.identifier: 0000-0002-5650-5361
authors.initials: JS
authors.lastname: Brown
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D008565:Membrane Proteins