title: Population variation in anti-S. aureus IgG isotypes influences surface protein A mediated immune subversion.
abstract: BACKGROUND
  Staphylococcus aureus is a pathogen which causes life-threatening infection, the incidence of which rises during adult life. This, together with the emergence of drug-resistant strains and the expansion of more susceptible elderly populations, represents the rationale for the ongoing development of S. aureus vaccines targeting adult populations. Humoral responses to S. aureus naturally develop early in life, influence susceptibility to infection, and potentially influence the effect of vaccination. Despite this, the nature of pre-existing anti-S. aureus antibodies in healthy adult populations is not fully characterised.
  
  
  METHODS
  Immunoglobulin levels against S. aureus surface antigens were measured by a filter membrane enzyme-linked immunosorbent assay using fixed ΔSpA S. aureus as an antigen in serum samples obtained from three clinical cohorts comprising 133 healthy adult volunteers from 19 to 65 years of age. Functional capacity of antibody was also assessed, using antibody-mediated attachment of FITC-stained S. aureus to differentiated HL-60 cells.
  
  
  RESULTS
  Wide variation in the concentrations of immunoglobulins recognising S. aureus surface antigens was observed among individuals in all three cohorts. There was a decline of anti-S. aureus IgG1 with age, and a similar trend was observed in IgM, but not in IgA or other IgG sub-classes. Antibody mediated bacterial attachment to cells was associated with IgG1 and IgG3 concentrations in serum. The presence of SpA on the bacterial cell surface reduced antibody-mediated binding of bacteria to phagocytes in serum with low, but not high, levels of naturally occurring anti-S. aureus IgG3 antibodies.
  
  
  CONCLUSIONS
  Naturally acquired immunoglobulin responses to S. aureus are heterogeneous in populations and their concentrations alter during adulthood. Elevated IgG1 or IgG3 titres against S. aureus enhance S. aureus recognition by phagocytosis and may be correlates of natural protection and/or vaccine efficacy in adult populations.
authors.affiliation: Jenner Institute, Centre for Cellular & Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Whitehouse
authors.affiliation: Jenner Institute, Centre for Cellular & Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: Flaxman
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Drive, Oxford OX3 7LE, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Rollier
authors.affiliation: Jenner Institute, Centre for Cellular & Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom; Department of Academic Medicine, Royal Centre for Defence Medicine, Birmingham B15 2SQ, United Kingdom.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: O'Shea
authors.affiliation: Environmental Medicine and Science Division, Institute of Naval Medicine, Hampshire PO12 2DL, United Kingdom.
authors.forename: Joanne
authors.initials: J
authors.lastname: Fallowfield
authors.affiliation: Environmental Medicine and Science Division, Institute of Naval Medicine, Hampshire PO12 2DL, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Lindsay
authors.affiliation: Environmental Medicine and Science Division, Institute of Naval Medicine, Hampshire PO12 2DL, United Kingdom.
authors.forename: Frances
authors.initials: F
authors.lastname: Gunner
authors.affiliation: Nuffield Department of Primary Care Health Sciences, New Radcliffe House, 2nd floor, Walton Street, Jericho OX2 6NW, United Kingdom.
authors.forename: Kyle
authors.initials: K
authors.lastname: Knox
authors.affiliation: Jenner Institute, Centre for Cellular & Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom; Nuffield Department of Medicine, Department of Microbiology, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. Electronic address: david.wyllie@ndm.ox.ac.uk.
authors.forename: David H
authors.initials: DH
authors.lastname: Wyllie
authors.affiliation: Jenner Institute, Centre for Cellular & Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018922:HL-60 Cells; D064368:Healthy Volunteers; D006801:Humans; D057131:Immune Evasion; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D016036:Seroepidemiologic Studies; D013211:Staphylococcus aureus / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G
keywords: Antibody; Immunosenescence; Protein A; Staphylococcus aureus; Vaccine