Naturally acquired human immunity to pneumococcus is dependent on antibody to protein antigens

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Wilson, Robert and Cohen, Jonathan M. and Reglinski, Mark and Jose, Ricardo J. and Chan, Win Yan and Marshall, Helina and de Vogel, Corné and Gordon, Stephen and Goldblatt, David and Petersen, Fernanda C. and Baxendale, Helen and Brown, Jeremy S. (2017) Naturally acquired human immunity to pneumococcus is dependent on antibody to protein antigens. PLOS Pathogens, 13 (1). e1006137. ISSN 1553-7366 (https://doi.org/10.1371/journal.ppat.1006137)

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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.

ORCID iDs

Wilson, Robert, Cohen, Jonathan M., Reglinski, Mark, Jose, Ricardo J., Chan, Win Yan, Marshall, Helina ORCID logoORCID: https://orcid.org/0000-0001-5054-7301, de Vogel, Corné, Gordon, Stephen, Goldblatt, David, Petersen, Fernanda C., Baxendale, Helen and Brown, Jeremy S.;
  • Item type:Article
    ID code:83984
    Dates:
    Date
    Event
    30 January 2017
    Published
    17 December 2016
    Accepted
    Notes:Funding Information: This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health?s NIHR Biomedical Research Centre?s funding scheme. RW was supported by a UCL Impact PhD Fellowship. JMC was supported by a NIHR Academic Clinical Lectureship and received funding from the Academy of Medical Sciences. RJJ, WYC, and HM were respectively supported by PhD fellowships from the Wellcome Trust, MRC, and BBSRC. MR was supported by a Meningitis NOW project grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2017 Wilson et al. Wilson R, Cohen JM, Reglinski M, Jose RJ, Chan WY, Marshall H, et al. (2017) Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens. PLoS Pathog 13(1): e1006137. https://doi.org/10.1371/journal.ppat.1006137 Correction: 8 Mar 2017: Wilson R, Cohen JM, Reglinski M, Jose RJ, Chan WY, et al. (2017) Correction: Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens. PLOS Pathogens 13(3): e1006259. https://doi.org/10.1371/journal.ppat.1006259
    Subjects:Science > Microbiology
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:02 Feb 2023 10:52
    Last modified:15 Dec 2024 10:20
    URI:https://strathprints.strath.ac.uk/id/eprint/83984
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