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Original article
Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease
  1. Alison N Thorburn1,
  2. Brendan J O'Sullivan2,
  3. Ranjeny Thomas2,
  4. Rakesh K Kumar3,
  5. Paul S Foster1,
  6. Peter G Gibson1,4,
  7. Philip M Hansbro1
  1. 1Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia
  2. 2University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  3. 3Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
  4. 4Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, New South Wales, Australia
  1. Correspondence to Associate Professor Philip Hansbro, Level 3, David Maddison Clinical Sciences Building, Cnr King & Watt Sts, Newcastle, New South Wales, 2300, Australia; philip.hansbro{at}newcastle.edu.au

Abstract

Background Infections with some bacteria, including Streptococcus pneumoniae, have been associated with a reduced incidence of asthma. Components of S pneumoniae may have the potential to modulate allergic inflammatory responses and suppress the development of asthma.

Objectives To determine if human S pneumoniae vaccines have the potential to suppress asthma by elucidating their effect on allergic airways disease (AAD) in mouse models.

Methods AAD was induced in BALB/c mice by intraperitoneal sensitisation and intranasal challenge with ovalbumin. Pneumococcal conjugate or polysaccharide vaccines were administered at the time of sensitisation or during established AAD. Hallmark features of AAD were assessed. Levels of regulatory T cells (Tregs) were quantified by fluorescence-activated cell sorting, and their immunoregulatory capacity was assessed using proliferation assays and anti-CD25 antibody treatment.

Results Intranasal administration of the conjugate vaccine, but not the polysaccharide vaccine, suppressed the hallmark features of AAD, including: eosinophilic and T helper 2-mediated inflammation; airway hyper-responsiveness; circulating immunoglobulin E (IgE) levels; and mucus hypersecretion. Intramuscular administration of the conjugate vaccine had limited protective effects. The conjugate vaccine increased Tregs in the lung-draining lymph nodes, lung and spleen. Furthermore, conjugate vaccine-induced Tregs had an enhanced capacity to suppress T effector responses. Anti-CD25 administration reversed the suppressive effects of the conjugate vaccine.

Conclusions A currently available human conjugate vaccine suppresses the hallmark features of AAD through the induction of Tregs. Thus targeted administration may provide a novel immunoregulatory treatment for asthma.

  • Asthma
  • Streptococcus pneumoniae
  • regulatory T cells
  • immunoregulatory therapy
  • allergic lung disease
  • asthma mechanisms
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Footnotes

  • Funding The Hill family, Asthma Foundation NSW, CRC for Asthma and Airways, National Health and Medical Research Council (project grants 401238, 569219) and The University of Newcastle.

  • Competing interests None.

  • Ethics approval All experiments were approved by the Animal Care and Ethics Committee, University of Newcastle.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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