Towards a vaccine for chronic obstructive pulmonary disease

Authors

  • R. L. Clancy

    Corresponding author
    1. Department of Immunology, Hunter Area Pathology Service and Hunter Immunology Limited, Newcastle, New South Wales, Australia
    • Robert L. Clancy, Hunter Immunology Ltd., Level 4, DMCSB (David Maddison Building), University of Newcastle, Callaghan, NSW 2308, Australia. Email: robert.clancy@newcastle.edu.au

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  • Funding: None.

  • Conflict of interest: E/Professor Robert Clancy is a consultant for Hunter Immunology Limited, the company working on the oral vaccine discussed in this review. He owns shares/stock in this company.

  • In this review, Robert Clancy summarises 30 years of work in mucosal immunology. The review does not include any original data that is not in the public record.

Abstract

This review discusses chronic obstructive pulmonary disease as an outcome of two pathogenic pathways: the first resulting from inhalation of toxins and the second a consequence of bacterial colonisation of damaged airways. Earlier assessment of the role played by bacteria in acute exacerbations was compromised by a deficiency of quality data and the use of parameters more relevant to invasive infection. Data are reviewed to support a hypothesis that states intrabronchial inflammation reflects an excessive and inappropriate host response (largely mediated by Th17 cells derived from gut-associated lymphoid tissues) to colonising bacteria acting as an ‘antigen sump’ (in essence, a hypersensitivity reaction). It is proposed that both viral and bacterial infections exacerbate inflammation through a common pathway that involves colonising bacteria. An oral vaccine containing inactivated non-typeable Haemophilus influenzae augments a protective loop that involves the aspiration of bronchus content into the gut and reduces the severity of acute exacerbations including the need for hospital admission by reducing the ‘load’ of bacteria comprising this final common path. The positive clinical results from trials using oral NTHi support both the concept that bacterial colonisation of damaged airways is a potent second pathogenic pathway and that oral immunotherapy provides a significant therapeutic advance in limiting damage in chronic obstructive pulmonary disease.

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