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In vivo persistence and protective efficacy of the Bacille Calmette Guérin vaccine overexpressing the HspX latency antigen

Joanne Spratt, Warwick J. Britton and James A. Triccas

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New strategies to control infection with Mycobacterium tuberculosis, the causative agent of
tuberculosis, are urgently required, particularly in areas where acquired immune
immunodeficiences are prevalent. In this report we have determined if modification of the
current tuberculosis vaccine, Mycobacterium bovis BCG, to constitutively express the
mycobacterial HspX latency antigen altered its protective effect against challenge with
virulent M. tuberculosis. Overexpression of M. tuberculosis HspX in BCG caused reduced
growth in aerated cultures compared to control BCG, but growth under limited oxygen
availability was not markedly altered. Upon infection of mice, BCG:HspX displayed tissue-
specific attenuation compared to control BCG, with reduced growth within the lung and liver
but not the spleen. Both BCG:HspX and control BCG protected mice against aerosol M.
tuberculosis challenge to a similar extent, however, immunodeficient mice infected with
BCG:HspX survived significantly longer than mice infected with the control BCG strain.
Therefore, altering the in vivo persistence of BCG by overexpression of HspX may be one
important step towards developing a new tuberculosis vaccine with an improved safety profile
and suitable protective efficacy against M. tuberculosis infection.

Authors

Joanne Spratt

Centenary Institute of Cancer Medicine and Cell Biology, Discipline of Infectious Diseases and Immunology, University of Sydney, Australia

Warwick J. Britton

Centenary Institute of Cancer Medicine and Cell Biology; Discipline of Medicine and Discipline of Infectious Diseases and Immunology, University of Sydney, Australia

James A. Triccas Corresponding author: j.triccas@usyd.edu.au

Centenary Institute of Cancer Medicine and Cell Biology; Microbial Pathogenesis and Immunity Group, Discipline of Infectious Diseases and Immunology, University of Sydney, Australia

This is an open-access article

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.