HspX-mediated protection against tuberculosis depends on its chaperoning of a mycobacterial molecule

Taylor, Jennifer L., Wieczorek, Agatha, Keyser, Andrew R., Grover, Ajay, Flinkstrom, Rachel, Karls, Russell K., Bielefeldt-Ohmann, Helle, Dobos, Karen M. and Izzo, Angelo A. (2012) HspX-mediated protection against tuberculosis depends on its chaperoning of a mycobacterial molecule. Immunology and Cell Biology, 90 10: 945-954. doi:10.1038/icb.2012.34

Author Taylor, Jennifer L.
Wieczorek, Agatha
Keyser, Andrew R.
Grover, Ajay
Flinkstrom, Rachel
Karls, Russell K.
Bielefeldt-Ohmann, Helle
Dobos, Karen M.
Izzo, Angelo A.
Title HspX-mediated protection against tuberculosis depends on its chaperoning of a mycobacterial molecule
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
Publication date 2012-11
Sub-type Article (original research)
DOI 10.1038/icb.2012.34
Volume 90
Issue 10
Start page 945
End page 954
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2013
Language eng
Formatted abstract
New approaches consisting of 'multistage' vaccines against (TB) are emerging that combine early antigenic proteins with latency-associated antigens. In this study, HspX was tested for its potential to elicit both short- and long-term protective immune responses. HspX is a logical component in vaccine strategies targeting protective immune responses against primary infection, as well as against reactivation of latent infection, because as previously shown, it is produced during latency, and as our studies show, it elicits protection within 30 days of infection. Recent studies have shown that the current TB vaccine, bacilli Calmette-Guerin (BCG), does not induce strong interferon-γ T-cell responses to latency-associated antigens like HspX, which may be in part why BCG fails to protect against reactivation disease. We therefore tested HspX protein alone as a prophylactic vaccine and as a boost to BCG vaccination, and found that HspX purified from M. tuberculosis cell lysates protected mice against aerosol challenge and improved the protective efficacy of BCG when used as a booster vaccine. Native HspX was highly immunogenic and protective, in a dose-dependent manner, in both short- and long-term infection models. Based on these promising findings, HspX was produced as a recombinant protein in E. coli, as this would enable facile purification; however, recombinant HspX (rHspX) alone consistently failed to protect against aerosol challenge. Incubation of rHspX with mycobacterial cell lysate and re-purification following incubation restored the capacity of the protein to confer protection. These data suggest the possibility that the native form may chaperone an immunogenic and protective antigen that is mycobacteria-specific.
Keyword Alpha crystallin
Heat Shock Protein
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Veterinary Science Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
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