Immunological diversity within a family of cutinase-like proteins of Mycobacterium tuberculosis.
Secreted proteins of Mycobacterium tuberculosis play key roles in the assembly of the mycobacterial cell wall, with many being major targets of the host immune response. To date, meaningful characterization of a significant proportion of this important group of proteins is lacking. Among the group of putatively secreted proteins of M. tuberculosis are 7 cutinase-like proteins (CLP), not previously characterized in terms of their immunogenicity or vaccine protective efficacy. Although the CLP vary in the degree of homology with one another, they all share a similar active catalytic triad, closely homologous to that of the cutinase of Fusarium solani. By construction of DNA vaccines of all 7 CLP, and expression and purification of soluble, recombinant CLP, this study addresses the immunological responses to these proteins. Clp1, 2, 3 and 6 were found to elicit significant IFN-gamma secretion in DNA immunized mice, with the antigens also demonstrating specificity in terms of CLP-generated T cell IFN-gamma release, with minimal cross reactivity of humoral responses. Finally, following delivery of DNA vaccines, Clp1, 2 and 6, conferred a moderate yet reproducible and significant level of protection in a murine aerosol model of M. tuberculosis infection.
West
Nicholas P
NP
Mycobacterial Research Program, Centenary Institute of Cancer Medicine and Cell Biology. Locked Bag 6, Newtown, NSW 2042, Australia. n.west@centenary.org.au
Wozniak
Teresa M
TM
Valenzuela
Jesus
J
Feng
Carl G
CG
Sher
Alan
A
Ribeiro
Jose M C
JM
Britton
Warwick J
WJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D005260:Female; D005670:Fusarium / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D002265:Carboxylic Ester Hydrolases; C019952:cutinase