A mutant of Mycobacterium tuberculosis lacking the 19-kDa lipoprotein Rv3763 is highly attenuated in vivo but retains potent vaccinogenic properties.
A mutant of Mycobacterium tuberculosis (Delta 19) lacking the 19-kDa lipoprotein grows well in culture in vitro but was shown here to be essentially incapable of any significant replication in mice, even in mice lacking the gamma interferon gene. Despite this, mice inoculated with Delta 19 were equally protected against an aerosol delivered challenge with M. tuberculosis compared to the conventional BCG vaccine. Cellular responses, including the generation of activated CD4 and CD8 cells secreting gamma interferon, were produced in similar numbers, and lung cells, particularly dendritic macrophages, exhibited high levels of Class-II MHC expression. These data show that despite being highly attenuated, the Delta 19 mutant strongly retained vaccinogenic properties.
Henao-Tamayo
Marcela
M
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80524, USA. marcela.henao_tamayo@colostate.edu
Junqueira-Kipnis
Ana Paula
AP
Ordway
Diane
D
Gonzales-Juarrero
Mercedes
M
Stewart
Graham R
GR
Young
Douglas B
DB
Wilkinson
Robert J
RJ
Basaraba
Randall J
RJ
Orme
Ian M
IM
D000336:Aerosols; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008074:Lipoproteins / Q000235:genetics*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D014376:Tuberculosis / Q000517:prevention & control; D014774:Virulence