A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival.
Murine mAbs reactive with the surface of Mycobacterium tuberculosis were assayed for their ability to affect the course of infection in mice challenged with virulent organisms. An IgG3 mAb (9d8) specific for arabinomannan and reactive with purified antigen from a clinical isolate of M. tuberculosis conferred partial protection on mice after respiratory challenge (30-60% survival >75 days; P </= 0.05). Control mice pretreated with an irrelevant mAb of the same isotype succumbed to tuberculosis within 30 days. Mice with gene disruptions in interferon gamma and major histocompatibility complex Class II also were partially protected from challenge. The protective mAb was neither bactericidal nor inhibitory of infection or bacterial replication. Nevertheless, it profoundly altered the nature of the granulomas in the infected lungs. Mice treated with mAb 9d8 and challenged with M. tuberculosis localized the pathogen within granuloma centers, suggesting that the mAb conferred protection by enhancing a cellular immune response.
Teitelbaum
R
R
Department of Microbiology and Immunology of the Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10064, USA.
Glatman-Freedman
A
A
Chen
B
B
Robbins
J B
JB
Unanue
E
E
Casadevall
A
A
Bloom
B R
BR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II; D006099:Granuloma / Q000473:pathology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000473:pathology; D008351:Mannans / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D009504:Neutrophils / Q000502:physiology; D015996:Survival Rate; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D014774:Virulence
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D008351:Mannans; C012189:arabinomannan; D007371:Interferon-gamma