Passive serum therapy with polyclonal antibodies against Mycobacterium tuberculosis protects against post-chemotherapy relapse of tuberculosis infection in SCID mice.
We investigated the protective role of immune-sera against reactivation of Mycobacterium tuberculosis infection in SCID mice and found that passive immunization with sera obtained from mice treated with detoxified M. tuberculosis extracts (delivered in liposomes in a composition known as RUTI) exerted significant protection. Our SCID mouse model consisted of aerosol infection by M. tuberculosis, followed by 3 to 8weeks of chemotherapy with isoniazid+rifampicin (INH+RIF) (25 and 10mg/kg, respectively). After infection and antibiotic administration, two groups of mice were treated for up to 10weeks with intraperitoneal passive immunization using hyperimmune serum (HS) obtained from mice infected with M. tuberculosis, treated with chemotherapy (INH+RIF) for 8weeks and inoculated with RUTI (HS group) or with normal serum (CT group). Significant differences were found between HS and CT groups in the number of bacilli in the lungs (3.68+/-2.02 vs. 5.72+/-1.41log(10) c.f.u.), extent of pulmonary granulomatomous infiltration (10.33+/-0.67 vs. 31.2+/-1.77%), and percentage of animals without pulmonary abscesses (16.7% vs. 45.5%). These data strongly suggest a protective role of specific antibodies against lung dissemination of M. tuberculosis infection.
Guirado
Evelyn
E
Unitat de Tuberculosi Experimental, Department of Microbiology, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Crta del Canyet s/n, 08916 Badalona, Catalonia, Spain.
Amat
Isabel
I
Gil
Olga
O
Díaz
Jorge
J
Arcos
Virginia
V
Caceres
Neus
N
Ausina
Vicenç
V
Cardona
Pere-Joan
PJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000276:immunology; D000995:Antitubercular Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage* / Q000276:immunology; D007116:Immunization, Passive; D007538:Isoniazid / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012293:Rifampin / Q000627:therapeutic use; D055502:Secondary Prevention; D013047:Specific Pathogen-Free Organisms; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D000995:Antitubercular Agents; D007106:Immune Sera; D007538:Isoniazid; D012293:Rifampin