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 8 weeks of chemotherapy with isoniazid + rifampicin (INH + RIF) (25 and 10 mg/kg, respectively). After infection and antibiotic administration, two groups of mice were treated for up to 10 weeks with intraperitoneal passive immunization using hyperimmune serum (HS) obtained from mice infected with M. tuberculosis, treated with chemotherapy (INH + RIF) for 8 weeks 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 +/- 1.41 log(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. (c) 2006 Elsevier SAS. All rights reserved.