Immunological consequences of three doses of heat-killed Mycobacterium vaccae in the immunotherapy of tuberculosis

Abstract

We report the first study of triple-dose immunotherapy with heat-killed Mycobacterium vaccae (SRL 172) combined with short-course, directly observed chemotherapy in newly diagnosed pulmonary tuberculosis patients. The study was carried out in Rosario, Argentina, where single-dose immunotherapy with M. vaccae has previously been shown effective. Twenty-two HIV seronegative patients, sputum-positive for tubercle bacilli, entered a randomised and partly blinded trial. Twelve patients received injections of SRL 172 and 10 patients received placebo on days 1, 30 and 60 of chemotherapy. All patients were followed up clinically, by sputum bacteriology, chest radiography and haematology. Patients receiving SRL 172 showed faster and more complete clinical improvement, accelerated disappearance of bacilli from sputum, better radiological clearance and a more rapid fall in ESR, than did those receiving placebo. Follow-up continued for a year after therapy and no patient failed treatment or relapsed. Special investigations included longitudinal assessments of respiratory bursts and expression of CD11b on separated polymorphonuclear and mononuclear leukocytes. Tumour necrosis factor alpha (TNF-alpha) was measured in the supernates of cultured cells and both TNF-alpha and interleukin-4 (IL-4) were measured in serum samples. Immunotherapy recipients showed a significantly faster return towards normal values in all the immunological parameters, than did placebo recipients. The results are consistent with a regulatory activity on cellular immunity, reducing the influence of Th2 and enhancing Th1 to the benefit of the patients. This could allow a reduced period of chemotherapy without loss of efficacy and help to prevent the development of multi-drug resistance.

Impaired Gamma Interferon Response to Mycobacterium vaccae Antigens in Patients with Cavitary Pulmonary Tuberculosis

“…Johnson et al (7) specifically analyzed the effect of one injected dose of M. vaccae on radiographic response in three large trials and did not observe any benefit. On the contrary, studies in which three or five doses of M. vaccae were administered showed its efficacy for healing and closing cavities in TB patients (4,14). These previous studies together with our results lead us to believe that patients showing an impaired M. vaccae-induced IFN-␥ response in vitro will not respond to one dose of M. vaccae administration in vivo.…”

Vaccine against tuberculosis: what’s new?

“…Clinical trials showed conflicting results [89]. A meta-analysis on MV added TB chemotherapy in never-treated TB patients, showed that it is effective in improving both sputum conversion and X-ray imagines [90].…”

Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues

“…In pulmonary tuberculosis patients, heat-killed mycobacterium vaccine (SRL 172) reduced the influence of Th2 and enhancing Th1 to the benefit of the patients [17]. Several studies have also proved the safety of HKMT when used as adjuvant [18,19].…”