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Sixteen monoclonal antibodies (MAbs) directed against toxic shock syndrome toxin-1 (TSST-1) were generated by immunization of mice with purified TSST-1 and subsequent fusion of spleen cells with myeloma cells. Antibody-producing clones, identified by an enzyme-linked immunosorbent assay, were maintained as ascites tumors, and MAbs were purified by protein A chromatography. High-titered clones were further characterized and tested for the ability to neutralize several biological activities of TSST-1. The MAbs, which are of several immunoglobulin subtypes, reacted specifically with purified TSST-1 and TSST-1 present in Staphylococcus aureus culture supernatants. Three MAbs neutralized TSST-1-induced mitogenesis in a dose-dependent manner. Three of eight MAbs tested were able to neutralize induction by TSST-1 of interleukin-1 production by human monocytes. One neutralizing MAb, 8-5-7, was tested for the ability to protect rabbits from a constant infusion of TSST-1. Rabbits given the MAb had an attenuated clinical illness and were protected from the hypocalcemia, lipemia, and hepatic and renal insufficiency seen in control rabbits. Six of seven control rabbits died, compared with only one of seven rabbits treated with MAb 8-5-7. These experiments suggest that MAb 8-5-7 is directed against an antigenic determinant critical to the toxicity of TSST-1 and that the MAbs should be useful as probes in structure-function analyses of the TSST-1 molecule.

A regimen of immunostimulation with 6-0-stearoyl-N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine, a lipophilic analog of muramyl dipeptide, combined with antimonial drug therapy was evaluated in the treatment of visceral leishmaniasis of mice and hamsters. The combined treatment was found to be more effective in the elimination of Leishmania donovani amastigotes from infected tissue macrophages than was either of the two treatments applied individually. In mice, it was found that immunostimulation of animals prophylactically, therapeutically, or both enhanced the effects of the antimonial drug (Glucantime) administered more than 1 week after a challenge of BALB/c and C57BL/6 mice. The superiority of the combined treatment of the parasite infection was demonstrable in both short-term (14 days) and long-term (40 to 45 days) infections of the two inbred strains of mice. The combined therapy was also effective in preventing the lethal course of leishmaniasis in hamsters which succumb to disseminated disease in the absence of therapeutic intervention. The efficacy of this dual approach to the therapy of disseminated leishmaniasis of experimental animals holds promise for similar application in the treatment of similarly afflicted human populations.