Biologically active components from mycobacterial cell walls. IV. Protection of mice against aerosol infection with virulent mycobacterium tuberculosis.
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Aerosols↗
Biomedical subjects
E Ribi
Publications and source records attributed to E Ribi.
Biologically active components from mycobacterial cell walls. V. Granuloma formation in mouse lungs and guinea pig skin.
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Animals↗
Immunotherapy of cancer: tumor suppression and regression by cell walls of Mycobacterium phlei attached to oil droplets.
Components of mycobacterial cell wall(s) (CW) attached to oil droplets were evaluated for their ability 1) to inhibit the growth of line-10 tumor transplants in the skin of syngeneic guinea pigs when inoculated together with 10(6) tumor cells (suppression experiments) and 2) to regress established 7-day-old intradermal tumors and eradicate microscopic lymph node metastases upon injection into the tumors (regression experiments). CW and cell-wall skeleton (CWS) preparations from Mycobacterium phlei, a fast-growing saprophyte of group IV of the atypical mycobacteria, suppressed tumor growth in essentially all animals when 37.5-mug doses were administered; at a dose of 300 mug, they cured 50-60% of the animals in regression tests. The addition of 300 mug of a purified trehalose mycolate, isolated from M. tuberculosis strain Aoyama B, to 300 mug M. phlei CW or CWS preparations significantly increased their tumor regressive potency to provide cure rates to about 90%. Because M. phlei can be propagated more readily, it can be used advantageously in place of BCG to prepare stable, non-living immunologic adjuvants of defined composition and consistently high potency to meet the need for standards with minimal residual malignant disease.
Animals↗
Migration inhibitory factor and type II interferon in the circulation of mice sensitized with mycobacterial components.
Migration inhibitory factor (MIF) and type II interferon were released into the circulation after mice had been sensitized i.v. with a bacillus of Calmette and Guerin (BCG) cell-wall-in-oil vaccine and then challenged four weeks later with 50 mg old tuberculin. At least two components of BCG, protein (PPD) and lipid (P-3), have been identified which are essential for the type of sensitization in which mediators are released after appropriate challenge. The route of sensitization had a marked effect on the development of delayed footpad reactions, release of lymphokines, and resistance to infection with virulent tubercle bacilli. Sensitization by the subcutaneous route tended to induce more pronounced delayed footpad reactions, whereas the i.v. route of sensitization was associated with maximum release of mediators. A close correlation existed between the conditions of sensitization that resulted in maximum production of lymphokines (MIF and Type II interferon) and those that caused protection against aerosol challenge with a virulent strain of Mycobacterium tuberculosis.
Animals↗
Characterization of a nontoxic monophosphoryl lipid A.
Gram-negative bacterial endotoxins constitute some of the strongest immunologic adjuvants known. Precluding their use as adjuvants in humans has been the exquisite toxicity of these compounds in extraordinarily small amounts. With the acquisition of precise knowledge of the structure of the active moiety, detoxifying procedures have been developed. These have resulted in the isolation of a monophosphoryl lipid A with a much reduced toxicity that retains the capacity to act as an adjuvant in young mice as well as in immunodeficient aging mice.
Adjuvants, Immunologic↗