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Mycobacterial Substitutes in "Complete" Freund's Adjuvant¹

Effect on Antibody Production and Delayed Hypersensitivity to Bovine Serum Albumin

From the Departments of Medicine and Microbiology (Clinical Immunology), Louisiana State University School of Medicine, New Orleans, Louisiana

Abstract

Known granuloma-producing agents in man were substituted for mycobacteria in Freund's complete adjuvant. Observations were made on the type and extent of granuloma formation, antibody production and the development of delayed hypersensitivity to an incorporated protein antigen (bovine serum albumin) in rabbits and guinea pigs, and the results were compared with those obtained using Freund's "complete" (mycobacteria) and "incomplete" adjuvants.

The results indicate that none of the granuloma-producing substitutes were comparable in their enhancing effect to crude whole Mycobacterium tuberculosis.

Animals of all groups developed intense granulomatous reactions at the local toe or foot pad inoculation site but only mycobacterial adjuvant resulted in an extensive and widespread epithelioid cell response throughout the reticuloendothelial system plus uniform high levels of circulating antibody and intense delayed hypersensitivity to BSA, suggesting an association between macrophage response and overall adjuvant activity.

Occasional animals in the mycobacteria substitute groups were good antibody producers and developed strong delayed hypersensitivity reactions to BSA without extensive granuloma formation, thus indicating that quantity of granuloma formation per se was not related to adjuvant effect.

There was no relationship between intensity or appearance of delayed hypersensitivity and antibody production to BSA in individual animals during the course of the study.

Footnotes

This work was supported by the United States Public Health Service Research Grant AI-05754.