cord-factors and Brucellosis

In a series of studies in SPF and conventional guinea pigs, various adjuvants (larifan, polyoxidonium-PO, natrium thiosulphate-NT, TNF-β and Ribi adjuvant system-RAS) were evaluated for their ability to enhance immune responses to the live brucellosis vaccine, Brucella abortus strain 82-PS (penicillin-sensitive). Combining adjuvants with S82-PS increased synthesis of antibodies against rough (R) and smooth (S) Brucella antigens. Dynamics and levels of antibodies differed dependent upon the adjuvant. Adjuvants enhanced cell-mediated responses to S82-PS, and phagocytosis by macrophages. Humoral and cellular immune responses stimulated by the adjuvants correlated with increased vaccine protection against experimental challenge. The highest protection was demonstrated by combining TNF-β or PO with S82-PS. Our data demonstrates the potential of adjuvants to improve immunogenic properties of live brucellosis vaccines.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Bacterial; Brucella abortus; Brucella Vaccine; Brucellosis; Cell Proliferation; Cell Wall Skeleton; Cord Factors; Guinea Pigs; Immunity, Cellular; Immunity, Humoral; Lipid A; Lymphotoxin-alpha; Macrophages, Peritoneal; Male; Organic Chemicals; Phagocytosis; Piperazines; Polymers

Guinea pigs were subcutaneously inoculated with 300 microgram of Brucella abortus strain 45/20 killed cells combined in 1% oil emulsion with trehalose dimycolate (TDM), muramyl dipeptide (MDP), or a combination of the 2 immunopotentiators. Protection, as determined by splenic infections in the guinea pigs after challenge exposure, was compared with that induced by strain 19 vaccine. With few exceptions, protection induced by bacterins containing 50 to 1,000 microgram of TDM or TDM-MDP/dose was comparable with that of strain 19 vaccine (P greater than 0.05). Bacterins that contained MDP as an adjuvant were inferior to those with TDM regardless of the excipient or method of preparation. There was no further enhancement of immunogenicity by the addition of MDP to bacterins that already contained TDM. Mineral oil could not be replaced by a metabolizable excipient in bacterins potentiated with TDM.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Brucella abortus; Brucella Vaccine; Brucellosis; Cord Factors; Glycolipids; Glycopeptides; Guinea Pigs

A purified protein derivative-live preparation of Brucella abortus strain 45/20 was tested for immunogenic properties either alone, after lipid conjugation, or in association with defined adjuvants. The adjuvants were trehalose dimycolate (cord factor), isolated from wax D of mycobacteria and murmyl dipeptide (N-acetyl-muramyl-L-alamyl-D-isoglutamine), a synthetic glycopeptide analog of peptidoglycan subunits found in many bacterial cell walls and wax D of mycobacteria. Guinea pigs were intradermally inoculated with a single injection of the vaccine preparations eight weeks before intramuscular challenge with B. abortus, strain 2308. None of the purified protein derivative-like preparations were as effective in the prevention of splenic infections with B. abortus as were killed whole cells of strain 45/20 in Freund's complete adjuvant. Whole cells in Freund's complete adjuvant were able to reduce mean colony counts by 97% (P = 0.02), while purified protein derivative-like vaccines were able to reduce mean colony counts by only 32 to 61% as compared to control animals. Results suggest that purified protein derivative-like preparations have limited immunogenic properties under present test conditions.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Antigens, Bacterial; Bacterial Vaccines; Brucella abortus; Brucellosis; Cord Factors; Female; Guinea Pigs; Lauric Acids; Spleen

Whole cells of Brucella abortus strain 45/20 were combined with trehalose dimycolate or muramyl dipeptide. These preparations were tested in guinea pigs for immunogenic properties. Both trehalose dimycolate and muramyl dipeptide were found to be effective adjuvants to whole cells when combined in oil emulsions. Although saline suspensions of whole cells or whole cells-muramyl dipeptide did not significantly reduce splenic infections, oil emulsion or whole cells-trehalose dimycolate in oil droplet emulsion were both effective immunogens (P < 0.05). Oil emulsions of whole cells-muramyl dipeptide reduced mean splenic Brucella by 95.1% and those of whole cells-trehalose dimycolate reduced mean splenic Brucella by 99.3% as compared to the control animals.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Bacterial Vaccines; Brucella abortus; Brucellosis; Cord Factors; Female; Guinea Pigs; Spleen