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ABSTRACT: Ornithine-containing lipids (OrnL) extracted from Flavobacterium meningosepticum have been reported to have various biological activities such as B-cell mitogenicity and macrophage activation to generate interleukin-1 and prostaglandin E2. We, using ovalbumin (OVA) as an antigen, evaluated the adjuvant activity of OrnL as an immunological adjuvant in BALB/c mice. OrnL showed the function of forming liposome-like vesicles retaining biological activities when prepared as either small unilamellar or dehydration-rehydration vesicles. Although OrnL was not shown to have enough entrapping efficacy for use as a vaccine adjuvant, phosphatidylglycerol (PG) and cholesterol (CHOL) added to stabilize the vesicle membrane increased the entrapping efficacy to the same extent as that of conventional liposomes. Furthermore, the stabilized OrnL vesicles tolerated centrifugation to remove non-entrapped antigens. Completely antigen-entrapped OrnL vesicles including Pg and CHOL induced a significantly greater enhancement of IgG antibody production than did aluminum hydroxide gel in BALB/c mice from week 6. These results indicate that OrnL can be utilized as an immunological adjuvant for vaccines.
Microbiology and Immunology 02/1997; 41(2):101-6. · 1.30 Impact Factor
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ABSTRACT: Aluminum hydroxide (Al) and calcium phosphate (Ca) gels have been used as vaccine adjuvants for many years. We investigated mechanism of the hemolytic activities of both adjuvant materials. The hemolytic activity of each gel depended on the gel dose. The adsorption capacities and the hemolytic activities of both adjuvants decreased as the concentration of phosphate increased in a gel-washing solution. A positive correlation between the hemolytic activity and the adsorption capacity was found in Al-gel. A disruptive effect of Ca-gel on membrane of erythrocytes was shown by electron microscopy. Ca-gel required more than 10 times as much pre-adsorbed ovalbumin as did Al-gel to inhibit the hemolysis. These results suggest that the hemolytic activity of both adjuvant materials depended mainly on the adsorption ability, and it may be useful to control the adsorption ability of adjuvants to reduce their hemolytic activity.
Microbiology and Immunology 02/1994; 38(7):543-8. · 1.30 Impact Factor
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ABSTRACT: Aluminium hydroxide (Al) and calcium phosphate (Ca) have been used for many years as immunological adjuvants for biologicals. We investigated the toxic effects of both adjuvants with different physical properties. Al-gel elicited vascular permeability-increasing and toxic effects to macrophages (M phi), while its haemolytic effect was weak. Ca-gel elicited a significantly stronger haemolytic effect, but no other toxic effect. Incubation of M phi or polymorphonuclear leucocytes with Al-suspension resulted in the largest release of lactate dehydrogenase. Ca-suspension caused haemolysis of about 50% of that caused by Ca-gel.
Vaccine 02/1993; 11(9):914-8. · 3.77 Impact Factor
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ABSTRACT: Effects of calcium phosphate and aluminium hydroxide adjuvants with different physical properties were examined in guinea pigs for local histopathological reactions, electron-microscopical changes of macrophages and adjuvanticity on total IgG antibody response to subcutaneously administered ovalbumin (OVA) and tetanus toxoid (TT). Calcium phosphate gel (Ca-gel) induced active inflammatory reactions consisting of neutrophils (pseudoeosinophils) and foamy macrophages associated with many multinuclear giant cells for at least 4 weeks. Aluminium hydroxide gel (Al-gel) also elicited granulomatous inflammatory reactions consisting mainly of macrophages with foamy cytoplasm, small lymphocytes and giant cells at the injection sites for up to 8 weeks or longer. Severity of local tissue irritation due to calcium phosphate gel (Ca-gel) was similar to that due to Al-gel except for the duration of the inflammatory reactions. Calcium phosphate suspension (Ca-sus)-induced local reactions completely ceased by the 4th week, while aluminium hydroxide suspension (Al-sus)-induced reactions were seen up to the 8th week. Electron-microscopical observations showed that both Al-gel and Al-sus caused damage of macrophages. The adjuvant activity of Al-gel for OVA or TT was significantly stronger than that of any other adjuvant material, whereas those of Ca-gel and Ca-sus were not seen at a dose of 3 mg calcium phosphate per millilitre. Al-sus-TT at a dose of 3 mg aluminium hydroxide per millilitre induced very low levels of antibody. These results suggest that calcium phosphate adjuvant may not be an useful alternative to Al adjuvant.
Vaccine 15(12-13):1364-71. · 3.77 Impact Factor
