Humoral immune responses in mice using gamma inulin preparations as adjuvants for hepatitis B vaccines.
There is an urgent need for new, powerful adjuvants suitable for use with sub-unit and peptide vaccines in humans. We have measured the humoral immune response in BALB/c mice to vaccine formulations using recombinant HBsAg antigens, and gamma inulin and alum adjuvants. Using Merck, Sharpe & Dohme (MSD) HBsAg at 10 micrograms/mL, high levels of anti-HBs were generated and geometric mean S/N ratios of 88, 133 and 107 were obtained for alum absorbed vaccine, gamma inulin, and a mixture of the two adjuvants, respectively. A dilution series produced ED50 values of 0.08, 0.15 and 0.22 micrograms/mL respectively. In a second series of experiments comparing alum and algamulin (a complex of gamma inulin and alum), MSD HBsAg induced anti-HBs levels of 81 and 52, and ED50 values of 0.3 and 0.4 when used in conjunction with alum and algamulin, respectively. SKF HBsAg induced anti-HBs levels of 126 and 111 with alum and algamulin, and ED50 values of 0.11 and 0.075. The class, subclass and level of antibody produced in mice boosted with a second dose of vaccine at 21 days was also examined. Both alum and gamma inulin induced higher levels of total antibody, IgG1 and minor IgG subclasses than algamulin, or HBsAg alone. Overall, gamma inulin appears to be an equivalent adjuvant to alum, although their mechanisms of action are different. Mixtures or complexes of the two adjuvants appear to be less effective in inducing humoral immune responses in mice than either alone.
Virology Department, Fairfield Hospital, Melbourne, Vic., Australia.
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DE
Leslie
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Nicholson
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M
Dimitrakakis
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N
Johnston
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Gust
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000939:Epitopes; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology*; D017325:Hepatitis B Vaccines; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D007444:Inulin / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014761:Viral Hepatitis Vaccines; C041524:aluminum sulfate; D007444:Inulin