Cationic lipid DC-Chol induces an improved and balanced immunity able to overcome the unresponsiveness to the hepatitis B vaccine.
Th1 and Th2 immune responses against antigens can be modulated by the use of adjuvants. Since antibody isotypes (IgG1 and IgG2a) and cytokines induced may reflect the Th differentiation taking place during the immune response, the humoral and cellular immune responses induced in mice against hepatitis B virus surface antigen (HBsAg) were examined when the antigen was either adsorbed to aluminum hydroxyde or administered with a new adjuvant the cationic lipid 3beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol). The use of DC-Chol increased antibody responses in responding BALB/c mice, induced more consistent IgG1 and IgG2a antibody responses in OF1 mice and overcame the nonresponse to HBsAg in B10.M mice. Furthermore, DC-Chol was able to induce cellular immune responses to HBsAg. The DC-Chol induced a balanced Th1/Th2 response, which enabled mice to overcome the inherited unresponsiveness to HBsAg encountered with aluminum-adjuvanted vaccine. Thus, the DC-Chol provides a signal to switch on both Th1 and Th2 responses, which may have important implications for vaccination against hepatitis B virus, as well as for enhancing weak immunogenicity of other recombinant purified antigens in a nonresponder population.
Brunel
F
F
Research Department, Pasteur Mérieux Connaught, Marcy L'Etoile, France.
Darbouret
A
A
Ronco
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D006224:Cricetinae; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000097:blood; D006511:Hepatitis B Antigens / Q000096:biosynthesis / Q000097:blood; D017325:Hepatitis B Vaccines / Q000276:immunology* / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D000536:Aluminum Hydroxide; D002784:Cholesterol