Identification of adjuvants that enhance the therapeutic antibody response to host IgE.
In the development of a novel vaccine against atopic allergies, we have screened for adjuvants that enhance the therapeutic antibody response against self immunoglobulin E (IgE). The response against self IgE is induced by administration of a vaccine antigen, which contains both self and non-self IgE regions, together with an adjuvant. We evaluated five commonly used adjuvants; Freund's, aluminium hydroxide, ISCOMs, Montanide ISA 51 and Montanide ISA 720, and found that the mineral oil-based adjuvants; Montanide ISA 51 and Freund's induced at least 5-10-fold higher anti-self IgE titers than any of the other candidates. However, with one exception, Alum, the immune responses against the carrier, i.e. the non-self regions, were similar for all adjuvants, indicating that the ability to induce responses against self and non-self antigens differ among adjuvants. The responses against non-self IgE were more than 50-fold higher than antibody responses against self IgE in both the Freund's and Montanide 51-administered animals, indicating that the response against self molecules is markedly inhibited by tolerance-inducing mechanisms. Co-administration of Montanide ISA 51 with immuno-stimulatory substances from bacteria; muramyldipeptide (MDP), monophosphoryl-lipid A (MPL) or a formyl-methionine-containing tripeptide (fMLP), did not elevate the anti-self IgE response. Hence, adjuvants based on pure mineral oil without additional immuno-stimulatory substances appear to be the best adjuvant candidates in therapeutic vaccines aimed at regulating the in vivo levels of self-proteins.
Johansson
Jeannette
J
Department of Cell and Molecular Biology, Biomedical Center, Box 596, Uppsala University, S-751 24, Sweden.
Ledin
Anna
A
Vernersson
Molly
M
Lövgren-Bengtsson
Karin
K
Hellman
Lars
L
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology*; D008050:Lipid A / Q000494:pharmacology; D008899:Mineral Oil / Q000494:pharmacology; D009893:Opossums / Q000276:immunology; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D001324:Autoantigens; D008050:Lipid A; D010938:Plant Oils; D007073:Immunoglobulin E; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000536:Aluminum Hydroxide; D008899:Mineral Oil