PMID- 15246623 OWN - NLM STAT- MEDLINE DCOM- 20041018 LR - 20131121 IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 22 IP - 21-22 DP - 2004 Jul 29 TI - Identification of adjuvants that enhance the therapeutic antibody response to host IgE. PG - 2873-80 AB - 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. FAU - Johansson, Jeannette AU - Johansson J AD - Department of Cell and Molecular Biology, Biomedical Center, Box 596, Uppsala University, S-751 24, Sweden. FAU - Ledin, Anna AU - Ledin A FAU - Vernersson, Molly AU - Vernersson M FAU - Lovgren-Bengtsson, Karin AU - Lovgren-Bengtsson K FAU - Hellman, Lars AU - Hellman L LA - eng PT - Journal Article PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Adjuvants, Immunologic) RN - 0 (Autoantibodies) RN - 0 (Autoantigens) RN - 0 (Lipid A) RN - 0 (Plant Oils) RN - 37341-29-0 (Immunoglobulin E) RN - 53678-77-6 (Acetylmuramyl-Alanyl-Isoglutamine) RN - 5QB0T2IUN0 (Aluminum Hydroxide) RN - 8020-83-5 (Mineral Oil) SB - IM MH - Acetylmuramyl-Alanyl-Isoglutamine/pharmacology MH - Adjuvants, Immunologic/*pharmacology MH - Aluminum Hydroxide/pharmacology MH - Animals MH - Autoantibodies/analysis/biosynthesis MH - Autoantigens/immunology MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Hypersensitivity, Immediate/immunology MH - Immunization Schedule MH - Immunization, Secondary MH - Immunoglobulin E/analysis/*biosynthesis/*immunology MH - Lipid A/pharmacology MH - Mineral Oil/pharmacology MH - Opossums/immunology MH - Plant Oils/pharmacology MH - Rats MH - Rats, Wistar EDAT- 2004/07/13 05:00 MHDA- 2004/10/19 09:00 CRDT- 2004/07/13 05:00 PHST- 2003/07/15 00:00 [received] PHST- 2003/12/24 00:00 [accepted] PHST- 2004/07/13 05:00 [pubmed] PHST- 2004/10/19 09:00 [medline] PHST- 2004/07/13 05:00 [entrez] AID - S0264410X04000131 [pii] AID - 10.1016/j.vaccine.2003.12.029 [doi] PST - ppublish SO - Vaccine. 2004 Jul 29;22(21-22):2873-80. doi: 10.1016/j.vaccine.2003.12.029.