Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid.
The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by antisera from mice administrated with Abeta(42) peptide formulated in complete Freund's adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Abeta(42) mixed with QS21 induced a significant antibody response to the 6-20 peptide. The only T cell epitope found was within the 6-28 sequence of Abeta(42). QS21 and CFA induced the strongest humoral response to Abeta, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Abeta indicates that alum induces primarily T(h)2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a T(h)1 phenotype. Stimulation of splenocytes from Abeta-immunized mice with Abeta(40) peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-gamma, IL-4 and tumor necrosis factor-alpha expression, whereas alum induced primarily IL-4 production. As T(h)1-type immune responses have been implicated in many autoimmune disorders, whereas T(h)2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer's disease.
Cribbs
David H
DH
Institute for Brain Aging and Dementia, University of California Irvine, Irvine, CA 92697-4540, USA.
Ghochikyan
Anahit
A
Vasilevko
Vitaly
V
Tran
Mike
M
Petrushina
Irina
I
Sadzikava
Nadya
N
Babikyan
Davit
D
Kesslak
Patrick
P
Kieber-Emmons
Thomas
T
Cotman
Carl W
CW
Agadjanyan
Michael G
MG
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D018604:Epitope Mapping; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D016229:Amyloid beta-Peptides; D016207:Cytokines; D007074:Immunoglobulin G; D010446:Peptide Fragments; D012503:Saponins; C075222:amyloid beta-protein (1-42); C041524:aluminum sulfate; C078785:saponin QA-21V1