TY - JOUR
T1 - Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch
AU - Ghochikyan, Anahit
AU - Mkrtichyan, Mikayel
AU - Petrushina, Irina
AU - Movsesyan, Nina
AU - Karapetyan, Adrine
AU - Cribbs, David H.
AU - Agadjanyan, Michael G.
N1 - Funding Information:
This work was supported in part by NIH grants AG 20241 (D.H.C. and M.G.A.) NS 50895 (D.H.C. and M.G.A.), IIRG 03-6279 (M.G.A.), and AI 44809 (M.G.A.).
PY - 2006/3/20
Y1 - 2006/3/20
N2 - β-Amyloid (Aβ) peptide has been proposed to be a causal factor in Alzheimer's disease (AD). Currently being investigated, active and passive Aβ-immunotherapy significantly reduce Aβ plaque deposition, neuritic dystrophy, and astrogliosis in the brains of APP transgenic (APP/Tg) mice. Immunization with Aβ42 formulated in the Th1-type adjuvant QS21 was beneficial for AD patients with significant titers of anti-Aβ antibodies, however, 6% of participants developed meningoencephalitis, likely due to anti-Aβ-specific autoimmune Th1 cells. Thus, successful Aβ vaccination requires the development of strong antibody responses without Th1-type cellular immunity. In this study, we compared the induction of humoral immune responses with Th1-type (Quil A) and Th2-type (Alum) adjuvants singly and in combination, using our novel epitope vaccine composed of self B cell epitope Aβ1-15 and foreign T cell epitope PADRE (PADRE-Aβ 1-15-MAP). Formulated in Quil A, this vaccine resulted in significantly higher anti-Aβ antibody responses in both BALB/c (H-2 d) and C57BL/6 (H-2b) mice, compared with Alum. Anti-Aβ antibodies induced by Alum were predominantly IgG1 type accompanied by lower levels of IgG2a and IgG2b. Quil A induced robust and almost equal titers of anti-Aβ antibodies of IgG1 and IgG2a isotypes and slightly lower levels of IgG2b. Switching adjuvants from Alum to Quil A induced higher concentrations of antibodies than injections with Alum only, however slightly lower than Quil A only. Switching both adjuvants did not change the profile of antibody responses generated by the initial adjuvant injected. These results suggest that switching from Alum to Quil A would be beneficial for AD patients because anti-Aβ antibody production was enhanced without changing the initially generated and likely beneficial Th2-type humoral response.
AB - β-Amyloid (Aβ) peptide has been proposed to be a causal factor in Alzheimer's disease (AD). Currently being investigated, active and passive Aβ-immunotherapy significantly reduce Aβ plaque deposition, neuritic dystrophy, and astrogliosis in the brains of APP transgenic (APP/Tg) mice. Immunization with Aβ42 formulated in the Th1-type adjuvant QS21 was beneficial for AD patients with significant titers of anti-Aβ antibodies, however, 6% of participants developed meningoencephalitis, likely due to anti-Aβ-specific autoimmune Th1 cells. Thus, successful Aβ vaccination requires the development of strong antibody responses without Th1-type cellular immunity. In this study, we compared the induction of humoral immune responses with Th1-type (Quil A) and Th2-type (Alum) adjuvants singly and in combination, using our novel epitope vaccine composed of self B cell epitope Aβ1-15 and foreign T cell epitope PADRE (PADRE-Aβ 1-15-MAP). Formulated in Quil A, this vaccine resulted in significantly higher anti-Aβ antibody responses in both BALB/c (H-2 d) and C57BL/6 (H-2b) mice, compared with Alum. Anti-Aβ antibodies induced by Alum were predominantly IgG1 type accompanied by lower levels of IgG2a and IgG2b. Quil A induced robust and almost equal titers of anti-Aβ antibodies of IgG1 and IgG2a isotypes and slightly lower levels of IgG2b. Switching adjuvants from Alum to Quil A induced higher concentrations of antibodies than injections with Alum only, however slightly lower than Quil A only. Switching both adjuvants did not change the profile of antibody responses generated by the initial adjuvant injected. These results suggest that switching from Alum to Quil A would be beneficial for AD patients because anti-Aβ antibody production was enhanced without changing the initially generated and likely beneficial Th2-type humoral response.
KW - Alzheimer's disease (AD)
KW - Epitope vaccine immunization
KW - Th1 and Th2 adjuvants
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U2 - 10.1016/j.vaccine.2005.11.039
DO - 10.1016/j.vaccine.2005.11.039
M3 - Article
C2 - 16368167
AN - SCOPUS:33344460820
SN - 0264-410X
VL - 24
SP - 2275
EP - 2282
JO - Vaccine
JF - Vaccine
IS - 13
ER -