Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch

Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Nina Movsesyan, Adrine Karapetyan, David H. Cribbs, Michael G. Agadjanyan

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2275-2282
Number of pages8
JournalVaccine
Volume24
Issue number13
DOIs
StatePublished - Mar 20 2006

Fingerprint

alum
Alzheimer disease
prototypes
epitopes
adjuvants
Antibody Formation
Epitopes
Anti-Idiotypic Antibodies
Alzheimer Disease
Vaccines
vaccines
antibodies
humoral immunity
Immunoglobulin G
B-Lymphocyte Epitopes
Th1 Cells
Meningoencephalitis
T-Lymphocyte Epitopes
Passive Immunization
Amyloid Plaques

Keywords

  • Alzheimer's disease (AD)
  • Epitope vaccine immunization
  • Th1 and Th2 adjuvants

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Ghochikyan, A., Mkrtichyan, M., Petrushina, I., Movsesyan, N., Karapetyan, A., Cribbs, D. H., & Agadjanyan, M. G. (2006). Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch. Vaccine, 24(13), 2275-2282. https://doi.org/10.1016/j.vaccine.2005.11.039

Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch. / Ghochikyan, Anahit; Mkrtichyan, Mikayel; Petrushina, Irina; Movsesyan, Nina; Karapetyan, Adrine; Cribbs, David H.; Agadjanyan, Michael G.

In: Vaccine, Vol. 24, No. 13, 20.03.2006, p. 2275-2282.

Research output: Contribution to journalArticle

Ghochikyan, A, Mkrtichyan, M, Petrushina, I, Movsesyan, N, Karapetyan, A, Cribbs, DH & Agadjanyan, MG 2006, 'Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch', Vaccine, vol. 24, no. 13, pp. 2275-2282. https://doi.org/10.1016/j.vaccine.2005.11.039
Ghochikyan, Anahit ; Mkrtichyan, Mikayel ; Petrushina, Irina ; Movsesyan, Nina ; Karapetyan, Adrine ; Cribbs, David H. ; Agadjanyan, Michael G. / Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch. In: Vaccine. 2006 ; Vol. 24, No. 13. pp. 2275-2282.
@article{3055b79352d94d42a02a7b50d61d7ad4,
title = "Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch",
abstract = "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.",
keywords = "Alzheimer's disease (AD), Epitope vaccine immunization, Th1 and Th2 adjuvants",
author = "Anahit Ghochikyan and Mikayel Mkrtichyan and Irina Petrushina and Nina Movsesyan and Adrine Karapetyan and Cribbs, {David H.} and Agadjanyan, {Michael G.}",
year = "2006",
month = "3",
day = "20",
doi = "10.1016/j.vaccine.2005.11.039",
language = "English (US)",
volume = "24",
pages = "2275--2282",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "13",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=33344460820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33344460820&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2005.11.039

DO - 10.1016/j.vaccine.2005.11.039

M3 - Article

C2 - 16368167

AN - SCOPUS:33344460820

VL - 24

SP - 2275

EP - 2282

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 13

ER -