Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - A novel immunotherapeutic strategy

Nina Movsesyan, Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Hayk Davtyan, Purevdorj B. Olkhanud, Elizabeth Head, Arya Biragyn, David H. Cribbs, Michael G. Agadjanyan

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Background: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Aβ antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Aβ42 (Aβ1-11), a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype. Methods and Findings: We generated pMDC-3Aβ1-11-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Aβ antibody, which in turn inhibited accumulation of Aβ pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. Conclusions: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials.

Original languageEnglish (US)
Article numbere2124
JournalPloS one
Volume3
Issue number5
DOIs
StatePublished - May 7 2008

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DNA Vaccines
Pathology
Chemokine CCL22
epitopes
Epitopes
Vaccines
animal models
vaccines
Anti-Idiotypic Antibodies
DNA
B-Lymphocyte Epitopes
Animals
T-Lymphocyte Epitopes
Immunology
Humoral Immunity
clinical trials
Allergy and Immunology
Immunization
Autoimmunity
Chemokines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Movsesyan, N., Ghochikyan, A., Mkrtichyan, M., Petrushina, I., Davtyan, H., Olkhanud, P. B., ... Agadjanyan, M. G. (2008). Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - A novel immunotherapeutic strategy. PloS one, 3(5), [e2124]. https://doi.org/10.1371/journal.pone.0002124

Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - A novel immunotherapeutic strategy. / Movsesyan, Nina; Ghochikyan, Anahit; Mkrtichyan, Mikayel; Petrushina, Irina; Davtyan, Hayk; Olkhanud, Purevdorj B.; Head, Elizabeth; Biragyn, Arya; Cribbs, David H.; Agadjanyan, Michael G.

In: PloS one, Vol. 3, No. 5, e2124, 07.05.2008.

Research output: Contribution to journalArticle

Movsesyan, N, Ghochikyan, A, Mkrtichyan, M, Petrushina, I, Davtyan, H, Olkhanud, PB, Head, E, Biragyn, A, Cribbs, DH & Agadjanyan, MG 2008, 'Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - A novel immunotherapeutic strategy', PloS one, vol. 3, no. 5, e2124. https://doi.org/10.1371/journal.pone.0002124
Movsesyan N, Ghochikyan A, Mkrtichyan M, Petrushina I, Davtyan H, Olkhanud PB et al. Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - A novel immunotherapeutic strategy. PloS one. 2008 May 7;3(5). e2124. https://doi.org/10.1371/journal.pone.0002124
Movsesyan, Nina ; Ghochikyan, Anahit ; Mkrtichyan, Mikayel ; Petrushina, Irina ; Davtyan, Hayk ; Olkhanud, Purevdorj B. ; Head, Elizabeth ; Biragyn, Arya ; Cribbs, David H. ; Agadjanyan, Michael G. / Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - A novel immunotherapeutic strategy. In: PloS one. 2008 ; Vol. 3, No. 5.
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