Low concentrations of anti-Aβ antibodies generated in Tg2576 mice by DNA epitope vaccine fused with 3C3d molecular adjuvant do not affect AD pathology

Nina Movsesyan, Hayk Davtyan, Mikayel Mkrtichyan, Irina Petrushina, Tigran Tiraturyan, Ted Ross, Michael G. Agadjanyan, Anahit Ghochikyan, David H. Cribbs

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7 Scopus citations

Abstract

It has been demonstrated that an active vaccination strategy with protein- or DNA-based epitope vaccines composed of the immunodominant self B cell epitope of amyloid-β42 (Aβ42) and a non-self T helper (Th) cell epitope is an immunotherapeutic approach to preventing or treating Alzheimer's disease (AD). As a DNA-based epitope vaccine, we used a plasmid encoding three copies of Aβ1-11 and Th cell epitope, PADRE (p3Aβ1-11-PADRE). We have previously reported that three copies of component of complement C3d (3C3d) acts as a molecular adjuvant significantly enhancing immune responses in wild-type mice of the H2b haplotype immunized with p3Aβ1-11-PADRE. Here, we tested the efficacy of p3Aβ1-11-PADRE and the same vaccine fused with 3C3d (p3Aβ1-11-PADRE-3C3d) in a transgenic (Tg) mouse model of AD (Tg2576) of the H2bxs immune haplotype. The overall responses to both vaccines were very weak in Tg2576 mice despite the fact that the 3C3d molecular adjuvant significantly enhanced the anti-Aβ response to 3Aβ1-11-PADRE. Importantly, generation of low antibody responses was associated with the strain of amyloid precursor protein Tg mice rather than with a molecular adjuvant, as a p3Aβ1-11-PADRE-3C3d vaccine induced significantly higher antibody production in another AD mouse model, 3xTg-AD of the H2b haplotype. Finally, this study demonstrated that low concentrations of antibodies generated by both DNA vaccines were not sufficient for the reduction of Aβ pathology in the brains of vaccinated Tg2576 animals, confirming previous reports from preclinical studies and the AN-1792 clinical trials, which concluded that the concentration of anti-Aβ antibodies may be essential for the reduction of AD pathology.

Original languageEnglish (US)
Pages (from-to)1569-1576
Number of pages8
JournalHuman Gene Therapy
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Movsesyan, N., Davtyan, H., Mkrtichyan, M., Petrushina, I., Tiraturyan, T., Ross, T., Agadjanyan, M. G., Ghochikyan, A., & Cribbs, D. H. (2010). Low concentrations of anti-Aβ antibodies generated in Tg2576 mice by DNA epitope vaccine fused with 3C3d molecular adjuvant do not affect AD pathology. Human Gene Therapy, 21(11), 1569-1576. https://doi.org/10.1089/hum.2009.219