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DNA prime–protein boost increased the titer, avidity and persistence of anti-Aβ antibodies in wild-type mice

Gene Therapy volume 17, pages 261–271 (2010)Cite this article

Abstract

Recently, we reported that a DNA vaccine, composed of three copies of a self B cell epitope of amyloid-β (Aβ42) and the foreign T-cell epitope, Pan DR epitope (PADRE), generated strong anti-Aβ immune responses in wild-type and amyloid precursor protein transgenic animals. Although DNA vaccines have several advantages over peptide–protein vaccines, they induce lower immune responses in large animals and humans compared with those in mice. The focus of this study was to further enhance anti-Aβ11 immune responses by developing an improved DNA vaccination protocol of the prime–boost regimen, in which the priming step would use DNA and the boosting step would use recombinant protein. Accordingly, we generated DNA and recombinant protein-based epitope vaccines and showed that priming with DNA followed by boosting with a homologous recombinant protein vaccine significantly increases the anti-Aβ antibody responses and do not change the immunoglobulin G1 (IgG1) profile of humoral immune responses. Furthermore, the antibodies generated by this prime–boost regimen were long-lasting and possessed a higher avidity for binding with an Aβ42 peptide. Thus, we showed that a heterologous prime–boost regimen could be an effective protocol for developing a potent Alzheimer's disease (AD) vaccine.

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Acknowledgements

We thank Charles Bon and Caroline Pearson, Biostudy Solutions LLC for the pharmacokinetic and statistical analyses. We also thank Anna Agadjanyan for help with editing. This work was supported by funding from the National Institutes of Health: AG20241 (DHC and MGA), NS50895 (DHC & MGA), NS057395 (MGA) and from the Alzheimer's Association IIRG0728314 (AG). NM was supported by the National Institute on Aging training Grant AG00096.

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Authors and Affiliations

  1. Department of Molecular Immunology, The Institute for Molecular Medicine, Huntington Beach, CA, USA

    H Davtyan, M Mkrtichyan, G Mamikonyan, M G Agadjanyan & A Ghochikyan

  2. The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA

    N Movsesyan, I Petrushina, D H Cribbs & M G Agadjanyan

  3. Department of Neurology, University of California, Irvine, CA, USA

    D H Cribbs

  4. Mechnikov Research Institute of Vaccines and Sera, Russian Academy of Medical Sciences, Moscow, Russia

    M G Agadjanyan

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  1. H Davtyan
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Davtyan, H., Mkrtichyan, M., Movsesyan, N. et al. DNA prime–protein boost increased the titer, avidity and persistence of anti-Aβ antibodies in wild-type mice. Gene Ther 17, 261–271 (2010). https://doi.org/10.1038/gt.2009.140

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