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

H. Davtyan, Mikayel Mkrtichyan, N. Movsesyan, I. Petrushina, G. Mamikonyan, D. H. Cribbs, M. G. Agadjanyan, A. Ghochikyan

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Recently, we reported that a DNA vaccine, composed of three copies of a self B cell epitope of amyloid-Β (AΒ 42) 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-AΒ 11 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 AΒ 42 peptide. Thus, we showed that a heterologous prime-boost regimen could be an effective protocol for developing a potent Alzheimer's disease (AD) vaccine.

Original languageEnglish (US)
Pages (from-to)261-271
Number of pages11
JournalGene Therapy
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2010

Fingerprint

Recombinant Proteins
Anti-Idiotypic Antibodies
DNA Vaccines
Alzheimer Vaccines
Epitopes
DNA
B-Lymphocyte Epitopes
Synthetic Vaccines
Genetically Modified Animals
Subunit Vaccines
Proteins
T-Lymphocyte Epitopes
Amyloid beta-Protein Precursor
Humoral Immunity
Amyloid
Antibody Formation
Immunoglobulins
Alzheimer Disease
Vaccination
Vaccines

Keywords

  • DNA vaccine
  • Prime-boost regimen
  • Β-amyloid

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Davtyan, H., Mkrtichyan, M., Movsesyan, N., Petrushina, I., Mamikonyan, G., Cribbs, D. H., ... Ghochikyan, A. (2010). DNA prime-protein boost increased the titer, avidity and persistence of anti-AΒ antibodies in wild-type mice. Gene Therapy, 17(2), 261-271. https://doi.org/10.1038/gt.2009.140

DNA prime-protein boost increased the titer, avidity and persistence of anti-AΒ antibodies in wild-type mice. / Davtyan, H.; Mkrtichyan, Mikayel; Movsesyan, N.; Petrushina, I.; Mamikonyan, G.; Cribbs, D. H.; Agadjanyan, M. G.; Ghochikyan, A.

In: Gene Therapy, Vol. 17, No. 2, 01.02.2010, p. 261-271.

Research output: Contribution to journalArticle

Davtyan, H, Mkrtichyan, M, Movsesyan, N, Petrushina, I, Mamikonyan, G, Cribbs, DH, Agadjanyan, MG & Ghochikyan, A 2010, 'DNA prime-protein boost increased the titer, avidity and persistence of anti-AΒ antibodies in wild-type mice', Gene Therapy, vol. 17, no. 2, pp. 261-271. https://doi.org/10.1038/gt.2009.140
Davtyan H, Mkrtichyan M, Movsesyan N, Petrushina I, Mamikonyan G, Cribbs DH et al. DNA prime-protein boost increased the titer, avidity and persistence of anti-AΒ antibodies in wild-type mice. Gene Therapy. 2010 Feb 1;17(2):261-271. https://doi.org/10.1038/gt.2009.140
Davtyan, H. ; Mkrtichyan, Mikayel ; Movsesyan, N. ; Petrushina, I. ; Mamikonyan, G. ; Cribbs, D. H. ; Agadjanyan, M. G. ; Ghochikyan, A. / DNA prime-protein boost increased the titer, avidity and persistence of anti-AΒ antibodies in wild-type mice. In: Gene Therapy. 2010 ; Vol. 17, No. 2. pp. 261-271.
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