DNA immunization with HBsAg-based particles expressing a B cell epitope of amyloid β-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease

Purevdorj B. Olkhanud, Mohammed Mughal, Koichi Ayukawa, Enkhzol Malchinkhuu, Monica Bodogai, Neil Feldman, Sarah Rothman, Jong Hwan Lee, Srinivasulu Chigurupati, Eitan Okun, Kunio Nagashima, Mark P. Mattson, Arya Biragyn

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is an incurable and progressive neurodegenerative senile disorder associated with the brain accumulation of Aβ plaques. Although vaccines that reduce Aβ plaques can control AD, the rationale for their use at the onset of the disease remains debatable. Old humans and mice usually respond poorly to vaccines due to presumably age-related immunological impairments. Here, we report that by modifying vaccines, the poor responsiveness of old mice can be reversed. Unlike the Aβ peptide vaccine, DNA immunizations with the amino-terminal Aβ(1-11) fragment exposed on the surface of HBsAg particles elicit high levels of anti-Aβ antibody both in young and old mice. Importantly, in AD model 3xTgAD mice, the vaccine reduced Aβ plaques, ameliorated cognitive impairments and, surprisingly, significantly increased life span. Hence, we propose that vaccines targeting Aβ(1-11) can efficiently combat AD-induced pathological alterations and provide survival benefit in patients with AD.

Original languageEnglish (US)
Pages (from-to)1650-1658
Number of pages9
JournalVaccine
Volume30
Issue number9
DOIs
StatePublished - Feb 21 2012
Externally publishedYes

Keywords

  • Alzheimer's disease vaccine
  • Life span
  • Old age

ASJC Scopus subject areas

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

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  • Cite this

    Olkhanud, P. B., Mughal, M., Ayukawa, K., Malchinkhuu, E., Bodogai, M., Feldman, N., Rothman, S., Lee, J. H., Chigurupati, S., Okun, E., Nagashima, K., Mattson, M. P., & Biragyn, A. (2012). DNA immunization with HBsAg-based particles expressing a B cell epitope of amyloid β-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease. Vaccine, 30(9), 1650-1658. https://doi.org/10.1016/j.vaccine.2011.12.136