DNA Aβ42 immunization via needle-less Jet injection in mice and rabbits as potential immunotherapy for Alzheimer's disease

Doris Lambracht-Washington, Min Fu, Mary Wight-Carter, Matthew Riegel, Linda S. Hynan, Roger N. Rosenberg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Alzheimer's disease (AD) is the most common form of dementia found in the elderly and disease progression is associated with accumulation of Amyloid beta 1–42 (Aβ42) in brain. An immune-mediated approach as a preventive intervention to reduce amyloid plaques without causing brain inflammation is highly desirable for future clinical use. Genetic immunization, in which the immunizing agent is DNA encoding Aβ42, has great potential because the immune response to DNA delivered into the skin is generally non-inflammatory, and thus differs quantitatively and qualitatively from immune responses elicited by peptides, which are inflammatory with production of IFNγ and IL-17 cytokines by activated T cells. DNA immunization has historically been proven difficult to apply to larger mammals. A potential barrier to use DNA immunization in large mammals is the method for delivery of the DNA antigen. We tested jet injection in mice and rabbits and found good antibody production and safe immune responses (no inflammatory cytokines). We found significant reduction of amyloid plaques and Aβ peptides in brains of the DNA Aβ42 immunized 3xTg-AD mouse model. This study was designed to optimize DNA delivery for possible testing of the DNA Aβ42 vaccine for AD prevention in a clinical trial.

Original languageEnglish (US)
Article number120564
JournalJournal of the Neurological Sciences
Volume446
DOIs
StatePublished - Mar 15 2023

Keywords

  • Alzheimer's disease
  • DNA vaccine
  • Immunotherapy
  • Jet injection
  • Large mammals
  • Mouse models
  • Nesting behavior

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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