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

Published:January 21, 2023DOI:https://doi.org/10.1016/j.jns.2023.120564

      Highlights

      • DNA Aβ42 immunization via Jet injection into the skin induced high antibody responses in mice and rabbits.
      • DNA Aβ42 immunization via Jet injection into the skin did not lead to inflammatory cellular responses.
      • DNA Aβ42 immunization via Jet injection into the skin resulted in amyloid removal from brain in the 3xTg-AD mouse model.
      • DNA Aβ42 immunization via Jet injection into the skin improved nesting behavior in the 3xTg-AD mouse model.

      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.

      Keywords

      Abbreviations:

      AD (Alzheimer's disease), ASC (antibody-secreting cells), amyloid precursor protein (APP), Amyloid beta peptide 1–42 (Aβ42), CBC (Complete Blood Counts), ELISA (Enzyme-linked immunosorbent assay), ELISPOT (Enzyme-Linked ImmunoSpot), HRP (horseradish peroxidase), ISC (Immunoglobulin secreting cells), IFNγ (Interferon gamma), IL-17 (Interleukin 17), moab (monoclonal antibody), PBS (Phosphate Buffered Saline)
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