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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 21, 2023
Accepted:
January 19,
2023
Received in revised form:
January 11,
2023
Received:
May 13,
2022
Identification
Copyright
Published by Elsevier B.V.
