The pathogenesis of
Alzheimer's disease (AD) has been strongly associated with the accumulation of
amyloid beta (Aβ)
peptides in brain, and
immunotherapy targeting Aβ provides potential for AD prevention. A clinical trial in which AD patients were immunized with Aβ42
peptide was stopped when 6% of participants showed
meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that Aβ42
DNA vaccination via gene gun generates a Th2 cellular immune response, which was shown by analyses of the respective antibody isotype profiles. We also determined that in vitro T cell proliferation in response to Aβ42
peptide re-stimulation was absent in
DNA Aβ42 trimer-immunized mice when compared to Aβ42
peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune response in wild-type mice after vaccination with Aβ42 trimer
DNA and Aβ42
peptide with
Quil A adjuvant. Wild-type mice were immunized with short-term (1-3× vaccinations) or long-term (6× vacinations) immunization strategies. Antibody titers and isotype profiles of the Aβ42 specific
antibodies, as well as
cytokine profiles and cell proliferation studies from this longitudinal study were determined. Sufficient antibody titers to effectively reduce Aβ42, but an absent T cell proliferative response and no IFNγ or
IL-17 secretion after Aβ42
DNA trimer immunization minimizes the risk of inflammatory activities of the immune system towards the
self antigen Aβ42 in brain. Therefore, Aβ42
DNA trimer immunization has a high probability to be effective and safe to treat patients with early AD.