DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation.

The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (A?) peptides in brain, and immunotherapy targeting A? provides potential for AD prevention. A clinical trial in which AD patients were immunized with A?42 peptide was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that A?42 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 A?42 peptide re-stimulation was absent in DNA A?42 trimer-immunized mice when compared to A?42 peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune response in wild-type mice after vaccination with A?42 trimer DNA and A?42 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 A?42 specific antibodies, as well as cytokine profiles and cell proliferation studies from this longitudinal study were determined. Sufficient antibody titers to effectively reduce A?42, but an absent T cell proliferative response and no IFN? or IL-17 secretion after A?42 DNA trimer immunization minimizes the risk of inflammatory activities of the immune system towards the self antigen A?42 in brain. Therefore, A?42 DNA trimer immunization has a high probability to be effective and safe to treat patients with early AD.     «

The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (A?) peptides in brain, and immunotherapy targeting A? provides potential for AD prevention. A clinical trial in which AD patients were immunized with A?42 peptide was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that A?42 DNA vaccination via gene gun generates a Th2 cellular immun...     »