Publications

  • Apr 1 2017

    DP-C016, A PHOSPHOTAU VACCINE WITH ANTI-INFLAMMATORY PROPERTIES

    • Aims: To test the immunogenicity of DP-C016, a phosphotau vaccine op\mized for its ability to be loaded
    onto biodegradable polylactic acid (PLA) i-Particles®.
    • Method: Declensional peptides are amino acid copolymers [e.g., glatiramer acetate (Copaxone®; Teva)]
    with antigen specificity. DP-C016 is a declensional peptide targeting multiple epitopes in the C-terminal
    region of hyperphosphorylated tau. DP-C016 loaded onto 180-nm PLA i-particles was tested for its ability
    to induce human T-cell proliferation in vitro and antibodies in mice.
    • Results: DP-C016, 7.5μM induced proliferation of CD4+ T-cells, between 0.10 and 8.14% above background
    as measured by CFSE incorporation, in PBMCs from 16 of 22 healthy human subjects; loading of DP-C016,
    0.25μM onto PLA i-particles restored CD4+ T-cell proliferation above background in 18 of them (range 0.03
    to +5.34% versus -1.47 to +0.10% for DP-C016 alone). hTau-transgenic JNPL3 mice immunized with DPC016,
    0.3 or 1.2mg/kg formulated with either IFA or PLA i-particles had mostly a Th2-biased, IgG1 antibody
    response, targeting in particular PHF1 (pS396+pS404) and pS422 epitopes. ELISA showed crossreactivity of
    the mouse sera against PHFs isolated from AD patients’ autopsies while IHC demonstrated staining of NFTs,
    plaques and neuropil threads; an\body response to non-phosphorylated recombinant tau was the
    strongest in mice receiving DP-C016, 1.2mg/kg formulated in IFA.
    • Conclusion: DP-C016 formulated with PLA i-par\cles may constitute a safe and stable vaccine to chronically
    treat patients with tauopathies by inducing an\bodies against hyperphosphorylated tau without the
    inflamma\on responsible for harmful encephalopathy and microhemorrhage. We are currently testing DPC016
    peptide for its efficacy in hTau-transgenic mice.