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P4‐400: Novel Amyloid‐β Oligomer‐Specific Epitopes: a Hypothesis Driven Approach to Alzheimer's Immunotherapeutics
Author(s) -
Silverman Judith M.,
Gibbs Ebrima,
Wang Jing,
Peng Xubiao,
Plotkin Steve,
Cashman Neil R.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.07.145
Subject(s) - epitope , oligomer , monoclonal antibody , antibody , neurotoxicity , monomer , fibril , chemistry , amyloid (mycology) , linear epitope , epitope mapping , immunoprecipitation , biochemistry , microbiology and biotechnology , biophysics , biology , immunology , toxicity , inorganic chemistry , organic chemistry , polymer
lowed. Results:High antibody responses were found in both species. In the rabbit, 277.16 118.4 mg/ml plasmaweremeasured after 5 immunizations with no significant differences between the dose groups. Antibody levels declined slightly to 246.66 109.5 mg/ml after a resting period of two months. Low levels of IFNg and IL-17 secreting splenocytes were found in the ELISPOTassays from rabbit splenocytes. Rhesusmonkeys reachedmean antibody levels of 114.2 6 41.67 mg/ml plasma after five immunizations. The isotype profile was high on IgG4 antibodies, indicative of a Th2 immune response. After three immunizations, no IL-17 or IFNg producing cells were found in ELISPOT assays from PBMCs. Conclusions: DNA Ab42 immunization leads to high antibody titers in large mammals, and is likely to produce high antibody levels and a safe (Th2 biased) immune response in humans as well. supported by NIA/NIH P30AG12300-21, Zale Foundation, Rudman Foundation, AWARE, Presbyterian Village North, Freiberger, and Denker Family Funds