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P4‐401: Combination Therapy with a Plaque‐Specific Abeta Antibody And A Bace Inhibitor Results in Dramatic Plaque Reduction in a Dose‐Dependent Manner in Aged Pdapp Transgenic Mice
Author(s) -
Hole Justin T.,
Racke Margaret M.,
Tzaferis John A.,
Liu Feng,
Oluoch Herold,
Ahmed Zeshan,
Fisher Alice,
Anderson Wesley,
Iversent Philip,
Gonzales Celedon,
Yang Zhixiang,
Boggs Leonard N.,
Monk Scott A.,
Mergott Dustin J.,
Yang Ying YT.,
Lu Jirong,
Irizarry Michael C.,
Sims John R.,
May Patrick C.,
Hutton Michael,
Nordstedt Christer,
DeMattos Ronald B.
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.2016.07.146
Subject(s) - medicine , combination therapy , antibody , pharmacology , pathological , gastroenterology , immunology
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