期刊
VACCINE
卷 25, 期 16, 页码 3041-3052出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2007.01.031
关键词
Alzheimer disease immunotherapy; A beta vaccine; APP transgenic mice; non-human primate toxicology
The UBITh (R) AD immunotherapeutic vaccine for Alzheimer's disease uses an amyloid-beta (A beta) immunogen having two designer peptides that have been engineered to elicit anti-N terminal A beta(1-14) antibodies while minimizing potential for the generation of adverse anti-A beta immune responses. The vaccine has been further designed for minimization of inflammatory reactivities through the use of a proprietary vaccine delivery system that biases Th2 type regulatory T cell responses in preference to Th1 pro-inflammatory T cell responses. In vitro studies and in vivo studies in small animals, baboons and macaques show that anti-A beta antibodies are generated with the expected N-terminus site-specificity, and that these antibodies have functional immunogenicities to neutralize the toxic activity of A beta and promote clearance of plaque deposition. The antibodies appear to draw A beta from the CNS into peripheral circulation. Results indicate that the UBITh (R) AD vaccine did not evoke anti-A beta cellular responses in a transgenic mouse model for AD. The vaccine was safe and well tolerated in adult Cynomolgus macaques during a repeat dose acute and chronic toxicity study. (c) 2007 Elsevier Ltd. All rights reserved.
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