Site-specific UBITh amyloid-beta vaccine for immunotherapy of Alzheimer's disease.
The UBITh AD immunotherapeutic vaccine for Alzheimer's disease uses an amyloid-beta (Abeta) immunogen having two designer peptides that have been engineered to elicit anti-N terminal Abeta(1-14) antibodies while minimizing potential for the generation of adverse anti-Abeta 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-Abeta antibodies are generated with the expected N-terminus site-specificity, and that these antibodies have functional immunogenicities to neutralize the toxic activity of Abeta and promote clearance of plaque deposition. The antibodies appear to draw Abeta from the CNS into peripheral circulation. Results indicate that the UBITh AD vaccine did not evoke anti-Abeta 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.
Wang
Chang Yi
CY
United Biomedical Inc., 25 Davids Drive, Hauppauge, NY 11788, USA. cywang@unitedbiomedical.com
Finstad
Connie L
CL
Walfield
Alan M
AM
Sia
Charles
C
Sokoll
Kenneth K
KK
Chang
Tseng-Yuan
TY
Fang
Xin De
XD
Hung
Chung Ho
CH
Hutter-Paier
Birgit
B
Windisch
Manfred
M
D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D007167:Immunotherapy; D008251:Macaca; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D014612:Vaccines