Virus-like peptide vaccines against Abeta N-terminal or C-terminal domains reduce amyloid deposition in APP transgenic mice without addition of adjuvant.
Immunotherapy against the Abeta peptide is increasingly viewed as an effective means of preventing and even decreasing Abeta deposition in transgenic mouse models and human cases of Alzheimer's disease. A prior active immunization trial was halted due to adverse events which occurred subsequent to a change in the adjuvant used in the vaccine preparation. Although widely used in experimental studies, adjuvants available for use in vaccines intended for humans are limited. We compared two vaccine preparations in which an immunogenic bacteriophage was conjugated with either an N-terminal (Abeta1-9) or C-terminal (Abeta28-40) peptide sequence from the Abeta molecule. We found that both produced significant antibody titers without use of additional adjuvants. Surprisingly, the response to the N terminal sequence was comprised largely of a stable IgM response, while the C-terminal vaccine produced an IgG response with minimal IgM reactivity. Both of these immunogens reduced Abeta levels when tissues were examined 8 months after the first inoculation. These data demonstrate that (a) C-terminal specific vaccines can effectively lower Abeta and (b) IgM antibodies against Abeta may be capable of lowering Abeta, possibly through action in the brain rather than the periphery.
Li
Qing-you
QY
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
Gordon
Marcia N
MN
Chackerian
Bryce
B
Alamed
Jennifer
J
Ugen
Kenneth E
KE
Morgan
Dave
D
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000138:chemical synthesis / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000138:chemical synthesis*; D014771:Virion / Q000737:chemistry / Q000276:immunology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004337:Drug Carriers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022223:Vaccines, Subunit