title: Developing novel immunogens for an effective, safe Alzheimer's disease vaccine.
abstract: Active amyloid beta (A beta) vaccination has been shown to be effective in clearing cerebral A beta and improving cognitive function in mouse models of Alzheimer's disease. However, an A beta vaccine clinical trial was suspended after meningoencephalitis was detected in a subset of subjects. Passive immunization has been suggested to be a safer alternative to active A beta immunization but there are reports of increased risk of microhemorrhages associated with its administration in aged beta-amyloid precursor protein transgenic mice bearing abundant vascular amyloid deposition. In addition, the cost may be prohibitive for large-scale clinical use. Therefore, we are designing novel A beta immunogens that encompass the B cell epitope of A beta but lack the T cell-reactive sites. These immunogens induced the production of A beta-specific antibodies in the absence of an A beta-specific cellular immune response in wild-type mice and are being tested in beta-amyloid precursor protein transgenic mice. These data together with published reports from several other groups suggest that a safe, active A beta vaccine is a tenable goal.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Maier
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Seabrook
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D002986:Clinical Trials as Topic; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D020080:Tandem Repeat Sequences
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000939:Epitopes