Developing novel immunogens for an effective, safe Alzheimer's disease vaccine.
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.
Maier
Marcel
M
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Seabrook
Timothy J
TJ
Lemere
Cynthia A
CA
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
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000939:Epitopes