title: DNA immunization with HBsAg-based particles expressing a B cell epitope of amyloid β-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is an incurable and progressive neurodegenerative senile disorder associated with the brain accumulation of Aβ plaques. Although vaccines that reduce Aβ plaques can control AD, the rationale for their use at the onset of the disease remains debatable. Old humans and mice usually respond poorly to vaccines due to presumably age-related immunological impairments. Here, we report that by modifying vaccines, the poor responsiveness of old mice can be reversed. Unlike the Aβ peptide vaccine, DNA immunizations with the amino-terminal Aβ(1-11) fragment exposed on the surface of HBsAg particles elicit high levels of anti-Aβ antibody both in young and old mice. Importantly, in AD model 3xTgAD mice, the vaccine reduced Aβ plaques, ameliorated cognitive impairments and, surprisingly, significantly increased life span. Hence, we propose that vaccines targeting Aβ(1-11) can efficiently combat AD-induced pathological alterations and provide survival benefit in patients with AD.
authors.affiliation: Immunotherapeutics Section, Laboratory of Molecular Biology and Immunology, United States.
authors.forename: Purevdorj B
authors.initials: PB
authors.lastname: Olkhanud
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mughal
authors.forename: Koichi
authors.initials: K
authors.lastname: Ayukawa
authors.forename: Enkhzol
authors.initials: E
authors.lastname: Malchinkhuu
authors.forename: Monica
authors.initials: M
authors.lastname: Bodogai
authors.forename: Neil
authors.initials: N
authors.lastname: Feldman
authors.forename: Sarah
authors.initials: S
authors.lastname: Rothman
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Srinivasulu
authors.initials: S
authors.lastname: Chigurupati
authors.forename: Eitan
authors.initials: E
authors.lastname: Okun
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Arya
authors.initials: A
authors.lastname: Biragyn
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000276:immunology / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D018985:Epitopes, B-Lymphocyte; D006514:Hepatitis B Surface Antigens; D010446:Peptide Fragments; D019444:Vaccines, DNA; C115195:amyloid beta-protein (1-11)