A pentavalent peptide vaccine elicits Aβ and tau antibodies with prophylactic activity in an Alzheimer's disease mouse model.

Autor: Song Y; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Dai CL; Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA., Shinohara M; Department of Aging Neurobiology, Research Institute, National Center for Geriatrics and Gerontology, 7-430, Morioka, Obu, Aichi 474-8511, Japan., Chyn Tung Y; Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA., Zhou S; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Huang WC; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA; POP Biotechnologies, Buffalo, NY 14228, USA., Seffouh A; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 0C7, Canada., Luo Y; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Willadsen M; POP Biotechnologies, Buffalo, NY 14228, USA., Jiao Y; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Morishima M; Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2, Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan., Saito Y; Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2, Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan., Koh SH; Department of Neurology, Hanyang University Guri Hospital, Guri-si, Gyeonggi-do 11923, Republic of Korea., Ortega J; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 0C7, Canada., Gong CX; Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. Electronic address: Chengxin.Gong@csi.cuny.edu., Lovell JF; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA. Electronic address: jflovell@buffalo.edu.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Nov; Vol. 122, pp. 185-201. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1016/j.bbi.2024.08.028
Abstrakt: Amyloid-β (Aβ) and hyperphosphorylated tau protein are targets for Alzheimer's Disease (AD) immunotherapies, which are generally focused on single epitopes within Aβ or tau. However, due to the complexity of both Aβ and tau in AD pathogenesis, a multipronged approach simultaneously targeting multiple epitopes of both proteins could overcome limitations of monotherapies. Herein, we propose an active AD immunotherapy based on a nanoparticle vaccine comprising two Aβ peptides (1-14 and pyroglutamate pE3-14) and three tau peptides (centered on phosphorylated pT181, pT217 and pS396/404). These correspond to both soluble and aggregated targets and are displayed on the surface of immunogenic liposomes in an orientation that maintains reactivity with epitope-specific monoclonal antibodies. Intramuscular immunization of mice with individual epitopes resulted in minimally cross-reactive antibody induction, while simultaneous co-display of 5 antigens ("5-plex") induced antibodies against all epitopes without immune interference. Post-immune sera recognized plaques and neurofibrillary tangles from human AD brain tissue. Vaccine administration to 3xTg-AD mice using a prophylactic dosing schedule inhibited tau and amyloid pathologies and resulted in improved cognitive function. Immunization was well tolerated and did not induce antigen-specific cellular responses or persistent inflammatory responses in the peripheral or central nervous system. Antibody levels could be reversed by halting monthly vaccinations. Altogether, these results indicate that active immune therapies based on nanoparticle formulations of multiple Aβ and tau epitopes warrant further study for treating early-stage AD.
Competing Interests: Declaration of Competing Interest J.F.L. and W-C.H. hold interest in POP Biotechnologies. W-C.H. and M.W. are employees of POP Biotechnologies. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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