Active immunization with bacteriophage AP205 VLPs results in reduced amyloid load and microgliosis in 5xFAD female mice

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dc.contributor.authorPilipenko, Vladimirs
dc.contributor.authorLieknina, Ilva
dc.contributor.authorSkrastina, Dace
dc.contributor.authorAktas, Selen
dc.contributor.authorRevina, Beatrise Luize
dc.contributor.authorUpite, Jolanta
dc.contributor.authorJansone, Baiba
dc.date.accessioned2026-04-04T13:37:35Z
dc.date.available2026-04-04T13:37:35Z
dc.date.issued2026
dc.departmentİnönü Üniversitesi
dc.description.abstractAlzheimer's disease (AD) is the leading cause of dementia worldwide and the accumulation of amyloid beta (A beta) oligomers in the brain parenchyma is one of the main characteristics of AD. Pyroglutamate-modified amyloid beta (pE3A beta) forms are highly pathogenic components of A beta plaques and are viable targets for disease-modifying strategies. Active immunization using virus-like particles (VLPs) represents a promising therapeutic approach to combating AD. Using RNA bacteriophage-based VLPs, we developed and tested a vaccine targeting pE3A beta in 5xFAD female mice. This study utilized the bacteriophage AP205 VLP platform to generate candidate compounds for active immunization. AP205 VLPs were modified to display short pE3A beta peptides. At 2 months of age, 5xFAD female mice received four immunizations with either pE3A beta VLPs or AP205 VLPs. Blood titers were assessed biweekly for the first 45 days and then every 2 months using ELISA. Behavioral tests, including open field, spontaneous alternation, Morris water maze, and elevated zero maze (EZM), were performed at 6 and 8 months of age. Immunohistochemical analyses evaluated levels of A beta 42, pE3A beta, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule-1 (Iba-1). pE3A beta VLPs and AP205 VLPs did not alter cognitive or locomotor performance in 5xFAD mice. The working memory of 8-month-old pE3A beta VLP-treated mice was better than it was at 6-months of age. A moderate reduction in A beta 42 pathology and microglial activation was observed in both vaccinated groups. VLP-based vaccine administration showed no behavioral improvements in 5xFAD mice but demonstrated modest effects on A beta 42 load and microgliosis.
dc.description.sponsorshipState Research Programme [VPP-EM-BIOMEDICINA-2022/1-0001]
dc.description.sponsorshipThis study was funded by the State Research Programme (project BioMedPharm nr. VPP-EM-BIOMEDICINA-2022/1-0001).
dc.identifier.doi10.1007/s00210-025-04739-y
dc.identifier.endpage4587
dc.identifier.issn0028-1298
dc.identifier.issn1432-1912
dc.identifier.issue3
dc.identifier.orcid0000-0002-7098-7483
dc.identifier.pmid41128902
dc.identifier.scopus2-s2.0-105019534180
dc.identifier.scopusqualityQ2
dc.identifier.startpage4569
dc.identifier.urihttps://doi.org/10.1007/s00210-025-04739-y
dc.identifier.urihttps://hdl.handle.net/11616/109915
dc.identifier.volume399
dc.identifier.wosWOS:001598762300001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofNaunyn-Schmiedebergs Archives of Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectPreclinical Alzheimer's disease
dc.subjectAlzheimer's vaccine
dc.subjectAnimal behavioral testing
dc.subjectVirus-like particles
dc.subjectTransgenic mice
dc.titleActive immunization with bacteriophage AP205 VLPs results in reduced amyloid load and microgliosis in 5xFAD female mice
dc.typeArticle

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