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One of the hallmarks of Alzheimer\u2019s disease is the high levels of tau protein, which can form toxic oligomers and characteristic neurofibrillary tangles in the brain. Antitau antibodies can potentially bind tau protein and reduce tau pathology. In order to elicit a powerful antitau antibody response, virus-like-particle bacteriophage Q\u03b2-based conjugate vaccines were developed targeting the microtubule binding region of tau protein. The Q\u03b2-tau vaccines were able to produce a strong antitau antibody response in not only wild-type mice but also in human tau transgenic mice and a llama. The levels of antibody induced were superior to those generated by a corresponding keyhole limpet hemocyanin-based tau conjugate mimicking the one vaccine that successfully completed phase 1\/2 human clinical trials. The Q\u03b2-tau vaccine significantly improved the cognitive functions of the immunized mice and reduced the levels of inflammatory cytokines and tau in the brains, suggesting its translational potential.<\/jats:p>","DOI":"10.1021\/acsomega.6c00852","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:11:43Z","timestamp":1784124703000},"page":"43242-43254","source":"Crossref","is-referenced-by-count":0,"title":["A Virus-Like-Particle-Based\nConjugate Vaccine Targeting\nthe Microtubule Binding Region of Tau Protein"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9870-4326","authenticated-orcid":true,"given":"Hunter","family":"McFall-Boegeman","sequence":"first","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Talbot","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0456-452X","authenticated-orcid":true,"given":"Mauro","family":"Montalbano","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch , , , ,","place":["Galveston, Texas, United States, 77555"]},{"name":"University of Texas Medical Branch , , , ,","place":["Galveston, Texas, United States, 77555"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicha","family":"Puangmalai","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch , , , ,","place":["Galveston, Texas, United States, 77555"]},{"name":"University of Texas Medical Branch , , , ,","place":["Galveston, Texas, United States, 77555"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Kannan","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Shi","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Linning-Duffy","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Setare","family":"Nick","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Yan","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hao","family":"Kuo","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6216-8640","authenticated-orcid":true,"given":"Rakez","family":"Kayed","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch , , , ,","place":["Galveston, Texas, United States, 77555"]},{"name":"University of Texas Medical Branch , , , ,","place":["Galveston, Texas, United States, 77555"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6468-5526","authenticated-orcid":true,"given":"Xuefei","family":"Huang","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"2026072810080943000_cit1","unstructured":"Alzheimer\u2019s Association.\n          . 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Chem."},{"key":"2026072810080943000_cit6","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00083","article-title":"The Importance\nof Tau Phosphorylation for Neurodegenerative Diseases","volume":"4","author":"Noble","year":"2013","journal-title":"Front. Neurol."},{"key":"2026072810080943000_cit7","doi-asserted-by":"publisher","first-page":"10047","DOI":"10.1021\/bi901090m","article-title":"Conformational\nChanges Specific for Pseudophosphorylation at Serine 262 Selectively\nImpair Binding of Tau to Microtubules","volume":"48","author":"Fischer","year":"2009","journal-title":"Biochemistry"},{"key":"2026072810080943000_cit8","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1046\/j.1471-4159.2003.02287.x","article-title":"Pseudophosphorylation\nof tau protein alters its ability for self-aggregation","volume":"88","author":"Haase","year":"2004","journal-title":"J. Neurochem."},{"key":"2026072810080943000_cit9","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00114","article-title":"Are Tau Aggregates\nToxic or Protective in Tauopathies?","volume":"4","author":"Cowan","year":"2013","journal-title":"Front.\nNeurol."},{"key":"2026072810080943000_cit10","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00083","article-title":"Tau Oligomers:\nCytotoxicity, Propagation, and Mitochondrial Damage","volume":"9","author":"Shafiei","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"2026072810080943000_cit11","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-6-39","article-title":"Tau Oligomers\nImpair Memory and Induce Synaptic and Mitochondrial\nDysfunction in Wild-Type Mice","volume":"6","author":"Lasagna-Reeves","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"2026072810080943000_cit12","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt277","article-title":"Identification\nof Structural Determinants on Tau Protein Essential for its Pathological\nFunction: Novel Therapeutic Target for Tau Immunotherapy in Alzheimer\u2019s\nDisease","volume":"6","author":"Kontsekova","year":"2014","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"2026072810080943000_cit13","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/acn3.176","article-title":"Anti-tau antibody reduces insoluble\ntau and decreases brain atrophy","volume":"2","author":"Yanamandra","year":"2015","journal-title":"Ann. Clin.\nTransl. Neurol."},{"key":"2026072810080943000_cit14","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adj5958","article-title":"Nasal tau immunotherapy clears intracellular tau pathology and improves\ncognitive functions in aged tauopathy mice","volume":"16","author":"Gaikwad","year":"2024","journal-title":"Sci. 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Ed."},{"key":"2026072810080943000_cit37","doi-asserted-by":"publisher","first-page":"24179","DOI":"10.1002\/anie.202108610","article-title":"Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic\nInstability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development","volume":"60","author":"Wu","year":"2021","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026072810080943000_cit38","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1021\/acschembio.1c00906","article-title":"Structure Guided Design of the Bacteriophage Q\u03b2 Mutants as\nNext Generation Carriers for Conjugate Vaccines","volume":"17","author":"Sungsuwan","year":"2022","journal-title":"ACS. Chem. Biol."},{"key":"2026072810080943000_cit39","doi-asserted-by":"publisher","DOI":"10.1038\/srep00700","article-title":"Alzheimer\nbrain-derived tau oligomers propagate pathology from endogenous tau","volume":"2","author":"Lasagna-Reeves","year":"2012","journal-title":"Sci. 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Neurobiol."},{"key":"2026072810080943000_cit43","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.bbrc.2007.04.187","article-title":"Epitope mapping\nof mAbs AT8 and Tau5\ndirected against hyperphosphorylated regions of the human tau protein","volume":"358","author":"Porzig","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026072810080943000_cit44","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.4049\/jimmunol.142.8.2635","article-title":"Carrier-induced epitopic\nsuppression is initiated through clonal dominance","volume":"142","author":"Schutze","year":"1989","journal-title":"J. Immunol."},{"key":"2026072810080943000_cit45","doi-asserted-by":"publisher","first-page":"5503","DOI":"10.1016\/j.vaccine.2010.02.103","article-title":"Carrier\ninduced epitopic suppression\nof antibody responses induced by virus-like particles is a dynamic\nphenomenon caused by carrier-specific antibodies","volume":"28","author":"Jegerlehner","year":"2010","journal-title":"Vaccine."},{"key":"2026072810080943000_cit46","doi-asserted-by":"publisher","first-page":"184","DOI":"10.3109\/08923973.2016.1165246","article-title":"The effect of preexisting anti-carrier immunity on\nsubsequent responses to CRM197 or Qb-VLP conjugate vaccines","volume":"38","author":"McCluskie","year":"2016","journal-title":"Immunopharmacol. 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Aging."},{"key":"2026072810080943000_cit50","doi-asserted-by":"publisher","first-page":"55718","DOI":"10.3791\/55718","article-title":"Novel Object\nRecognition Test for the Investigation of Learning and Memory in Mice","author":"Lueptow","year":"2017","journal-title":"J. Vis. Exp."},{"key":"2026072810080943000_cit51","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41105-4","article-title":"Antibody-mediated\nclearance of tau in primary mouse microglial cultures requires Fc\u03b3-receptor\nbinding and functional lysosomes","volume":"9","author":"Andersson","year":"2019","journal-title":"Sci. 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