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These experimental therapies generate antibodies that have demonstrated binding to pathological tau in vitro, and efficacy in cell\u2010based tau aggregation assays comparable to monoclonal antibodies. Here, we report the ability of one such tau\u2010targeting immunotherapy, p5555kb, to prevent the progression of tau pathology using two distinct mouse models. P301L mice were immunized with p5555kb and showed greater survival rates at 210\u2009days than saline\u2010inoculated control mice. The efficacy of p5555kb against tau seeding in vivo was assessed by injecting C57BL6 mice with tau fibrils purified from post\u2010mortem human AD brain tissue. Immunization with p5555kb significantly reduced the amount of tau inclusions detected by immunohistochemistry at 9\u2009months post\u2010injection, as compared to saline inoculation. This study demonstrates that p5555kb is effective at inducing functional tau\u2010targeting antibodies, which prevented the onset of adverse phenotypes associated with tau pathology in vitro and in vivo.<\/jats:p>","DOI":"10.1111\/bpa.70056","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:09:08Z","timestamp":1764893348000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tau\u2010targeting active immunotherapy slows progression and reduces pathology in mouse models of tauopathy"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1569-3132","authenticated-orcid":false,"given":"Christopher M.","family":"Brown","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Southampton General Hospital University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne K.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Vaxxinity  Merritt Island Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Kelly","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Southampton General Hospital University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline M.","family":"Vroom","sequence":"additional","affiliation":[{"name":"Vaxxinity  Merritt Island Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Longo","sequence":"additional","affiliation":[{"name":"Vaxxinity  Merritt Island Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Cosme","family":"Dodart","sequence":"additional","affiliation":[{"name":"Vaxxinity  Merritt Island Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana","family":"Carare","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Southampton General Hospital University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin D.","family":"Boyd","sequence":"additional","affiliation":[{"name":"Vaxxinity  Merritt Island Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01146-y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-12679-1_1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.09.001"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000063311.58879.01"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2361-07.2007"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-017-0298-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061516-045049"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.11.026"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0146127"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057116638029"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-016-0100-9"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010532"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116132"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz100"},{"key":"e_1_2_11_17_1","unstructured":"SokollKK.Stabilized synthetic immunogen delivery system. 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