{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:54:19Z","timestamp":1787849659688,"version":"build-2784847793"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pyroglutamate amyloid beta3\u201342 (pGlu-Abeta3\u201342), a highly amyloidogenic and neurotoxic form of Abeta, is N-terminally truncated to form a pyroglutamate and has recently been proposed as a key target for immunotherapy. Optimized ACI-24, a vaccine in development for the treatment and prevention of Alzheimer\u2019s disease, focuses the antibody response on the first 15 N-terminal amino acids of Abeta (Abeta1\u201315). Importantly, clinical data with an initial version of ACI-24 incorporating Abeta1\u201315, established the vaccine\u2019s safety and tolerability with evidence of immunogenicity. To explore optimized ACI-24\u2019s capacity to generate antibodies to pGlu-Abeta3\u201342, pre-clinical studies were carried out. Vaccinating mice and non-human primates demonstrated that optimized ACI-24 was well-tolerated and induced an antibody response against Abeta1\u201342 as expected, as well as high titres of IgG reactive with pyroGlu-Abeta. Epitope mapping of the polyclonal response confirmed these findings revealing broad coverage of epitopes particularly for Abeta peptides mimicking where cleavage occurs to form pGlu-Abeta3\u201342. These data are in striking contrast to results obtained with other clinically tested Abeta targeting vaccines which generated restricted and limited antibody diversity. Taken together, our findings demonstrate that optimized ACI-24 vaccination represents a breakthrough to provide a safe immune response with a broader Abeta sequence recognition compared to previously tested vaccines, creating binders to pathogenic forms of Abeta important in pathogenesis including pGlu-Abeta3\u201342.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac022","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T12:18:34Z","timestamp":1643717914000},"source":"Crossref","is-referenced-by-count":24,"title":["An amyloid beta vaccine that safely drives immunity to a key pathological species in Alzheimer\u2019s disease: pyroglutamate amyloid beta"],"prefix":"10.1093","volume":"4","author":[{"given":"M.","family":"Vukicevic","sequence":"first","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Fiorini","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9827-4282","authenticated-orcid":false,"given":"S.","family":"Siegert","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Carpintero","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rincon-Restrepo","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Lopez-Deber","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Piot","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ayer","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Rentero","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Babolin","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bravo-Veyrat","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Giriens","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Morici","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Beuzelin","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Gesbert","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Rivot","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Depretti","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Donati","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Streffer","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"},{"name":"Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"AC Immune SA, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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