{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:05:07Z","timestamp":1790413507229,"version":"4.1.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["jlr.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Lipid Research"],"published-print":{"date-parts":[[2024,2]]},"DOI":"10.1016\/j.jlr.2024.100497","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T11:19:01Z","timestamp":1704885541000},"page":"100497","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":28,"title":["VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys"],"prefix":"10.1016","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7560-359X","authenticated-orcid":false,"given":"Madeline M.","family":"Vroom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett A.","family":"Thibodeaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne K.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Longo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8504-935X","authenticated-orcid":false,"given":"Martina M.","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-6084","authenticated-orcid":false,"given":"Jaya","family":"Sahni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Wiggins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D.","family":"Boyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hellerstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valorie","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Powchik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Cosme","family":"Dodart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jlr.2024.100497_bib1","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Abbafati","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.jlr.2024.100497_bib2","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1080\/00325481.2022.2117498","article-title":"LDL-C target attainment in secondary prevention of ASCVD in the United States: barriers, consequences of nonachievement, and strategies to reach goals","volume":"134","author":"Underberg","year":"2022","journal-title":"Postgrad. Med."},{"key":"10.1016\/j.jlr.2024.100497_bib3","doi-asserted-by":"crossref","first-page":"5770","DOI":"10.3390\/ijms22115770","article-title":"Antibody-based therapeutics for atherosclerosis and cardiovascular diseases","volume":"22","author":"Ji","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jlr.2024.100497_bib4","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2022.845942","article-title":"Foam cells in atherosclerosis: novel insights into its origins, consequences, and molecular mechanisms","volume":"9","author":"Gui","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.jlr.2024.100497_bib5","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.3390\/biomedicines9091221","article-title":"Macrophages and foam cells: brief overview of their role, linkage, and targeting potential in atherosclerosis","volume":"9","author":"Poznyak","year":"2021","journal-title":"Biomedicines"},{"key":"10.1016\/j.jlr.2024.100497_bib6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.5551\/jat.RV17030","article-title":"Diagnosis and management of statin intolerance","volume":"26","author":"Alonso","year":"2019","journal-title":"J.\u00a0Atheroscler. Thromb."},{"key":"10.1016\/j.jlr.2024.100497_bib7","article-title":"Adoption of pcsk9 inhibitors among patients with atherosclerotic disease","volume":"10","author":"Dayoub","year":"2021","journal-title":"J.\u00a0Am. Heart Assoc."},{"key":"10.1016\/j.jlr.2024.100497_bib8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.tibs.2006.12.008","article-title":"Molecular biology of PCSK9: its role in LDL metabolism","volume":"32","author":"Horton","year":"2007","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.jlr.2024.100497_bib9","article-title":"A\u00a0comprehensive review of PCSK9 inhibitors","volume":"27","author":"Coppinger","year":"2022","journal-title":"J.\u00a0Cardiovasc. Pharmacol. Ther."},{"key":"10.1016\/j.jlr.2024.100497_bib10","doi-asserted-by":"crossref","first-page":"5880","DOI":"10.3390\/ijms22115880","article-title":"Pcsk9 biology and its role in atherothrombosis","volume":"22","author":"Barale","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jlr.2024.100497_bib11","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1016\/S0140-6736(17)32290-0","article-title":"Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial","volume":"390","author":"Giugliano","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.jlr.2024.100497_bib12","first-page":"191","article-title":"Safety and tolerability of pcsk9 inhibitors: current insights","volume":"12","author":"Kosmas","year":"2020","journal-title":"Clin. Pharmacol."},{"key":"10.1016\/j.jlr.2024.100497_bib13","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/S2213-8587(17)30313-3","article-title":"Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial","volume":"5","author":"Sabatine","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"10.1016\/j.jlr.2024.100497_bib14","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and cardiovascular outcomes after acute coronary syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.jlr.2024.100497_bib15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s40273-015-0355-y","article-title":"PCSK9 inhibitors: a technology worth paying for?","volume":"34","author":"Weintraub","year":"2016","journal-title":"Pharmacoeconomics"},{"key":"10.1016\/j.jlr.2024.100497_bib16","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1080\/21645515.2018.1495301","article-title":"Immunology and efficacy of MF59-adjuvanted vaccines","volume":"14","author":"Ko","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"10.1016\/j.jlr.2024.100497_bib17","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/21645515.2015.1071455","article-title":"Safety and tolerability evaluation of the use of Montanide ISATM51 as vaccine adjuvant: a systematic review","volume":"12","author":"Van Doorn","year":"2016","journal-title":"Hum. Vaccin. Immunother."},{"key":"10.1016\/j.jlr.2024.100497_bib18","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1080\/21645515.2014.1004026","article-title":"Advances in aluminum hydroxide-based adjuvant research and its mechanism","volume":"11","author":"He","year":"2015","journal-title":"Hum. Vaccin. Immunother."},{"key":"10.1016\/j.jlr.2024.100497_bib19","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1002\/mds.29016","article-title":"A\u00a0randomized first-in-human study with UB-312, a UBITh\u00ae \u03b1-synuclein peptide vaccine","volume":"37","author":"Yu","year":"2022","journal-title":"Mov. Disord."},{"key":"10.1016\/j.jlr.2024.100497_bib20","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.trci.2017.03.005","article-title":"UB-311, a novel UBITh\u00ae amyloid \u03b2 peptide vaccine for mild Alzheimer\u2019s disease","volume":"3","author":"Wang","year":"2017","journal-title":"Alzheimers Dement. (N. Y.)"},{"key":"10.1016\/j.jlr.2024.100497_bib21","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1093\/gerona\/59.10.B1007","article-title":"Caloric restriction and cardiovascular aging in cynomolgus monkeys (Macaca fascicularis): metabolic, physiologic, and atherosclerotic measures from a 4-year intervention trial","volume":"59","author":"Cefalu","year":"2004","journal-title":"J.\u00a0Gerontol. A Biol. Sci. Med. Sci."},{"key":"10.1016\/j.jlr.2024.100497_bib22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1476-511X-13-11","article-title":"A\u00a0preliminary report on oral fat tolerance test in rhesus monkeys","volume":"13","author":"Wu","year":"2014","journal-title":"Lipids Health Dis."},{"key":"10.1016\/j.jlr.2024.100497_bib23","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/jcph.840","article-title":"Impact of target-mediated elimination on the dose and regimen of evolocumab, a human monoclonal antibody against proprotein convertase subtilisin\/kexin type 9 (PCSK9)","volume":"57","author":"Gibbs","year":"2017","journal-title":"J.\u00a0Clin. Pharmacol."},{"key":"10.1016\/j.jlr.2024.100497_bib24","doi-asserted-by":"crossref","first-page":"180","DOI":"10.18773\/austprescr.2016.078","article-title":"New drugs: evolocumab","volume":"39","year":"2016","journal-title":"Aust. Prescr."},{"key":"10.1016\/j.jlr.2024.100497_bib25","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3389\/fimmu.2014.00520","article-title":"IgG subclasses and allotypes: from structure to effector functions","volume":"5","author":"Vidarsson","year":"2014","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jlr.2024.100497_bib26","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/s41577-023-00871-z","article-title":"The unique properties of IgG4 and its roles in health and disease","volume":"23","author":"Rispens","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.jlr.2024.100497_bib27","doi-asserted-by":"crossref","first-page":"35513","DOI":"10.18632\/oncotarget.26275","article-title":"Designing consensus immunogens to break tolerance to self-antigens for cancer therapy","volume":"9","author":"Duperret","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.jlr.2024.100497_bib28","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s40119-020-00191-6","article-title":"Vaccines targeting PSCK9 for the treatment of hyperlipidemia","volume":"9","author":"Toth","year":"2020","journal-title":"Cardiol. Ther."},{"key":"10.1016\/j.jlr.2024.100497_bib29","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.immuni.2014.10.004","article-title":"T\u00a0follicular helper cell differentiation, function, and roles in disease","volume":"41","author":"Crotty","year":"2014","journal-title":"Immunity"},{"key":"10.1016\/j.jlr.2024.100497_bib30","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000442976","article-title":"Increased plasma PCSK9 levels are associated with reduced endotoxin clearance and the development of acute organ failures during sepsis","volume":"8","author":"Boyd","year":"2016","journal-title":"J.\u00a0Innate Immun."},{"key":"10.1016\/j.jlr.2024.100497_bib31","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.jacc.2021.07.056","article-title":"Hepatic sensing loop regulates PCSK9 secretion in response to inhibitory antibodies","volume":"78","author":"Oleaga","year":"2021","journal-title":"J.\u00a0Am. Coll. Cardiol."},{"key":"10.1016\/j.jlr.2024.100497_bib32","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s12872-022-02706-6","article-title":"Predictive value of LDL\/HDL ratio in coronary atherosclerotic heart disease","volume":"22","author":"Sun","year":"2022","journal-title":"BMC Cardiovasc. Disord."},{"key":"10.1016\/j.jlr.2024.100497_bib33","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1194\/jlr.M028340","article-title":"Immunization against proprotein convertase subtilisin-like\/kexin type 9 lowers plasma LDL-cholesterol levels in mice","volume":"53","author":"Fattori","year":"2012","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.jlr.2024.100497_bib34","article-title":"A\u00a0virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates","author":"Fowler","year":"2023","journal-title":"bioRxiv"},{"key":"10.1016\/j.jlr.2024.100497_bib35","doi-asserted-by":"crossref","first-page":"5747","DOI":"10.1016\/j.vaccine.2015.09.044","article-title":"A\u00a0cholesterol-lowering VLP vaccine that targets PCSK9","volume":"33","author":"Crossey","year":"2015","journal-title":"Vaccine"},{"key":"10.1016\/j.jlr.2024.100497_bib36","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-13069-w","article-title":"A\u00a0therapeutic peptide vaccine against PCSK9","volume":"7","author":"Pan","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jlr.2024.100497_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0114469","article-title":"Peptide-based anti-PCSK9 vaccines-an approach for long-term LDLc management","volume":"9","author":"Galabova","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jlr.2024.100497_bib38","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s00228-021-03149-2","article-title":"A\u00a0phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9","volume":"77","author":"Zeitlinger","year":"2021","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.jlr.2024.100497_bib39","series-title":"Current Indications, Cost, and Clinical Use of Anti-PCSK9 Monoclonal Antibodies","author":"Toklu","year":"2016"},{"key":"10.1016\/j.jlr.2024.100497_bib40","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s40265-016-0613-0","article-title":"Unmet needs in LDL-C lowering: when statins won\u2019t do!","volume":"76","author":"Kr\u00e4henb\u00fchl","year":"2016","journal-title":"Drugs"},{"key":"10.1016\/j.jlr.2024.100497_bib41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0090497","article-title":"The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model","volume":"9","author":"Hao","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jlr.2024.100497_bib42","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.jacl.2019.10.007","article-title":"Pharmacokinetic and pharmacodynamic assessment of alirocumab in patients with familial hypercholesterolemia associated with proprotein convertase subtilisin\/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations","volume":"13","author":"Hopkins","year":"2019","journal-title":"J.\u00a0Clin. Lipidol."},{"key":"10.1016\/j.jlr.2024.100497_bib43","first-page":"45","article-title":"Effect of evolocumab on lipoprotein(a) and PCSK9 in healthy individuals with elevated lipoprotein(a) level","volume":"7","author":"Afanasieva","year":"2020","journal-title":"J.\u00a0Cardiovasc. Dev. Dis."},{"key":"10.1016\/j.jlr.2024.100497_bib44","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/cmi.2010.22","article-title":"The cytokine milieu in the interplay of pathogenic Th1\/Th17 cells and regulatory T cells in autoimmune disease","volume":"7","author":"Leung","year":"2010","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.jlr.2024.100497_bib45","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.intimp.2013.08.012","article-title":"A\u00a0critical role for interleukin-1\u03b2 in the progression of autoimmune diseases","volume":"17","author":"Zhao","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.jlr.2024.100497_bib46","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a016295","article-title":"Il-6 in inflammation, immunity, and disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.jlr.2024.100497_bib47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00401-021-02381-5","article-title":"Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric \u03b1-synuclein accumulation in the brain and gut","volume":"143","author":"Nimmo","year":"2022","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.jlr.2024.100497_bib48","first-page":"406","article-title":"Mechanism of immunopotentiation and safety of aluminum adjuvants","volume":"3","author":"HogenEsch","year":"2012","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jlr.2024.100497_bib49","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.dmpk.2018.02.003","article-title":"Importance of cynomolgus monkeys in development of monoclonal antibody drugs","volume":"34","author":"Iwasaki","year":"2019","journal-title":"Drug Metab. Pharmacokinet."}],"container-title":["Journal of Lipid Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227524000026?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227524000026?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T18:34:28Z","timestamp":1758306868000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022227524000026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["S0022227524000026"],"URL":"https:\/\/doi.org\/10.1016\/j.jlr.2024.100497","relation":{},"ISSN":["0022-2275"],"issn-type":[{"value":"0022-2275","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys","name":"articletitle","label":"Article Title"},{"value":"Journal of Lipid Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jlr.2024.100497","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"100497"}}