{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:54:18Z","timestamp":1785599658882,"version":"3.56.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>The burden of atherosclerotic cardiovascular disease contributes to a large proportion of morbidity and mortality, globally. Vaccination against atherosclerosis has been proposed for over 20 years targeting different mediators of atherothrombosis; however, these have not been adequately evaluated in human clinical trials to assess safety and efficacy. Inflammation is a driver of atherosclerosis, but inflammatory mediators are essential components of the immune response. Only pathogenic forms of sTNFR2 are acted upon while preserving the membrane-bound (wild-type) TNFR2 contributions to a non-pathogenic immune response. We hypothesize that the inhibition of sTNRF2 will be more specific and offer long-term treatment options. Here we describe pre-clinical findings of an sTNFR2-targeting peptide vaccine (AtheroVax\u2122) in a mouse model. The multiple pathways to synthesis of the soluble TNFRII receptor (sTNFRII) were identified as sTNFRII(PC), sTNFRII(\u03947), and sTNFRII(\u03947,9). The sTNFRII(\u03947) peptide, NH2-DFALPVEKPLCLQR-COOH is specific to sTNFR2 based on an mRNA splice-variant in which exon 6 is joined to exon 8. The role of sTNFRII(\u03947) as a mediator of prolonged TNF\u03b1 activity by preventing degradation and clearance was investigated. Inflammation is a critical driver of onset, progression and expansion of atherosclerosis. The TNF\u03b1 ligand represents a driver of inflammation that is mediated by a splice variant of TNFR2, referred to as sTNFRII(\u03947). The multiple forms of TNFRII, both membrane bound and soluble, are associated with distinctly different phenotypes. sTNFRII(PC) and sTNFRII(\u03947) are not equivalent to etanercept because they lack a clearance mechanism. The unique peptide associated with sTNFRII(\u03947) contains a linear B-cell epitope with amino acids from both exon 6 and exon 8 supporting the vaccine design. Animal studies to evaluate the vaccine are ongoing, and results will be forthcoming. We describe a peptide vaccine targeting sTNFR2 in limiting the progression of atherosclerosis. A therapeutic vaccine limiting the progression of atherosclerosis will greatly contribute to the reduction in morbidity and mortality from cardiovascular disease. It is likely the vaccine will be used in combination with the current standards of care and lifestyle modifications.<\/jats:p>","DOI":"10.3389\/fcvm.2023.1206541","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T10:08:43Z","timestamp":1689674923000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel therapeutic vaccine targeting the soluble TNF\u03b1 receptor II to limit the progression of cardiovascular disease: AtheroVax\u2122"],"prefix":"10.3389","volume":"10","author":[{"given":"Patrick L.","family":"Iversen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Kipshidze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nodar","family":"Kipshidze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dangas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Ramacciotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zurab","family":"Kakabadze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawed","family":"Fareed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s00228-021-03149-2","article-title":"A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCKS9","volume":"77","author":"Zeitlinger","year":"2021","journal-title":"Eur J Cliin Pharmacol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s12933-014-0151-6","article-title":"Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE an LDLR null mice","volume":"13","author":"Zhu","year":"2014","journal-title":"Cardiovasc Diabetol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1161\/CIRCULATIONAHA.121.057042","article-title":"Influenza vaccination after myocardial infarction","volume":"144","author":"Fr\u00f6bert","year":"2021","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/j.athoracsur.2020.07.052","article-title":"Influenza vaccination blunts the inflammatory response in patients undergoing cardiopulmonary bypass","volume":"111","author":"Atoui","year":"2021","journal-title":"Ann Thorac Surg"},{"key":"B5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.atherosclerosis.2011.03.019","article-title":"Influenza vaccination promotes stable atherosclerotic plaques in apoE knockout mice","volume":"217","author":"Bermudez-Fajardo","year":"2011","journal-title":"Atherosclerosis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"604","DOI":"10.3390\/nu10050604","article-title":"Inflammation, not cholesterol, is a cause of chronic disease","volume":"10","author":"Tsoupras","year":"2018","journal-title":"Nutrients"},{"key":"B7","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/S0092-8674(01)00237-9","article-title":"The TNF and TNF receptor superfamilies: integrating mammalian biology","volume":"104","author":"Locksley","year":"2001","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1084\/jem.128.6.1267","article-title":"Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. 3. Analysis of mechanism","volume":"128","author":"Ruddle","year":"1968","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3666","DOI":"10.1073\/pnas.72.9.3666","article-title":"An endotoxin-induced serum factor that causes necrosis of tumors","volume":"72","author":"Carswell","year":"1975","journal-title":"Proc Natl Acad Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1128\/iai.32.3.1058-1066.1981","article-title":"Possible importance of macrophage-derived mediators in acute malaria","volume":"32","author":"Clark","year":"1981","journal-title":"Infect Immun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3390\/biology11020157","article-title":"De novo optimized cell-free system for expression of soluble and active human tumor necrosis factor-alpha","volume":"11","author":"El-Baky","year":"2022","journal-title":"Biology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/jid.2008.332","article-title":"UVB and pro-inflammatory cytokines synergistically activate TNF-\u03b1 production in keratinocytes throughenhanced gene transcription","volume":"129","author":"Bashir","year":"2009","journal-title":"J Invest Dermatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e0167451","DOI":"10.1371\/journal.pone.0167451","article-title":"Tristetraprolin down-regulation contributes to persistent TNF-alpha expression induced by cigarette smoke extract through a post-transcriptional mechanism","volume":"11","author":"Zhao","year":"2016","journal-title":"PLoS One"},{"key":"B14","first-page":"1180","article-title":"Pharmacokinetics of tumor necrosis factor alpha after intravenous administration in rats. Dose dependence and influence of tumor necrosis factor beta","volume":"39","author":"Zahn","year":"1989","journal-title":"Arzneimittelforschung"},{"key":"B15","first-page":"358","article-title":"Pharmacokinetics of recombinant human tumor necrosis factor alpha in rhesus monkeys after intravenous administration","volume":"251","author":"Greischel","year":"1989","journal-title":"J Pharmacol Exp Ther"},{"key":"B16","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1073\/pnas.95.2.570","article-title":"The type I receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor","volume":"95","author":"Grell","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"B17","doi-asserted-by":"publisher","first-page":"564","DOI":"10.3390\/cancers13030564","article-title":"Harnessing tumor necrosis factor alpha to achieve effective cancer immunotherapy","volume":"13","author":"Mefcogliano","year":"2021","journal-title":"Cancers"},{"key":"B18","doi-asserted-by":"publisher","first-page":"4450162","DOI":"10.1155\/2021\/4450162","article-title":"Cost-effectiveness analysis of biopharmaceuticals for treating rheumatoid arthritis: infliximab, adalimumab, and etanercept","volume":"2021","author":"Gholame","year":"2021","journal-title":"BioMed Res International"},{"key":"B19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s13075-018-1646-4","article-title":"A randomized controlled trial comparing PF-06438179\/GP1111 (an infliximab biosimilar) and infliximab reference product for treatment of moderate to severe active rheumatoid arthritis despite methotrexate therapy","volume":"20","author":"Cohen","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1080\/19420862.2016.1216741","article-title":"The underlying inflammatory chronic disease influences infliximab pharmacokinetics","volume":"8","author":"Passot","year":"2016","journal-title":"MAbs"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e00733","DOI":"10.1002\/prp2.733","article-title":"Pharmacokinetics, safety, and immunogenicity of HLX03, an adalimumab biosimilar, compared with reference biologic in healthy Chinese male volunteers: results of a randomized, double-blind, parallel controlled, phase I study","volume":"9","author":"Zhang","year":"2021","journal-title":"Pharmacol Res Perspect"},{"key":"B22","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s13318-020-00613-9","article-title":"An open-label, randomized, single-dose, ccrossover, comparative pharmacokinetics study of YLB113 and the entanercept reference product in healthy adult malesubjects","volume":"45","author":"Shennak","year":"2020","journal-title":"Eur J Drug Met Pharmacokinet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/cts.12502","article-title":"A pilot dose-finding study of etanercept in rheumatoid arthritis","volume":"11","author":"Breedveld","year":"2018","journal-title":"Clin Transl Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0205125","DOI":"10.1371\/journal.pone.0205125","article-title":"Adherence to etanercept therapy in rheumatoid arthritis patients during 3 years of follow-up","volume":"13","author":"Vogelzang","year":"2018","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1586\/eci.10.69","article-title":"Certolizumab pegol: a new biologic targeting rheumatoid arthritis","volume":"6","author":"Patel","year":"2010","journal-title":"Expert Rev Clin Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"755844","DOI":"10.3389\/fimmu.2021.755844","article-title":"Toward overcoming treatment failure in rheumatoid arthritis","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/intimm\/dxu102","article-title":"Anti-TNF therapy: past, present and future","volume":"27","author":"Monaco","year":"2015","journal-title":"Int Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.atherosclerosis.2003.10.004","article-title":"Exclusive expression of transmembrane TNF-\u03b1 in mice reduces the inflammatory response in early lipid lesions of aortic stenosis","volume":"172","author":"Canault","year":"2004","journal-title":"Atherosclerosis"},{"key":"B29","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.ymgme.2008.11.166","article-title":"Tumor necrosis factor-alpha deficieny retards fatty-streak lesion by influencing expression of inflammatory factors in apoE-null mice","volume":"96","author":"Xiao","year":"2009","journal-title":"Mol Gener Metab"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/S0735-1097(02)01738-2","article-title":"Improved myocardial ischemia\/reperfusion injury in mice lacking tumor necrosis factor-\u03b1","volume":"39","author":"Maekawa","year":"2002","journal-title":"J Amm Coll Cardiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1128\/JVI.79.5.2659-2665.2005","article-title":"Roles of tumor necrosis factor alpha (TNF-\u03b1) and the p55 TNF receptor in CD1d induction and coxsackievirus B3-induced myocarditis","volume":"79","author":"Huber","year":"2005","journal-title":"J Virol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1161\/CIRCULATIONAHA.108.802918","article-title":"Divergent tumor necrosis factor-related remodeling responses in heart failure: role of nuclear factor-kappa B and inflammatory activation","volume":"119","author":"Hamid","year":"2009","journal-title":"Circulation"},{"key":"B33","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.arcmed.2016.11.006","article-title":"Association of G308A and G238A polymorphisms on the TNF-\u03b1 gene and risk of coronary heart disease: systemic review and meta-analysis","volume":"47","author":"Pulido-Gomez","year":"2016","journal-title":"Arch Med Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.3390\/ijms19071890","article-title":"Systemic inflammatory response and atherosclerosis: the paradigm of chronic inflammatory rheumatic diseases","volume":"19","author":"Arida","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1136\/annrheumdis-2016-209784","article-title":"Relationship between exposure to tumor necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis","volume":"76","author":"Low","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.ijcard.2018.06.099","article-title":"Anti-TNF modulation reduces myocardial inflammation and improves cardiovascular function in systemic rheumatoid diseases","volume":"270","author":"Ntusi","year":"2018","journal-title":"Int J Cardioll"},{"key":"B37","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1136\/ard.2006.062497","article-title":"Tumor necrosis factor-\u03b1 blockade, cardiovascular outcomes, and survival in rheumatoid arthritis","volume":"66","author":"Al-Aly","year":"2007","journal-title":"Ann Rheum Dis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.ahj.2008.02.025","article-title":"Tumor necrosis factor-\u03b1 antagonist use and heart failure in elderly patients with rheumatoid arthritis","volume":"156","author":"Setoguchi","year":"2008","journal-title":"Am Heart J"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1136\/annrheumdis-2012-202136","article-title":"Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonist","volume":"72","author":"Solomon","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"B40","doi-asserted-by":"publisher","first-page":"R1227","DOI":"10.1186\/ar1816","article-title":"Polymorphism in the tumor necrosis factor receptor II gene is associated with circulating levels of soluble tumor necrosis factor receptors in rheumatoid arthritis","volume":"7","author":"Glossop","year":"2005","journal-title":"Arthritis Res Ther"},{"key":"B41","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1080\/03009740701747137","article-title":"Soluble tumor necrosis factor receptors sTNFR1 and sTNFR2 are produced at sites of inflammation and are markers of arthritis activity in Behcet\u2019s disease","volume":"37","author":"Turan","year":"2008","journal-title":"Scand J Rheumatol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.2337\/diacare.28.6.1376","article-title":"A prospective study of soluble tumor necrosis factor-alpha receptor II (sTNFRII) and risk of coronary heart disease among women with type 2 diabetes","volume":"28","author":"Shai","year":"2005","journal-title":"Diabetes Care"},{"key":"B43","doi-asserted-by":"publisher","first-page":"207","DOI":"10.3389\/fphar.2018.00207","article-title":"Epigenome-wide association study of soluble tumor necrosis factor receptor 2 levels in the framingham heart study","volume":"9","author":"Mendelson","year":"2018","journal-title":"Front Pharmacol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e55477","DOI":"10.1371\/journal.pone.0055477","article-title":"Soluble TNF receptors are associated with infact size and ventricular dysfunction in ST-elevation myocardial infarction","volume":"8","author":"Nilsson","year":"2013","journal-title":"PLoS One"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e0122073","DOI":"10.1371\/journal.pone.0122073","article-title":"Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease: a prospective cohort study","volume":"10","author":"Neirynck","year":"2015","journal-title":"PLoS One"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e008299","DOI":"10.1161\/JAHA.117.008299","article-title":"10-Year associations between tumor necrosis factor receptors 1 and 2 and cardiovascular events in patients with stable coronary heart disease: a CLARICOR (effect of clarithromycin on mortality and morbidity in patients with ischemic heart disease) trial substudy","volume":"7","author":"Carlsson","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e0167757","DOI":"10.1371\/journal.pone.0167757","article-title":"Anti-TNF-\u03b1 drugs differentially affect the TNF-\u03b1-s TNFR system and monocyte subsets in patients with psoriasis","volume":"11","author":"Gibellini","year":"2016","journal-title":"PLoS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/intimm\/dxh014","article-title":"Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2","volume":"16","author":"Lainez","year":"2004","journal-title":"Int Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1038\/mt.2008.85","article-title":"An endogenous TNF-\u03b1 antagonist induced by splice-switching oligonucleotides reduces inflammation in hepatitis and arthritis mouse models","volume":"16","author":"Graziewicz","year":"2008","journal-title":"Mol Ther"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e1005271","DOI":"10.1371\/journal.ppat.1005271","article-title":"Tuberculosis in newborns: lessons of the \u201clubeck disaster\u201d (1929-1933)","volume":"12","author":"Fox","year":"2016","journal-title":"PLoS Pathog"},{"key":"B51","first-page":"261","article-title":"Bundaberg\u2019s gethsemane: the tragedy of the inoculated children","volume":"20","author":"Akers","year":"2008","journal-title":"Royal Historical Society Queensland J"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1001\/jama.1969.03150190037007","article-title":"Rheumatic fever following streptococcal vaccination. Report of three cases","volume":"207","author":"Massell","year":"1969","journal-title":"J Am Med Assoc"},{"key":"B53","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41541-023-00609-x","article-title":"The Streptococcus pyogenes vaccine landscape","volume":"8","author":"Walkinshaw","year":"2023","journal-title":"Npj Vaccines"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e00078","DOI":"10.1128\/MMBR.00078-20","article-title":"Subdominance in antibody responses: implications for vaccine development","volume":"85","author":"Lindahl","year":"2021","journal-title":"Microbiol Mol Biol Rev"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1038\/s41590-018-0210-3","article-title":"The immune responses against flaviviruses","volume":"19","author":"Slon Campos","year":"2018","journal-title":"Nat Immunol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.1128\/jvi.67.5.2552-2558.1993","article-title":"A commin neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains","volume":"67","author":"Okuno","year":"1993","journal-title":"J Virol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/S1074-7613(94)80017-0","article-title":"Development of high potency universal DR-restricted helper epitopes by modification of high affinity DR-blocking peptides","volume":"1","author":"Alexander","year":"1994","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","first-page":"869","DOI":"10.2147\/IJN.S269986","article-title":"Peptide-based nanovaccines in the treatment of cervical cancer: a review of recent advances","volume":"17","author":"Zhang","year":"2022","journal-title":"Int J Nanomed"},{"key":"B59","doi-asserted-by":"publisher","first-page":"19442","DOI":"10.1073\/pnas.0604827103","article-title":"TNFalpha kinoid vaccination-induced neutralizing antibodies to TNFalpha protect mice from autologous TNFalph-driven chronic and acute inflammation","volume":"103","author":"Le Buanec","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e113465","DOI":"10.1371\/journal.pone.0113465","article-title":"Therapeutic vaccination with TNF-kinoid in TNF antagonist-resistant rheumatoid arthritis: a phase II randomized, controlled clinical trial","volume":"9","author":"Durez","year":"2014","journal-title":"PLoS One"},{"key":"B61","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1039\/C5SC03892H","article-title":"Peptide-based synthetic vaccines","volume":"7","author":"Skwarczynski","year":"2016","journal-title":"Chem Sci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/nchem.2396","article-title":"Recent advances in the molecular design of synthetic vaccines","volume":"7","author":"Jones","year":"2015","journal-title":"Nat Chem"},{"key":"B63","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/0165-2478(95)00031-Y","article-title":"Epitope mapping of monoclonal antibodies to tumor necrosis factor-\u03b1","volume":"46","author":"Nagahira","year":"1995","journal-title":"Immunol Lett"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e0163080","DOI":"10.1371\/journal.pone.0163080","article-title":"Rationally designed TNF-\u03b1 epitope-scaffold immunogen induces sustained antibody response and alleviates collagen induced arthritis in mice","volume":"11","author":"Zhang","year":"2016","journal-title":"PLoS One"},{"key":"B65","doi-asserted-by":"publisher","first-page":"27171","DOI":"10.3390\/ijms161126017","article-title":"Abnormalities in alternative splicing of apoptotic genes and cardiovascular diseases","volume":"16","author":"Dlamini","year":"2015","journal-title":"Int J Mol Sci"},{"key":"B66","doi-asserted-by":"publisher","first-page":"35","DOI":"10.29245\/2578-3025\/2020\/1.1190","article-title":"Vaccination against atherosclerosis: a brief review and update","volume":"4","author":"Amirfakhryan","year":"2020","journal-title":"J Cardiol Cardiovasc Sci"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1206541\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T10:08:48Z","timestamp":1689674928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1206541\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,18]]},"references-count":66,"alternative-id":["10.3389\/fcvm.2023.1206541"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2023.1206541","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,18]]},"article-number":"1206541"}}