Abstract
Poor adherence to secondary prevention in poststroke patients is one of the major causes for recurrence of ischemic stroke. Vaccination is a promising strategy for overcoming this limitation because of its long-term effects; however, it may have an increased risk of long-term side effects as well. Nevertheless, our recent studies reported that a vaccine against S100A9 and Ang II was effective without causing any major side effects. In this chapter, we present the history of vaccination for ischemic stroke and the possible use of antithrombotic and antihypertensive vaccines as secondary prevention measures in poststroke patients.
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References
Bane CE, Gailani D (2014) Factor XI as a target for antithrombotic therapy. Drug Discov Today 19:1454–1458. https://doi.org/10.1016/j.drudis.2014.05.018
Banks WA, Terrell B, Farr SA et al (2002) Passage of amyloid beta protein antibody across the blood-brain barrier in a mouse model of Alzheimer’s disease. Peptides 23:2223–2226
Becker KJ, McCarron RM, Ruetzler C et al (1997) Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia. Proc Natl Acad Sci U S A 94:10873–10878
Becker KJ, Kindrick DL, Lester MP et al (2005) Sensitization to brain antigens after stroke is augmented by lipopolysaccharide. J Cereb Blood Flow Metab 25:1634–1644. https://doi.org/10.1038/sj.jcbfm.9600160
Benicky J, Sánchez-Lemus E, Honda M et al (2011) Angiotensin II AT1 receptor blockade ameliorates brain inflammation. Neuropsychopharmacology 36:857–870. https://doi.org/10.1038/npp.2010.225
Büller HR, Bethune C, Bhanot S et al (2015) Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med 372:232–240. https://doi.org/10.1056/NEJMoa1405760
Bushnell CD, Olson DM, Zhao X et al (2011) Secondary preventive medication persistence and adherence 1 year after stroke. Neurology 77:1182–1190. https://doi.org/10.1212/WNL.0b013e31822f0423
Cai T-QQ, Wickham LA, Sitko G et al (2015) Platelet transfusion reverses bleeding evoked by triple anti-platelet therapy including vorapaxar, a novel platelet thrombin receptor antagonist. Eur J Pharmacol 758:107–114. https://doi.org/10.1016/j.ejphar.2015.03.073
Chen Z, Seiffert D, Hawes B (2014) Inhibition of factor XI activity as a promising antithrombotic strategy. Drug Discov Today 19:1435–1439. https://doi.org/10.1016/j.drudis.2014.04.018
Croce K, Gao H, Wang Y et al (2009) Myeloid-related protein-8/14 is critical for the biological response to vascular injury. Circulation 120:427–436. https://doi.org/10.1161/CIRCULATIONAHA.108.814582
Dirnagl U, Klehmet J, Braun JS et al (2007) Stroke-induced immunodepression. Stroke 38:770–773. https://doi.org/10.1161/01.STR.0000251441.89665.bc
Fu H, Hosomi N, Pelisch N et al (2011) Therapeutic effects of postischemic treatment with hypotensive doses of an angiotensin II receptor blocker on transient focal cerebral ischemia. J Hypertens 29:2210–2219. https://doi.org/10.1097/HJH.0b013e32834bbb30
Gailani D, Bane CE, Gruber A (2015) Factor XI and contact activation as targets for antithrombotic therapy. J Thromb Haemost 13:1383–1395. https://doi.org/10.1111/jth.13005
Garren H, Robinson WH, Krasulová E et al (2008) Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Ann Neurol 63:611–620. https://doi.org/10.1002/ana.21370
Garrido AM, Griendling KK (2009) NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol 302:148–158. https://doi.org/10.1016/j.mce.2008.11.003
Gasche Y, Copin JC, Chan PH (2001) The role of metalloproteinases on blood-brain barrier breakdown after ischemic stroke. In: Feuerstein GZ (ed) Inflammation and stroke. Springer, Basel, pp 265–274
Gee JM, Kalil A, Thullbery M, Becker KJ (2008) Induction of immunologic tolerance to myelin basic protein prevents central nervous system autoimmunity and improves outcome after stroke. Stroke 39:1575–1582. https://doi.org/10.1161/STROKEAHA.107.501486
Gee JM, Zierath D, Hadwin J et al (2009) Long term immunologic consequences of experimental stroke and mucosal tolerance. Exp Transl Stroke Med 1:3. https://doi.org/10.1186/2040-7378-1-3
Glader E-L, Sjölander M, Eriksson M, Lundberg M (2010) Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke. Stroke 41:397–401. https://doi.org/10.1161/STROKEAHA.109.566950
Goto S, Yamaguchi T, Ikeda Y et al (2010) Safety and exploratory efficacy of the novel thrombin receptor (PAR-1) antagonist SCH530348 for non-ST-segment elevation acute coronary syndrome. J Atheroscler Thromb 17(2):156–164
Hobbs JAR, May R, Tanousis K et al (2003) Myeloid cell function in MRP-14 (S100A9) null mice. Mol Cell Biol. https://doi.org/10.1128/MCB.23.7.2564-2576.2003
Horiuchi M, Mogi M (2011) Role of angiotensin II receptor subtype activation in cognitive function and ischaemic brain damage. Br J Pharmacol 163:1122–1130. https://doi.org/10.1111/j.1476-5381.2010.01167.x
Hosomi N, Nishiyama A, Matsumoto M (2013) Do RAS inhibitors protect the brain from cerebral ischemic injury? Curr Hypertens Rev 9. https://doi.org/10.2174/15734021113099990002
Iadecola C, Anrather J (2011) The immunology of stroke: from mechanisms to translation. Nat Med 17:796–808. https://doi.org/10.1038/nm.2399
Ito Y, Mitsufuji T, Yamamoto F et al (2011) Non-taking oral antithrombotic agents in patients with ischemic stroke. Rinsho Shinkeigaku 51:35–37
Jewell SD, Gienapp IE, Cox KL, Whitacre CC (1998) Oral tolerance as therapy for experimental autoimmune encephalomyelitis and multiple sclerosis: demonstration of T cell anergy. Immunol Cell Biol 76:74–82. https://doi.org/10.1046/j.1440-1711.1998.00716.x
Juryńczyk M, Walczak A, Jurewicz A et al (2010) Immune regulation of multiple sclerosis by transdermally applied myelin peptides. Ann Neurol 68:593–601. https://doi.org/10.1002/ana.22219
KA A, HL A (2003) Cellular and molecular immunology, 5th edn. Saunders, Philadelphia
Kawano T, Shimamura M, Nakagami H et al (2018) Therapeutic vaccine against S100A9 (S100 calcium-binding protein A9) inhibits thrombosis without increasing the risk of bleeding in ischemic stroke in mice. Hypertension 72:1355–1364. https://doi.org/10.1161/HYPERTENSIONAHA.118.11316
Koenig-Oberhuber V, Filipovic M (2016) New antiplatelet drugs and new oral anticoagulants. Br J Anaesth 117:ii74–ii84. https://doi.org/10.1093/bja/aew214
Kool M, Fierens K, Lambrecht BN (2012) Alum adjuvant: some of the tricks of the oldest adjuvant. J Med Microbiol 61:927–934. https://doi.org/10.1099/jmm.0.038943-0
Koriyama H, Nakagami H, Nakagami F et al (2015) Long-term reduction of high blood pressure by angiotensin II DNA vaccine in spontaneously hypertensive rats. Hypertension 66:167–174. https://doi.org/10.1161/HYPERTENSIONAHA.114.04534
Lee M, Saver JL, Hong K-S et al (2012) Renin-angiotensin system modulators modestly reduce vascular risk in persons with prior stroke. Stroke 43:113–119. https://doi.org/10.1161/STROKEAHA.111.632596
Merali Z, Huang K, Mikulis D et al (2017) Evolution of blood-brain-barrier permeability after acute ischemic stroke. PLoS One 12:e0171558. https://doi.org/10.1371/journal.pone.0171558
Morrow DA, Braunwald E, Bonaca MP et al (2012) Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 366:1404–1413. https://doi.org/10.1056/NEJMoa1200933
Nakagami F, Koriyama H, Nakagami H et al (2013a) Decrease in blood pressure and regression of cardiovascular complications by angiotensin II vaccine in mice. PLoS One 8(3):e60493. https://doi.org/10.1371/journal.pone.0060493
Nakagami F, Koriyama H, Nakagami H et al (2013b) Decrease in blood pressure and regression of cardiovascular complications by angiotensin II vaccine in mice. PLoS One 8:e60493. https://doi.org/10.1371/journal.pone.0060493
Ovbiagele B, Diener HC, Yusuf S et al (2011) Level of systolic blood pressure within the normal range and risk of recurrent stroke. JAMA 306:2137–2144. https://doi.org/10.1001/jama.2011.1650
Pang T, Wang J, Benicky J et al (2012) Telmisartan directly ameliorates the neuronal inflammatory response to IL-1β partly through the JNK/c-Jun and NADPH oxidase pathways. J Neuroinflammation. https://doi.org/10.1186/1742-2094-9-102
Powers WJ, Rabinstein AA, Ackerson T et al (2018) 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49:e46–e110. https://doi.org/10.1161/STR.0000000000000158
Pride M, Seubert P, Grundman M et al (2008) Progress in the active immunotherapeutic approach to Alzheimer’s disease: clinical investigations into AN1792-associated meningoencephalitis. Neurodegener Dis 5:194–196. https://doi.org/10.1159/000113700
Ravenni R, Jabre JF, Casiglia E, Mazza A (2011) Primary stroke prevention and hypertension treatment: which is the first-line strategy? Neurol Int 3:e12. https://doi.org/10.4081/ni.2011.e12
Saavedra JM (2012) Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders. Clin Sci (Lond) 123:567–590. https://doi.org/10.1042/CS20120078
Schiopu A, Cotoi OS (2013) S100A8 and S100A9: DAMPs at the crossroads between innate immunity, traditional risk factors, and cardiovascular disease. Mediat Inflamm 2013:828354. https://doi.org/10.1155/2013/828354
Shimamura M, Sato N, Morishita R (2011) Experimental and clinical application of plasmid DNA in the field of central nervous diseases. Curr Gene Ther 11:491–500
Shimamura M, Nakagami H, Sata M et al (2013) Unique remodeling processes after vascular injury in intracranial arteries: analysis using a novel mouse model. J Cereb Blood Flow Metab 33:1153–1159. https://doi.org/10.1038/jcbfm.2013.62
Tissot AC, Maurer P, Nussberger J et al (2008) Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet 371:821–827. https://doi.org/10.1016/S0140-6736(08)60381-5
Tricoci P, Huang Z, Held C et al (2012) Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 366:20–33. https://doi.org/10.1056/NEJMoa1109719
Wakayama K, Shimamura M, Suzuki J et al (2017) Angiotensin II peptide vaccine protects ischemic brain through reducing oxidative stress. Stroke 48:1362–1368. https://doi.org/10.1161/STROKEAHA.116.016269
Wang G, Sarkar P, Peterson JR et al (2013) COX-1-derived PGE 2 and PGE 2 type 1 receptors are vital for angiotensin II-induced formation of reactive oxygen species and ca 2+ influx in the subfornical organ. Am J Physiol Heart Circ Physiol 305:H1451–H1461. https://doi.org/10.1152/ajpheart.00238.2013
Wang Y, Fang C, Gao H et al (2014) Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis. J Clin Invest 124:2160–2171. https://doi.org/10.1172/JCI70966
Wekerle H, Kojima K, Lannes-Vieira J et al (1994) Animal models. Ann Neurol 36(Suppl):S47–S53
Willekens B, Cools N (2018) Beyond the magic bullet: current progress of therapeutic vaccination in multiple sclerosis. CNS Drugs 32:401–410. https://doi.org/10.1007/s40263-018-0518-4
Wu CY, Zha H, Xia QQ et al (2013) Expression of angiotensin II and its receptors in activated microglia in experimentally induced cerebral ischemia in the adult rats. Mol Cell Biochem 382:47–58. https://doi.org/10.1007/s11010-013-1717-4
Zhao HR, Jiang T, Tian YY et al (2015) Angiotensin II triggers apoptosis via enhancement of NADPH oxidase-dependent oxidative stress in a dopaminergic neuronal cell line. Neurochem Res 40:854–863. https://doi.org/10.1007/s11064-015-1536-y
Zhong C, Zhang L, Chen L et al (2017) Coagulation factor XI vaccination: an alternative strategy to prevent thrombosis. J Thromb Haemost 15:122–130. https://doi.org/10.1111/jth.13561
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The Department of Health Development and Medicine is financially supported by AnGes, DAICEL, and FunPep. The Department of Advanced Clinical Science and Therapeutics is financially supported by AnGes.
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Shimamura, M., Kawano, T., Wakayama, K., Nakagami, H. (2019). A Vaccine for Ischemic Stroke. In: Nakagami, H. (eds) Therapeutic Vaccines as Novel Immunotherapy. Springer, Singapore. https://doi.org/10.1007/978-981-32-9628-2_3
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