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Therapeutic Vaccines for Hypertension: a New Option for Clinical Practice

  • Resistant Hypertension (L Drager, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Vaccines are commonly used as preventive methods, primarily against infectious diseases. The goal of our study is to develop the therapeutic vaccine for hypertension.

Recent Findings

We and others recently reported that an angiotensin II (AngII) vaccine for hypertension successfully attenuated elevated blood pressures in an animal model without any immunogenic side effects. In this system, an immunogenic molecule (i.e., KLH) with adjuvants provides an antigen that supports the activation of helper T cells. In addition, pretreatment with the AngII vaccine exerts neuroprotective effects in a cerebral ischemia model and cardioprotective effects in a myocardial infarction model. In the early phase of clinical trial, the administration of an AngII vaccine (AngQb-Cyt006) successfully decreased blood pressure in hypertensive patients with the increase of anti-AngII antibody titer.

Summary

Increasing the effectiveness of drug adherence interventions in the clinical setting may have a large impact on the health of the population, which can be improved by using successful therapeutic vaccines. In this review, we describe the concept of therapeutic vaccines for hypertension and future directions for therapeutic vaccines.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Dyer MR, Renner WA, Bachmann MF. A second vaccine revolution for the new epidemics of the 21st century. Drug Discov Today. 2006;11(21–22):1028–33. https://doi.org/10.1016/j.drudis.2006.09.006.

    Article  PubMed  Google Scholar 

  2. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science. 2003;301(5638):1374–7. https://doi.org/10.1126/science.1086907.

    Article  CAS  PubMed  Google Scholar 

  3. Plescia OJ. The role of the carrier in antibody formation. Curr Top Microbiol Immunol. 1969;50:78–106.

    CAS  PubMed  Google Scholar 

  4. Paul S, Kenny AB, Hitzig WH. Immune response to keyhole-limpet hemocyanin in the human. Int Arch Allergy Appl Immunol. 1974;47(1):155–60. https://doi.org/10.1159/000231209.

    Article  CAS  PubMed  Google Scholar 

  5. Morgan D, Diamond DM, Gottschall PE, Ugen KE, Dickey C, Hardy J, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature. 2000;408(6815):982–5. https://doi.org/10.1038/35050116.

    Article  CAS  PubMed  Google Scholar 

  6. Nakagami F, Koriyama H, Nakagami H, Osako MK, Shimamura M, Kyutoku M, et al. Decrease in blood pressure and regression of cardiovascular complications by angiotensin II vaccine in mice. PLoS One. 2013;8(3):e60493. https://doi.org/10.1371/journal.pone.0060493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. • Wakayama K, Shimamura M, Suzuki JI, Watanabe R, Koriyama H, Akazawa H, et al. Angiotensin II peptide vaccine protects ischemic brain through reducing oxidative stress. Stroke. 2017;48(5):1362–8. Ang II vaccination exerts neuroprotective and antioxidative effects in cerebral ischemia in permanent middle cerebral artery occlusion model in rats, by penetration of anti-Ang II antibodies into ischemic brain lesion.

    Article  CAS  PubMed  Google Scholar 

  8. • Watanabe R, Suzuki JI, Wakayama K, Maejima Y, Shimamura M, Koriyama H, et al. A peptide vaccine targeting angiotensin II attenuates the cardiac dysfunction induced by myocardial infarction. Sci Rep. 2017;7:43920. Treatment with Ang II vaccine significantly suppressed post-myocardial infarction cardiac dysfunction in rats and Ang II-induced remodeling-associated signaling in cardiac fibroblasts.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wakerlin GE. Antibodies to renin as proof of the pathogenesis of sustained renal hypertension. Circulation. 1958;17(4):653–7. https://doi.org/10.1161/01.CIR.17.4.653.

    Article  CAS  PubMed  Google Scholar 

  10. Helmer OM. Studies on renin antibodies. Circulation. 1958;17(4):648–52. https://doi.org/10.1161/01.CIR.17.4.648.

    Article  CAS  PubMed  Google Scholar 

  11. Deodhar SD, Haas E, Goldblatt H. Production of antirenin to homologous renin and its effect of experimental renal hypertension. J Exp Med. 1964;119(3):425–32. https://doi.org/10.1084/jem.119.3.425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Michel JB, Guettier C, Philippe M, Galen FX, Corvol P, Menard J. Active immunization against renin in normotensive marmoset. Proc Natl Acad Sci U S A. 1987;84(12):4346–50. https://doi.org/10.1073/pnas.84.12.4346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Michel JB, Sayah S, Guettier C, Nussberger J, Philippe M, Gonzalez MF, et al. Physiological and immunopathological consequences of active immunization of spontaneously hypertensive and normotensive rats against murine renin. Circulation. 1990;81(6):1899–910. https://doi.org/10.1161/01.CIR.81.6.1899.

    Article  CAS  PubMed  Google Scholar 

  14. Gardiner SM, Auton TR, Downham MR, Sharp HL, Kemp PA, March JE, et al. Active immunization with angiotensin i peptide analogue vaccines selectively reduces the pressor effects of exogenous angiotensin i in conscious rats. Br J Pharmacol. 2000;129(6):1178–82. https://doi.org/10.1038/sj.bjp.0703178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ambuhl PM, Tissot AC, Fulurija A, Maurer P, Nussberger J, Sabat R, et al. A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase i safety and immunogenicity. J Hypertens. 2007;25(1):63–72. https://doi.org/10.1097/HJH.0b013e32800ff5d6.

    Article  PubMed  Google Scholar 

  16. Chen X, Qiu Z, Yang S, Ding D, Chen F, Zhou Y, et al. Effectiveness and safety of a therapeutic vaccine against angiotensin II receptor type 1 in hypertensive animals. Hypertension. 2013;61(1):408–16.

    Article  CAS  PubMed  Google Scholar 

  17. Azegami T, Sasamura H, Hayashi K, Itoh H. Vaccination against the angiotensin type 1 receptor for the prevention of L-NAME-induced nephropathy. Hypertens Res. 2012;35(5):492–9. https://doi.org/10.1038/hr.2011.212.

    Article  CAS  PubMed  Google Scholar 

  18. Brown MJ, Coltart J, Gunewardena K, Ritter JM, Auton TR, Glover JF. Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (pmd3117) in hypertensive subjects. Clin Sci (Lond). 2004;107(2):167–73. https://doi.org/10.1042/CS20030381.

    Article  CAS  Google Scholar 

  19. Tissot AC, Maurer P, Nussberger J, Sabat R, Pfister T, Ignatenko S, et al. Effect of immunisation against angiotensin ii with cyt006-angqb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet. 2008;371(9615):821–7. https://doi.org/10.1016/S0140-6736(08)60381-5.

    Article  CAS  PubMed  Google Scholar 

  20. Do TH, Chen Y, Nguyen VT, Phisitkul S. Vaccines in the management of hypertension. Expert Opin Biol Ther. 2010;10(7):1077–87.

    Article  CAS  PubMed  Google Scholar 

  21. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 2011;86(4):304–14. https://doi.org/10.4065/mcp.2010.0575.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was partly supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

  1. Department of Health Development and Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Hironori Nakagami

  2. Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Ryuichi Morishita

Authors
  1. Hironori Nakagami
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  2. Ryuichi Morishita
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Contributions

All of the authors contributed to writing the manuscript and have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Hironori Nakagami.

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Conflict of Interest

The Department of Health Development and Medicine was financially supported by Daicel, Mitsubishi-Tanabe, AnGes, and Funpep. The Department of Clinical Gene Therapy is financially supported by Novartis, AnGes, Shionogi, Boeringher, Fancl, Saisei Mirai Clinics, Rohto, and Funpep.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Resistant Hypertension

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Nakagami, H., Morishita, R. Therapeutic Vaccines for Hypertension: a New Option for Clinical Practice. Curr Hypertens Rep 20, 22 (2018). https://doi.org/10.1007/s11906-018-0820-z

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  • DOI: https://doi.org/10.1007/s11906-018-0820-z

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