Skip to main content

Advertisement

SpringerLink
Log in

Vaccination for Atherosclerosis

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Atherosclerosis is an inflammatory disease, and several antigens have been shown to activate the immune response and affect the development of atherogenesis. This suggests that modulation of the immune system could represent a useful approach to prevent and/or treat this disorder. A vaccination approach might be a useful, effective tool in the modern arsenal of cardiovascular therapy and could possibly be used on a large scale at a low cost. Several modalities of vaccines have been tested against lipoproteins, cholesterol, molecules involved in cholesterol metabolism, atherosclerosis-associated microorganisms, and other molecules (heat shock protein, CD99, vascular endothelial growth factor-receptor, interleukin-2), with promising results. Nevertheless, a deeper understanding of the role of immunization in atherosclerosis will be essential to the use of vaccines in clinical medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jara LJ, Medina G, Vera-Lastra O, Amigo MC (2006) Accelerated atherosclerosis, immune response and autoimmune rheumatic diseases. Autoimmun Rev 5:195–201

    Article  PubMed  Google Scholar 

  2. Sherer Y, Shoenfeld Y (2002) Atherosclerosis. Ann Rheum Dis 61:97–99

    Article  CAS  PubMed  Google Scholar 

  3. Kannel WB, Castelli WP, Gordon T (1979) Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Ann Intern Med 90:85–91

    CAS  PubMed  Google Scholar 

  4. Asztalos BF, Schaefer EJ (2003) HDL in atherosclerosis: actor or bystander? Atheroscler Suppl 4:21–29

    Article  CAS  PubMed  Google Scholar 

  5. Su J, Georgiades A, Wu R, Thulin T, de Faire U, Frostegård J (2006) Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension. Atherosclerosis 188:160–166

    Article  CAS  PubMed  Google Scholar 

  6. Frostegård J, Tao W, Georgiades A, Råstam L, Lindblad U, Lindeberg S (2007) Atheroprotective natural anti-phosphorylcholine antibodies of IgM subclass are decreased in Swedish controls as compared to non-westernized individuals from New Guinea. Nutr Metab (Lond) 4:7

    Article  Google Scholar 

  7. Elkan AC, Sjöberg B, Kolsrud B, Ringertz B, Hafström I, Frostegård J (2008) Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study. Arthritis Res Ther 10:R34

    Article  PubMed  Google Scholar 

  8. Su J, Hua X, Concha H, Svenungsson E, Cederholm A, Frostegård J (2008) Natural antibodies against phosphorylcholine as potential protective factors in SLE. Rheumatology (Oxford) 47:1144–1150

    Article  CAS  Google Scholar 

  9. Rajaiah R, Moudgil KD (2009) Heat-shock proteins can promote as well as regulate autoimmunity. Autoimmun Rev 8:388–393

    Article  CAS  PubMed  Google Scholar 

  10. Okada T, Ayada K, Usui S, Yokota K, Cui J, Kawahara Y et al (2007) Antibodies against heat shock protein 60 derived from Helicobacter pylori: diagnostic implications in cardiovascular disease. J Autoimmun 29:106–115

    Article  CAS  PubMed  Google Scholar 

  11. Shoenfeld Y, Selmi C, Zimlichman E, Gershwin ME (2008) The autoimmunologist: geoepidemiology, a new center of gravity, and prime time for autoimmunity. J Autoimmun 31:325–330

    Article  PubMed  Google Scholar 

  12. Conti F, Rezai S, Valesini G (2008) Vaccination and autoimmune rheumatic diseases. Autoimmun Rev 8:124–128

    Article  CAS  PubMed  Google Scholar 

  13. Tsonis IA, Avrameas S, Moutsopoulos HM (2007) Autoimmunity and pathophysiology. J Autoimmun. 29:203–205

    Article  CAS  PubMed  Google Scholar 

  14. Gero S, Gergely J, Jakab L, Szekely J, Virag S, Farkas K, Czuppon A (1959) Inhibition of cholesterol atherosclerosis by immunisation with beta-lipoprotein. Lancet 2:6–7

    Article  CAS  PubMed  Google Scholar 

  15. Gero S (1967) Some data on the influence of cholesterol atherosclerosis by immunological means. Rev Atheroscler (Paris) 9(Suppl 1):194–198

    Google Scholar 

  16. Siegler PE (1967) Some immunological aspects of atherosclerosis. Rev Atheroscler (Paris) 9(Suppl 1):199

    Google Scholar 

  17. Bailey Jm, Tomar R (1965) Lipoprotein immunization and induced atherosclerosis in rabbits. 1. Cockerel beta-lipoproteins as antigens. J Atheroscler Res 5:203–214

    Article  CAS  PubMed  Google Scholar 

  18. Palinski W, Tangirala RK, Miller E, Young SG, Witztum JL (1995) Increased autoantibody titers against epitopes of oxidized LDL in LDL receptor-deficient mice with increased atherosclerosis. Arterioscler Thromb Vasc Biol 15:1569–1576

    CAS  PubMed  Google Scholar 

  19. Ameli S, Hultgårdh-Nilsson A, Regnström J, Calara F, Yano J, Cercek B et al (1996) Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits. Arterioscler Thromb Vasc Biol 16:1074–1079

    CAS  PubMed  Google Scholar 

  20. Fredrikson GN, Soderberg I, Lindholm M, Dimayuga P, Chyu KY, Shah PK, Nilsson J (2003) Inhibition of atherosclerosis in apoE-null mice by immunization with apoB-100 peptide sequences. Arterioscler Thromb Vasc Biol 23:879–884

    Article  CAS  PubMed  Google Scholar 

  21. Bailey JM, Bright R, Tomar R (1964) Immunization with a synthetic cholesterol-ester antigen and induced atherosclerosis in rabbits. Nature 201:407–408

    Article  CAS  PubMed  Google Scholar 

  22. Bailey JM, Bright R, Tomar R, Butler J (1994) Anti-atherogenic effects of cholesterol vaccination. Biochem Soc Trans 22:433S

    CAS  PubMed  Google Scholar 

  23. Alving CR, Swartz GM Jr, Wassef NM, Ribas JL, Herderick EE, Virmani R et al (1996) Immunization with cholesterol-rich liposomes induces anti-cholesterol antibodies and reduces diet-induced hypercholesterolemia and plaque formation. J Lab Clin Med 127:40–49

    Article  CAS  PubMed  Google Scholar 

  24. Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (2003) Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 23:160–167

    Article  CAS  PubMed  Google Scholar 

  25. Rittershaus CW, Miller DP, Thomas LJ, Picard MD, Honan CM, Emmett CD et al (2000) Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis. Arterioscler Thromb Vasc Biol 20:2106–2112

    CAS  PubMed  Google Scholar 

  26. Davidson MH, Maki K, Umporowicz D, Wheeler A, Rittershaus C, Ryan U (2003) The safety and immunogenicity of a CETP vaccine in healthy adults. Atherosclerosis 169:113–120

    Article  CAS  PubMed  Google Scholar 

  27. Ryan US, Rittershaus CW (2006) Vaccines for the prevention of cardiovascular disease. Vascul Pharmacol 45:253–257

    Article  CAS  PubMed  Google Scholar 

  28. Rittershaus CW (2007) Vaccines for cholesterol management. World J Surg 31:690–694

    Article  PubMed  Google Scholar 

  29. Gaofu Q, Rongyue C, Dan M, Xiuyun Z, Xuejun W, Jie W et al (2006) Asparaginase display of human cholesteryl ester transfer protein (CETP) B cell epitopes for inducing high titers of anti-CETP antibodies in vivo. Prot Peptide Letters 13:149–154

    Article  Google Scholar 

  30. Gaofu Q, Jun L, Xiuyun Z, Wentao L, Jie W, Jingjing L (2005) Antibody against cholesteryl ester transfer protein (CETP) elicited by a recombinant chimeric enzyme vaccine attenuated atherosclerosis in a rabbit model. Life Sci 77:2690–2702

    Article  PubMed  Google Scholar 

  31. Gaofu Q, Jun L, Xin Y, Wentao L, Jie W, Xiuyun Z et al (2005) Vaccinating rabbits with a cholesteryl ester transfer protein (CETP) B-Cell epitope carried by heat shock protein-65 (HSP65) for inducing anti-CETP antibodies and reducing aortic lesions in vivo. J Cardiovasc Pharmacol 45:591–598

    Article  PubMed  Google Scholar 

  32. Gaofu Q, Dan M, Jie W, Liao Z, Li Z, Roque RS, Jingjing L (2004) Long-lasting specific antibodies against CETP induced by subcutaneous and mucosal administration of a 26-amino acid CETP epitope carried by heat shock protein 65 kDa in the absence of adjuvants. Vaccine 22:3187–3194

    Article  CAS  PubMed  Google Scholar 

  33. Lamb DJ, El-Sankary W, Ferns GA (2003) Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. Atherosclerosis 167:177–185

    Article  CAS  PubMed  Google Scholar 

  34. Alard JE, Dueymes M, Youinou P, Jamin C (2007) Modulation of endothelial cell damages by anti-Hsp60 autoantibodies in systemic autoimmune diseases. Autoimmun Rev 6:438–443

    Article  CAS  PubMed  Google Scholar 

  35. Bassi N, Ghirardello A, Iaccarino L, Zampieri S, Rampudda ME, Atzeni F, Sarzi-Puttini P, Shoenfeld Y, Doria A (2007) OxLDL/beta2GPI-anti-oxLDL/beta2GPI complex and atherosclerosis in SLE patients. Autoimmun Rev 7:52–58

    Article  CAS  PubMed  Google Scholar 

  36. Schett G, Xu Q, Amberger A, Van der Zee R, Recheis H, Willeit J et al (1995) Autoantibodies against heat shock protein 60 mediate endothelial cytotoxicity. J Clin Invest 96:2569–2577

    Article  CAS  PubMed  Google Scholar 

  37. Lamb DJ, Tickner ML, Dreux AC, El-Sankary W, Hourani SM, Eales-Reynolds LJ et al (2004) Impairment of vascular function following BCG immunisation is associated with immune responses to HSP-60 in the cholesterol-fed rabbit. Atherosclerosis 172:13–20

    Article  CAS  PubMed  Google Scholar 

  38. Harats D, Yacov N, Gilburd B, Shoenfeld Y, George J (2002) Oral tolerance with heat shock protein 65 attenuates Mycobacterium tuberculosis-induced and high-fat-diet-driven atherosclerotic lesions. J Am Coll Cardiol 40:1333–1338

    Article  CAS  PubMed  Google Scholar 

  39. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874

    Article  CAS  PubMed  Google Scholar 

  40. Bixel MG, Petri B, Khandoga AG, Khandoga A, Wolburg-Buchholz K, Wolburg H et al (2007) A CD99-related antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo. Blood 109:5327–5336

    Article  CAS  PubMed  Google Scholar 

  41. van Wanrooij EJ, de Vos P, Bixel MG, Vestweber D, van Berkel TJ, Kuiper J (2008) Vaccination against CD99 inhibits atherogenesis in low-density lipoprotein receptor-deficient mice. Cardiovasc Res 78:590–596

    Article  PubMed  Google Scholar 

  42. Inoue M, Itoh H, Ueda M, Naruko T, Kojima A, Komatsu R et al (1998) Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis. Circulation 98:2108–2116

    CAS  PubMed  Google Scholar 

  43. Petrovan RJ, Kaplan CD, Reisfeld RA, Curtiss LK (2007) DNA vaccination against VEGF receptor 2 reduces atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 27:1095–1100

    Article  CAS  PubMed  Google Scholar 

  44. Hauer AD, van Puijvelde GH, Peterse N, de Vos P, van Weel V, van Wanrooij EJ et al (2007) Vaccination against VEGFR2 attenuates initiation and progression of atherosclerosis. Arterioscler Thromb Vasc Biol 27:2050–2057

    Article  CAS  PubMed  Google Scholar 

  45. Hauer AD, Uyttenhove C, de Vos P, Stroobant V, Renauld JC, van Berkel TJ et al (2005) Blockade of interleukin-12 function by protein vaccination attenuates atherosclerosis. Circulation 112:1054–1062

    Article  CAS  PubMed  Google Scholar 

  46. Madjid M, Naghavi M, Litovsky S, Casscells SW (2003) Influenza and cardiovascular disease: a new opportunity for prevention and the need for further studies. Circulation 108:2730–2736

    Article  PubMed  Google Scholar 

  47. Naghavi M, Barlas Z, Siadaty S, Naguib S, Madjid M, Casscells W (2000) Association of influenza vaccination and reduced risk of recurrent myocardial infarction. Circulation 102:3039–3045

    CAS  PubMed  Google Scholar 

  48. Siscovick DS, Raghunathan TE, Lin D, Weinmann S, Arbogast P, Lemaitre RN et al (2000) Influenza vaccination and the risk of primary cardiac arrest. Am J Epidemiol 152:674–677

    Article  CAS  PubMed  Google Scholar 

  49. Gurevich VS (2005) Influenza, autoimmunity and atherogenesis. Autoimmun Rev 4:101–105

    Article  PubMed  Google Scholar 

  50. Zhu J, Quyyumi AA, Norman JE, Costello R, Csako G, Epstein SE (2000) The possible role of hepatitis A virus in the pathogenesis of atherosclerosis. J Infect Dis 182:1583–1587

    Article  CAS  PubMed  Google Scholar 

  51. Burnett MS, Zhu J, Miller JM, Epstein SE (2003) Effects of hepatitis A vaccination on atherogenesis in a murine model. J Viral Hepatitis 10:433–436

    Article  CAS  Google Scholar 

  52. Scannapieco FA, Bush RB, Paju S (2003) Associations between periodontal disease and risk for atherosclerosis, cardiovascular disease, and stroke. A systematic review. Ann Periodontol 8:38–53

    Article  PubMed  Google Scholar 

  53. Koizumi Y, Kurita-Ochiai T, Oguchi S, Yamamoto M (2008) Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P. gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice. Infect Immun 76:2958–2965

    Article  CAS  PubMed  Google Scholar 

  54. Zahn R, Schneider S, Frilling B, Seidl K, Tebbe U, Weber M, Gottwik M, Altmann E, Seidel F, Rox J, Höffler U, Neuhaus KL, Senges J, Working Group of Leading Hospital Cardiologists (2003) Antibiotic therapy after acute myocardial infarction: a prospective randomized study. Circulation 107:1253–1259

    Article  PubMed  Google Scholar 

  55. Joensen JB, Juul S, Henneberg E, Thomsen G, Ostergaard L, Lindholt JS (2008) Can long-term antibiotic treatment prevent progression of peripheral arterial occlusive disease? A large, randomized, double-blinded, placebo-controlled trial. Atherosclerosis 196:937–942

    Article  CAS  PubMed  Google Scholar 

  56. Sawayama Y, Tatsukawa M, Kikuchi K, Maeda S, Ohnishi H, Furusyo N, Hayashi J (2007) Effect on carotid atherosclerosis of probucol plus levofloxacin for Chlamydia pneumoniae infection. J Infect Chemother 13:92–98

    Article  CAS  PubMed  Google Scholar 

  57. Sherer Y, Shoenfeld Y (2005) Immunomodulation for treatment and prevention of atherosclerosis. Autoimmun Rev 1:21–27

    Article  Google Scholar 

  58. Nilson J, Hansson GK, Shah PK (2005) Immunomodulation of atherosclerosis: implications for vaccine development. Arterioscler Thromb Vasc Biol 25:18–28

    Article  Google Scholar 

Download references

Conflict of interest

YS papering in courts in cases of vaccination and autoimmunity issues.

Author information

Authors and Affiliations

  1. Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo e Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    Jozélio Freire de Carvalho & Rosa Maria R. Pereira

  2. Department of Internal Medicine B, Center for Autoimmune Diseases, Sackler Faculty of Medicine, Sheba Medical Center affiliated to Tel-Aviv University, Tel-Hashomer, 52621, Israel

    Yehuda Shoenfeld

  3. Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel-Aviv University, Tel-Aviv, Israel

    Yehuda Shoenfeld

Authors
  1. Jozélio Freire de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rosa Maria R. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yehuda Shoenfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yehuda Shoenfeld.

Additional information

Carvalho JF received a grant from Federico Foundation.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Carvalho, J.F., Pereira, R.M.R. & Shoenfeld, Y. Vaccination for Atherosclerosis. Clinic Rev Allerg Immunol 38, 135–140 (2010). https://doi.org/10.1007/s12016-009-8145-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-009-8145-y

Keywords

Search

Navigation