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Immunomodulation of atherosclerosis with a vaccine

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 639–646 (2005)Cite this article

Abstract

Experimental observations have established that the innate and adaptive immune mechanisms both have roles in the modulation of atherosclerosis. The complex function that the immune system has in the pathophysiology of atherosclerosis is highlighted by the fact that both proatherogenic and atheroprotective effects of immune activation can be demonstrated. An immune response to the protein and lipid components of oxidized LDL cholesterol has been observed in experimental models, and immunization with these antigens has generally reduced atherosclerosis. The findings suggest the tantalizing possibility that an atheroprotective vaccine can be developed. Our laboratories have identified several antigenic epitopes in the human apolipoprotein B100 component of LDL cholesterol. Active immunization with some of these epitopes has reduced atherosclerosis in hyperlipidemic mice. We believe, therefore, that a vaccine based on apolipoprotein B100-related peptide could have a role in reducing atherosclerosis. In this review, we discuss the possible immunologic mechanisms by which vaccines against atherosclerosis might work and the ways in which such treatment might be most effectively administered.

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Figure 1: A schematic representation of the potential juxtaposed roles of the innate immune response in atherosclerosis.
Figure 2: A schematic representation of the potential juxtaposed roles of the adaptive immune response to specific antigens.

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Acknowledgements

We gratefully acknowledge the contributions of many colleagues in the Atherosclerosis Research Center at Cedars Sinai Medical Center and at the University of Lund to this work. We thank the Eisner Foundation, the Heart Fund, United Hostesses, and the Entertainment Industry Foundation for support. We used hybridoma technology provided by Dr Patricia Gearhart at the NIH in our work on this topic.

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Authors and Affiliations

  1. Director, Division of Cardiology and Atherosclerosis Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Prediman K Shah

  2. Cardiologist in the Division of Cardiology and Atherosclerosis Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Kuang-Yuh Chyu

  3. an Assistant Professor Division of Cardiology and Atherosclerosis Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Gunilla N Fredrikson

  4. Professor of Medicine in the Department of Clinical Sciences, Malmö University Hospital, Sweden

    Jan Nilsson

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  1. Prediman K Shah
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Correspondence to Prediman K Shah.

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Competing interests

PK Shah and J Nilsson are co-inventors and hold patents for peptide vaccines for atherosclerosis. By institutional patent the rights are assigned to Cedars-Sinai Medical Center, Los Angeles, CA, USA, and Lund University, Sweden, respectively.

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Shah, P., Chyu, KY., Fredrikson, G. et al. Immunomodulation of atherosclerosis with a vaccine. Nat Rev Cardiol 2, 639–646 (2005). https://doi.org/10.1038/ncpcardio0372

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