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Atherosclerosis antigens as targets for immunotherapy

Nature Cardiovascular Research volume 2, pages 1129–1147 (2023)Cite this article

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Abstract

Atherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction and stroke, underlying the first cause of mortality worldwide. Adaptive immunity plays critical roles in atherosclerosis, and numerous studies have ascribed both atheroprotective and atherogenic functions to specific subsets of T and B cells. However, less is known on how antigen specificity determines the protective or adverse outcome of such adaptive responses. Understanding antigen triggers in atherosclerosis is crucial to delve deeper into mechanisms of disease initiation and progression and to implement specific immunotherapeutic approaches, including vaccination strategies. Here we review the role of adaptive immunity in atherosclerosis and the insights that single-cell technology has provided into the function of distinct immune cell subsets. We outline the most relevant atherosclerosis antigens and antibodies reported to date and examine their immunotherapeutic potential. Finally, we review the most promising vaccination-based clinical trials targeting the adaptive immune system.

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Fig. 1: BCR and TCR characterization of human and mouse samples using single-cell techniques.
Fig. 2: Overview of atherosclerosis-associated antigens and antibodies.
Fig. 3: Experimental vaccination strategies targeting the immune system.

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Acknowledgements

I.R.-G. is a fellow of the Ministerio de Educación y Formación Profesional (FPU20/01814) A.R.-R. is fellow of the research training program funded by Ministerio de Ciencia, Innovación y Universidades (PRE2020-091873) and A.R.R. is supported by Spanish National Center for Cardiovascular Research (CNIC). A.R.R. has received funding from la Caixa Banking Foundation under the project code HR22-0253 and from PID2019-106773RB-I00/AEI/10.13039/501100011033 (Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 Programa Estatal de I + D + i Orientada a los Retos de la Sociedad Retos Investigación: Proyectos I + D + i 2016, Ministerio de Economía, Industria y Competitividad) and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) as well as from INMUNOVAR-CM P2022/BMD-733 grant funded by the Biomedicine Program 2022 of Comunidad Autónoma de Madrid. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation), and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). Correspondence should be addressed to A.R.R.

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  1. B Lymphocyte Lab, Novel Mechanisms of Atherosclerosis Program, Spanish National Center for Cardiovascular Research, Madrid, Spain

    Irene Raposo-Gutiérrez, Ana Rodríguez-Ronchel & Almudena R. Ramiro

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Raposo-Gutiérrez, I., Rodríguez-Ronchel, A. & Ramiro, A.R. Atherosclerosis antigens as targets for immunotherapy. Nat Cardiovasc Res 2, 1129–1147 (2023). https://doi.org/10.1038/s44161-023-00376-x

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