MDA-LDL vaccination induces athero-protective germinal center-derived antibody responses

Martos-Folgado, I.; Lorenzo, C.; Busse, C. E.; Mur, S. M.; Cobos, L.; Martin-Ventura, J. L.; Escola-Gil, J. C.; Wardemann, H.; Ramiro, A. R.

doi:10.1101/2021.10.25.465690

bioRxiv · 10.1101/2021.10.25.465690

MDA-LDL vaccination induces athero-protective germinal center-derived antibody responses

Martos-Folgado, I.·Lorenzo, C.·Busse, C. E.·Mur, S. M.·Cobos, L.·Martin-Ventura, J. L.·Escola-Gil, J. C.·Wardemann, H.·Ramiro, A. R.

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Abstract

Atherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction and stroke and is the leading cause of mortality worldwide. Immunization of pro-atherogenic mice with malondialdehyde-modified low-density lipoprotein (MDA-LDL) neo-antigen is athero-protective. However, the immune response to MDA-LDL and the mechanisms responsible for this athero-protection are not completely understood. Here, we find that immunization of mice with MDA-LDL elicits memory B cells, plasma cells, and switched anti-MDA-LDL antibodies as well as clonal expansion and affinity maturation, indicating that MDA-LDL triggers a bona fide germinal center antibody response. Further, Prdm1fl/fl Aicda-Cre+/ki Ldlr-/- pro-atherogenic chimeras, which lack germinal center-derived plasma cells, show accelerated atherosclerosis. Finally, we show that MDA-LDL immunization is not athero-protective in mice lacking germinal-center derived plasma cells. Our findings give further support to the development of MDA-LDL-based vaccines for the prevention or treatment of atherosclerosis.

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Martos-Folgado, I., Lorenzo, C., Busse, C. E., Mur, S. M., Cobos, L., Martin-Ventura, J. L., Escola-Gil, J. C., Wardemann, H., Ramiro, A. R.. 2021-10-26. MDA-LDL vaccination induces athero-protective germinal center-derived antibody responses. https://doi.org/10.1101/2021.10.25.465690

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