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Open AccessArticle

Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus

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Department of Rheumatology, Immunology and Allergology (RIA), University Hospital, University of Bern, 3010 Bern, Switzerland
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Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, Switzerland
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Institute of Veterinary Physiology, University of Zürich, 8006 Zürich, Switzerland
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Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland
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Institute of Anatomy, University of Bern, 3010 Bern, Switzerland
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Spanish National Centre for Cardiovascular Research (CNIC), 28029 Madrid, Spain
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Department of Visceral Surgery and Medicine, University Hospital of Bern, 3010 Bern, Switzerland
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National Center for Cancer Care & Research (NCCCR), 3050 Doha, State of Qatar
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Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology (CCMP), The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
*
Author to whom correspondence should be addressed.
Elisa Roesti, PhD, Immunology, RIA, Inselspital, University of Bern, Sahlihaus 1/2, 3010 Bern, Switzerland.
Vaccines 2020, 8(1), 116; https://doi.org/10.3390/vaccines8010116
Received: 11 February 2020 / Revised: 25 February 2020 / Accepted: 26 February 2020 / Published: 2 March 2020
Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These—originally β-cell secretory products—extracellular aggregates are cytotoxic for insulin-producing β-cells and are associated with β-cell loss and inflammation in T2DM advanced stages. Due to the absence of T2DM preventive medicaments and the presence of only symptomatic drugs acting towards increasing hormone secretion and action, we aimed at establishing a novel disease-modifying therapy targeting the cytotoxic IAPP deposits in order to prevent the development of T2DM. We generated a vaccine based on virus-like particles (VLPs), devoid of genomic material, coupled to IAPP peptides inducing specific antibodies against aggregated, but not monomeric IAPP. Using a mouse model of islet amyloidosis, we demonstrate in vivo that our vaccine induced a potent antibody response against aggregated, but not soluble IAPP, strikingly preventing IAPP depositions, delaying onset of hyperglycemia and the induction of the associated pro-inflammatory cytokine Interleukin 1β (IL-1β). We offer the first cost-effective and safe disease-modifying approach targeting islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing physiological IAPP function. View Full-Text
Keywords: islet amyloid polypeptide; amyloid; T2DM; virus-like particle; vaccine islet amyloid polypeptide; amyloid; T2DM; virus-like particle; vaccine
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MDPI and ACS Style

Roesti, E.S.; Boyle, C.N.; Zeman, D.T.; Sande-Melon, M.; Storni, F.; Cabral-Miranda, G.; Knuth, A.; Lutz, T.A.; Vogel, M.; Bachmann, M.F. Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus. Vaccines 2020, 8, 116.

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