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

Rösti, Elisa S.; Boyle, Christina N; Zeman, Daniel T; Sande Melon, Marcos; Storni, Federico; Cabral-Miranda, Gustavo; Knuth, Alexander; Lutz, Thomas A; Vogel, Monique; Bachmann, Martin (2020). Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus. Vaccines, 8(1) MDPI 10.3390/vaccines8010116

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Rösti, Elisa Simona; Sande Melon, Marcos; Storni, Federico Lorenzo; Cabral de Miranda, Gustavo; Vogel, Monique and Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2076-393X

Publisher:

MDPI

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

20 Oct 2020 16:33

Last Modified:

07 Jan 2021 10:10

Publisher DOI:

10.3390/vaccines8010116

PubMed ID:

32131431

Uncontrolled Keywords:

T2DM amyloid islet amyloid polypeptide vaccine virus-like particle

BORIS DOI:

10.7892/boris.146997

URI:

https://boris.unibe.ch/id/eprint/146997

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