2026-06-14T05:05:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/93212024-09-27T08:00:38Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Roesti, Elisa S
author
Boyle, Christina N
author
Zeman, Daniel T
author
Sande-Melon, Marcos
author
Storni, Federico
author
Cabral-Miranda, Gustavo
author
Knuth, Alexander
author
Lutz, Thomas A
author
Vogel, Monique
author
Bachmann, Martin F
funder
Swiss National Foundation
2020-03-25T07:25:28Z
2020-03-25T07:25:28Z
2020-03
Vaccines (Basel). 2020; 8(1):116
10.3390/vaccines8010116
2076-393X
Vaccines
32131431
http://hdl.handle.net/20.500.12105/9321
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.
eng
T2DM
Amyloid
Islet amyloid polypeptide
Vaccine
Virus-like particle
Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus
journal article
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URL
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VaccinationAgainstAmyloidogenicAggregates_2020.pdf
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suppl.figure 2 - food intake.tif
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suppl.figure 1 - amylin aa sequence.tif
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https://repisalud.isciii.es/bitstreams/89106d78-fed1-4de7-a162-d1f0eca6fe42/download
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VaccinationAgainstAmyloidogenicAggregates_2020.pdf.txt