dc.contributor.author | Roesti, Elisa S | |
dc.contributor.author | Boyle, Christina N | |
dc.contributor.author | Zeman, Daniel T | |
dc.contributor.author | Sande-Melon, Marcos | |
dc.contributor.author | Storni, Federico | |
dc.contributor.author | Cabral-Miranda, Gustavo | |
dc.contributor.author | Knuth, Alexander | |
dc.contributor.author | Lutz, Thomas A | |
dc.contributor.author | Vogel, Monique | |
dc.contributor.author | Bachmann, Martin F | |
dc.date.accessioned | 2020-03-25T07:25:28Z | |
dc.date.available | 2020-03-25T07:25:28Z | |
dc.date.issued | 2020-03 | |
dc.identifier.citation | Vaccines (Basel). 2020; 8(1):116 | es_ES |
dc.identifier.issn | 2076-393X | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9321 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | These studies were funded by a project grant from the Swiss National Foundation (SNF). We acknowledge the technical assistance of Sydney W. Pence and Faith Slubowski at the Institute of Veterinary Physiology, University of Zürich. We appreciate the kind possibility given by Nanolive (Lausanne, Switzerland) for the opportunity and the collaborative acquisition of tomographic pictures. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | T2DM | es_ES |
dc.subject | Amyloid | es_ES |
dc.subject | Islet amyloid polypeptide | es_ES |
dc.subject | Vaccine | es_ES |
dc.subject | Virus-like particle | es_ES |
dc.title | Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 32131431 | es_ES |
dc.format.volume | 8 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 116 | es_ES |
dc.identifier.doi | 10.3390/vaccines8010116 | es_ES |
dc.contributor.funder | Swiss National Foundation | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/vaccines8010116 | es_ES |
dc.identifier.journal | Vaccines | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Desarrollo del Epicardio y su Papel en la Regeneración | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |