PMID- 32131431
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2076-393X (Print)
IS  - 2076-393X (Electronic)
IS  - 2076-393X (Linking)
VI  - 8
IP  - 1
DP  - 2020 Mar 2
TI  - Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents 
      Development of Type 2 Diabetes Mellitus.
LID - 10.3390/vaccines8010116 [doi]
LID - 116
AB  - 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 beta-cell 
      secretory products-extracellular aggregates are cytotoxic for insulin-producing 
      beta-cells and are associated with beta-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 1beta (IL-1beta). We 
      offer the first cost-effective and safe disease-modifying approach targeting 
      islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing 
      physiological IAPP function.
FAU - Roesti, Elisa S
AU  - Roesti ES
AUID- ORCID: 0000-0002-3599-4960
AD  - Department of Rheumatology, Immunology and Allergology (RIA), University 
      Hospital, University of Bern, 3010 Bern, Switzerland.
AD  - Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, 
      Switzerland.
FAU - Boyle, Christina N
AU  - Boyle CN
AD  - Institute of Veterinary Physiology, University of Zurich, 8006 Zurich, 
      Switzerland.
FAU - Zeman, Daniel T
AU  - Zeman DT
AUID- ORCID: 0000-0003-3348-4657
AD  - Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 
      4031 Basel, Switzerland.
FAU - Sande-Melon, Marcos
AU  - Sande-Melon M
AD  - Institute of Anatomy, University of Bern, 3010 Bern, Switzerland.
AD  - Spanish National Centre for Cardiovascular Research (CNIC), 28029 Madrid, Spain.
FAU - Storni, Federico
AU  - Storni F
AD  - Department of Rheumatology, Immunology and Allergology (RIA), University 
      Hospital, University of Bern, 3010 Bern, Switzerland.
AD  - Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, 
      Switzerland.
AD  - Department of Visceral Surgery and Medicine, University Hospital of Bern, 3010 
      Bern, Switzerland.
FAU - Cabral-Miranda, Gustavo
AU  - Cabral-Miranda G
AD  - Department of Rheumatology, Immunology and Allergology (RIA), University 
      Hospital, University of Bern, 3010 Bern, Switzerland.
FAU - Knuth, Alexander
AU  - Knuth A
AD  - National Center for Cancer Care & Research (NCCCR), 3050 Doha, State of Qatar.
FAU - Lutz, Thomas A
AU  - Lutz TA
AUID- ORCID: 0000-0002-5056-8548
AD  - Institute of Veterinary Physiology, University of Zurich, 8006 Zurich, 
      Switzerland.
FAU - Vogel, Monique
AU  - Vogel M
AD  - Department of Rheumatology, Immunology and Allergology (RIA), University 
      Hospital, University of Bern, 3010 Bern, Switzerland.
AD  - Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, 
      Switzerland.
FAU - Bachmann, Martin F
AU  - Bachmann MF
AD  - Department of Rheumatology, Immunology and Allergology (RIA), University 
      Hospital, University of Bern, 3010 Bern, Switzerland.
AD  - Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, 
      Switzerland.
AD  - Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology 
      (CCMP), The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
LA  - eng
GR  - 310030_185114/SNSF/
PT  - Journal Article
DEP - 20200302
PL  - Switzerland
TA  - Vaccines (Basel)
JT  - Vaccines
JID - 101629355
PMC - PMC7157615
OTO - NOTNLM
OT  - T2DM
OT  - amyloid
OT  - islet amyloid polypeptide
OT  - vaccine
OT  - virus-like particle
COIS- The authors declare no conflict of interest.
EDAT- 2020/03/07 06:00
MHDA- 2020/03/07 06:01
PMCR- 2020/03/02
CRDT- 2020/03/06 06:00
PHST- 2020/02/11 00:00 [received]
PHST- 2020/02/25 00:00 [revised]
PHST- 2020/02/26 00:00 [accepted]
PHST- 2020/03/06 06:00 [entrez]
PHST- 2020/03/07 06:00 [pubmed]
PHST- 2020/03/07 06:01 [medline]
PHST- 2020/03/02 00:00 [pmc-release]
AID - vaccines8010116 [pii]
AID - vaccines-08-00116 [pii]
AID - 10.3390/vaccines8010116 [doi]
PST - epublish
SO  - Vaccines (Basel). 2020 Mar 2;8(1):116. doi: 10.3390/vaccines8010116.