title: A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models.
abstract: OBJECTIVE
  Enterovirus infections have been implicated in the aetiology of autoimmune type 1 diabetes. A vaccine could be used to test the causal relationship between enterovirus infections and diabetes development. However, the development of a vaccine against a virus suspected to induce an autoimmune disease is challenging, since the vaccine itself might trigger autoimmunity. Another challenge is to select the enterovirus serotypes to target with a vaccine. Here we aimed to evaluate the function and autoimmune safety of a novel non-adjuvanted prototype vaccine to Coxsackievirus serotype B1 (CVB1), a member of the enterovirus genus.
  
  
  METHODS
  A formalin-inactivated CVB1 vaccine was developed and tested for its immunogenicity and safety in BALB/c and NOD mice. Prediabetic NOD mice were vaccinated, infected with CVB1 or mock-treated to compare the effect on diabetes development.
  
  
  RESULTS
  Vaccinated mice produced high titres of CVB1-neutralising antibodies without signs of vaccine-related side effects. Vaccinated mice challenged with CVB1 had significantly reduced levels of replicating virus in their blood and the pancreas. Prediabetic NOD mice demonstrated an accelerated onset of diabetes upon CVB1 infection whereas no accelerated disease manifestation or increased production of insulin autoantibodies was observed in vaccinated mice.
  
  
  CONCLUSIONS
  We conclude that the prototype vaccine is safe and confers protection from infection without accelerating diabetes development in mice. These results encourage the development of a multivalent enterovirus vaccine for human use, which could be used to determine whether enterovirus infections trigger beta cell autoimmunity and type 1 diabetes in humans.
authors.affiliation: The Center for Infectious Medicine, Department of Medicine HS, Karolinska Institutet, Karolinska University Hospital Huddinge F59, SE-141 86, Stockholm, Sweden.
authors.forename: Pär G
authors.initials: PG
authors.lastname: Larsson
authors.forename: Tadepally
authors.initials: T
authors.lastname: Lakshmikanth
authors.forename: Olli H
authors.initials: OH
authors.lastname: Laitinen
authors.forename: Renata
authors.initials: R
authors.lastname: Utorova
authors.forename: Stella
authors.initials: S
authors.lastname: Jacobson
authors.forename: Maarit
authors.initials: M
authors.lastname: Oikarinen
authors.forename: Erna
authors.initials: E
authors.lastname: Domsgen
authors.forename: Minni R L
authors.initials: MR
authors.lastname: Koivunen
authors.forename: Pascal
authors.initials: P
authors.lastname: Chaux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Devard
authors.forename: Valerie
authors.initials: V
authors.lastname: Lecouturier
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Almond
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.forename: Malin
authors.initials: M
authors.lastname: Flodström-Tullberg
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism*; D003384:Coxsackievirus Infections / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D004769:Enterovirus Infections / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D014765:Viral Vaccines / Q000494:pharmacology*
chemical_list: D000914:Antibodies, Viral; D014765:Viral Vaccines