Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Preclinical evaluation of efficacy and safety of a new vaccine against Coxsackievirus B1 – Implications for type 1 diabetes development (#93)

Pär Larsson 1 , Lakshmikanth Tadepally 1 , Renata Utorova 1 , Stella Jacobson 1 , Minni Koivunen 2 , Olli H Laitinen 2 , Nicolas Devard 3 , Valerie Lecouturier 3 , Mikael Knip 4 5 , Heikki Hyöty 6 , Malin Flodström-Tullberg 1
  1. Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
  2. Vactech Oy, Tampere, Finland
  3. Sanofi Pasteur, Lyon, France
  4. Children's Hospital, University of Helsinki, Helsinki, Finland
  5. Department of Pediatrics, Tampere University Hospital, Tampere, Finland
  6. Deparment of Virology, University of Tampere, Tampere, Finland

Enterovirus infections (e.g. Coxsackie B viruses, CVBs) have been implicated as environmental triggers of type 1 diabetes (T1D). Recent epidemiological studies suggest that CVB1 infections are associated with the appearance of beta-cell autoantibodies1, an event that almost always precedes clinical disease . A vaccine could determine whether there is a causal relationship between CVB1 infections and the triggering of beta-cell autoimmunity. The development of a vaccine against a virus suspected to induce an autoimmune disease is however a challenging task as the vaccine itself could potentially trigger autoimmunity.

The aim of this study was to evaluate function and safety of a non-adjuvanted, formalin-inactivated prototype CVB1 vaccine in BALB/c and NOD mice. We demonstrate that vaccinated BALB/c and NOD mice produce high titers of neutralizing antibodies to CVB1 without showing vaccine-related adverse side effects. Vaccine efficacy was tested in BALB/c mice and these studies showed that vaccinated animals challenged with CVB1 had no or dramatically reduced levels of virus in target organs. Whether the vaccine triggers or accelerates beta-cell autoimmunity was addressed in pre-diabetic NOD mice. These mice showed no increase in the production of insulin autoantibodies or accelerated onset of diabetes following vaccination. In contrast, challenge with live CVB1 accelerated disease development in a subgroup of pre-diabetic animals.

We conclude that the prototype CVB1 vaccine is safe and confers protection from infection without accelerating beta-cell autoimmunity or diabetes development in NOD mice. Collectively, our studies also suggest that the accelerated disease onset in NOD mice infected with CVBs cannot be related to sequence or structural similarities between self-antigens and structural viral proteins (i.e. molecular mimicry). The efficacy and safety results of our vaccine studies encourage further development of a broad-spectrum enterovirus vaccine that could be used to determine whether enterovirus infections trigger T1D in man.

  1. Laitinen OH, Honkanen H, Pakkanen O, et al. (2013) Coxsackievirus B1 is associated with induction of beta-cell autoimmunity that portends type 1 diabetes. Diabetes, published online before print August 23, 2013, doi: 10.2337/db13-0619.