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

作者：Larsson Par G; Lakshmikanth Tadepally; Laitinen Olli H; Utorova Renata; Jacobson Stella; Oikarinen Maarit; Domsgen Erna; Koivunen Minni R L; Chaux Pascal; Devard Nicolas; Lecouturier Valerie; Almond Jeffrey; Knip Mikael; Hyoty Heikki; Flodstrom Tullberg Malin^*

来源：Diabetologia, 2015, 58(2): 346-354.

DOI：10.1007/s00125-014-3436-0

• Autoimmune
• Cox sackievirus
• Enterovirus
• Neutralising antibodies
• Non-obese diabetic mouse
• Type 1 diabetes
• Vaccine

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.
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.
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.
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.

• 出版日期2015-2