A multivalent vaccine covering all Coxsackievirus B (CVB) serotypes protects against acute CVB infection and CVB-induced diabetes in mice.

Background

Coxsackievirus B (CVB) viruses are associated with Type 1 diabetes (T1D), however, whether they are causal remains unknown. A strategy to determine their involvement in T1D could involve vaccination of at-risk individuals with a vaccine targeting the six known CVB serotypes (CVB1-6) and successive monitoring of disease incidence. Currently, no commercially available CVB vaccines exist, thereby rendering this option unobtainable. Previously, we demonstrated that a CVB1 vaccine is immunogenic and protects against acute CVB1 infections and CVB1-induced diabetes in mice. Cross-protection against other CVB serotypes does not occur, necessitating the need for a hexavalent CVB1-6 vaccine. Here, we preclinically test a hexavalent CVB vaccine in murine models.

Methods

CVB1-6 serotypes were inactivated in formalin to produce the hexavalent non-adjuvanted CVB vaccine. NOD and SOCS-1-tg NOD mice (a CVB-induced diabetes model), were vaccinated 3 times and then challenged with CVBs. Weight and blood glucose (used to monitor diabetes onset) were measured regularly. Neutralising antibodies in sera were measured by standard neutralization assay. Viraemia and viral dissemination after CVB infection were assessed by standard plaque assay and histological analysis.

Results

The CVB1-6 vaccine had no detrimental effects on weight or blood glucose. Neutralizing antibodies against all six CVB serotypes were induced with equivalent neutralising capacities after three vaccinations. The CVB1-6 vaccine protected against acute CVB infection and prevented CVB-induced diabetes in the SOCS-1-tg mouse model for virus-induced diabetes. As far as we are aware, this is the first time a vaccine targeting the six CVB serotypes has been produced and shown to be effective in preventing infection. This preclinical proof-of-concept study provides the basis for the further development of a hexavalent CVB vaccine for use in humans to determine whether CVBs are involved in T1D, and if they were found to be casual, could provide a preventative treatment for T1D.