Despite numerous observations supporting a possible role for enteroviruses in some cases of type 1 diabetes (T1D), proof that enterovirus infections are involved in T1D is lacking. A way to test their involvement in T1D would be to develop a vaccine. This is nonetheless a challenging task due to the existence of over 100 different members in the enterovirus genus. The use of a vaccine against a virus suspected to induce an autoimmune disease could also be associated with a risk if the vaccine itself induces an autoimmune reaction via for example molecular mimicry. Another important bottleneck is that vaccine effectiveness is low in neonates and young infants, while enterovirus infections are common already before the age of 3 months. Here the preclinical testing of the efficacy and safety of a new prototype vaccine against a selected enterovirus will be discussed. Using well-established and relevant experimental model systems we have tested the vaccine’s potential to block virus infection. We have also investigated whether such a vaccine has undesired effects by triggering or accelerating autoimmunity. Finally, we have studied whether maternally transferred antibodies can provide protection from infection and T1D development in young offspring.