Human IVIG treatment in a neurological disease model for Enterovirus A71 infection in 28-day-old AG129 mice

Enterovirus A71 can cause serious neurological disease in young children. Animal models for EV-A71 are needed to evaluate potential antiviral therapies. Existing models have limitations, including lack of lethality or crucial disease signs. Here we report the development of an EV-A71 model in 28-day-old mice. Virus was serially passaged until it produced consistent lethality and rear-limb paralysis. Onset of disease occurred between days 6–9 post-infection, with mortality following weight loss and neurological signs on days 9–14. In addition, a single administration of human intravenous immunoglobulin at doses of 200, 400 and 800 mg/kg at 4h post-infection was evaluated in the model. Protection from weight loss, neurological signs, and mortality (between 50 and 89%) were observed at doses of 400 mg/kg or greater. Based on these results, IVIG was selected for use as a positive control in this acute model, and suggest that IVIG is a potential therapeutic for EV-A71 infections. •This report describes a new model for EV-A71 infection in 28-day-old mice for evaluation of antiviral therapeutics.•This report also describes the process of mouse-adaptation of EV-A71.•The mouse-adapted virus shows consistent lethality and relevant disease signs, including rear-limb paralysis in mice.•Seventeen antiviral compounds shown to have in vitro activity against EV-A71 were evaluated in this model.•Only human intravenous immunoglobulin showed protection, and was selected for use as a positive control in this model.