Of note, vaccination with VP1 via the subcutaneous route provided significant protection despite the fact that the vaccination occurred systemically, while protection was read out at a mucosal site. This indicates that an active systemic immune response can provide protection against norovirus infection, and a mucosal vaccine may not be necessary to vaccinate against norovirus infection. Importantly, systemic vaccination was dependent on T cells, indicating that the relevant cells can traffic to the intestine after peripheral VRP-based vaccination.