ORF2 VRPs protected against MNV1.CW3 in both distal ileum (p = 0.005) and MLN (p = 0.02) compared to control VRPs expressing hemagglutinin (HA) from a mouse adapted influenza A virus [41] (HA VRP control group). Controls for VRP vaccination also included PBS. HA VRP controls were not significantly different from PBS controls across all experiments and statistical comparisons for VRP vaccination are therefore shown to HA VRP controls. ORF1 VRPs alone in the distal ileum, or in both the distal ileum and MLN when combined with ORF3 VRPs, had a small but statistically significant effect on MNV1.CW3 levels ( Figure 1B and 1C). ORF3 VRPs alone did not confer significant protection ( Figure 1B and 1C). Together these data show that vaccination with either live virus or ORF2 VRPs can confer shortterm protection against MNV challenge.