Mice used in vaccination studies were immunized with 3610 7 PFU of MNV1.CW1 [28] , MNV1.CW3 [31] , or control Type I Lang reovirus per orally (p.o.) in 25 ml of DMEM containing 10% fetal bovine serum (Hyclone, Logan, UT) (cDMEM). VRP immunizations were with 2.5610 6 infectious units (IU) of each VRP expressing MNV1.CW3 ORF1, ORF2, or ORF3 individually or in groups of 2-3 VRPs; Chiba virus ORF2 or Lordsdale virus ORF2 in 10 ml or 50 ml volume by footpad inoculation (into the subcutaneous space) [65] on day 0 and boosted on day 21. HA VRP and PBS immunizations in 10 ml or 50 ml volume by footpad inoculation [65] on day 0 and boosted on day 21 served as controls for all VRP immunizations. Mice were challenged with 3610 7 PFU of MNV1.CW3 at specified times after boost and tissues harvested three days post-challenge. Controls for VRP vaccination included PBS or VRPs expressing hemagglutinin (HA) from a mouse adapted influenza A virus [41] . PBS served as a control for HA VRP in these experiments in the event that HA VRP had a significant effect on MNV replication. HA VRP controls were not significantly different from PBS controls in all experiments and both are presented in all figures for completeness.