B6 mice were infected intranasally (i.n.) with 10 plaque forming units (PFU) of PR/8 IAV and challenged 21 days later with 10,000 PFU of HK/X31 IAV i.n. 7 days after HK/X31 infection, spleen, lung, and serum were collected for intracellular cytokine staining (ICS) and PR/8 nucleoprotein (NP)-specific IgG ELISA. PR/8 and HK/X31 IAVs have different hemagglutinin (HA) and neuraminidase (NA) surface proteins and are not recognized by any cross-reactive neutralizing antibodies. These IAV strains share 6 internal genes derived from PR/8 – NP, the polymerase complex heterotrimer (PB2, PB1 and PA), matrix protein (M) and nonstructural protein (NS).