Exposure to A/California/04/09 induces heterosubtypic cross-reactivity and protective immunity against H3N2 influenza viruses. We infected cohorts of BALB/c/mice sublethally with live mouse-adapted swine-origin A/CA/04/2009, collected their sera 1 mo postinfection, and tested their ability to cross-react with a panel of H3N2 viruses, using HAI assay (A). We then challenged these animals with 3 × LD50 mouse-adapted H3N2 viruses, A/Aichi/2/68 or A/Victoria/3/75, and monitored them for survival (B) and signs of morbidity (C), as reflected in the body weight changes up to 14 d postchallenge. The graphs represent the mean ± SD of five mice per group.