Prior infection of pigs with a recent human H 3 N 2 influenza virus confers minimal cross‐protection against a E uropean swine H 3 N 2 virus

Background H3 N 2 influenza viruses circulating in humans and E uropean pigs originate from the pandemic A / H ong K ong/68 virus. Because of slower antigenic drift in swine, the antigenic divergence between swine and human viruses has been increasing. It remains unknown to what extent this results in a reduced cross‐protection between recent human and swine H 3 N 2 influenza viruses. Objectives We examined whether prior infection of pigs with an old [ A / V ictoria/3/75 ( A / V ic/75)] or a more recent [ A / W isconsin/67/05 ( A / W is/05)] human H 3 N 2 virus protected against a E uropean swine H 3 N 2 virus [sw/ G ent/172/08 (sw/ G ent/08)]. Genetic and antigenic relationships between sw/ G ent/08 and a selection of human H 3 N 2 viruses were also assessed. Results After challenge with sw/ G ent/08, all challenge controls had high virus titers in the entire respiratory tract at 3 days post‐challenge and nasal virus excretion for 5–6 days. Prior infection with sw/ G ent/08 or A / V ic/75 offered complete virological protection against challenge. Pigs previously inoculated with A / W is/05 showed similar virus titers in the respiratory tract as challenge controls, but the mean duration of nasal shedding was 1·3 days shorter. Unlike sw/ G ent/08‐ and A / V ic/75‐inoculated pigs, A / W is/05‐inoculated pigs lacked cross‐reactive neutralizing antibodies against sw/ G ent/08 before challenge, but they showed a more rapid antibody response to sw/ G ent/08 than challenge controls after challenge. Cross‐protection and serological responses correlated with genetic and antigenic differences. Conclusions Infection immunity to a recent human H 3 N 2 virus confers minimal cross‐protection against a E uropean swine H 3 N 2 virus. We discuss our findings with regard to the recent zoonotic infections of humans in the United States with a swine‐origin H 3 N 2 variant virus.