Protection against a European H1N2 swine influenza virus in pigs previously infected with H1N1 and/or H3N2 subtypes

A novel swine influenza virus, H1N2, circulates in European swine populations together with H1N1 and H3N2 viruses. This study examines whether post-infection immunity to H1N1 and/or H3N2 viruses provides cross-protection against H1N2 infection. Pigs (n=51) were inoculated intranasally with either Sw/Belgium/1/98 (H1N1) or Sw/Flanders/1/98 (H3N2), or with both viruses at a 5-week interval. Control groups were left uninoculated or inoculated with Sw/Gent/7625/99 (H1N2). Four weeks later, all the pigs were challenged intranasally and intratracheally with a high H1N2 virus dose. The challenge control pigs showed typical influenza symptoms, and all had high H1N2 virus titres in the lungs and nasal virus excretion during 6 or 7 days. The H1N2-immune pigs showed total clinical and virological protection. Pigs immune against H1N1 or H3N2 only were not protected against disease and virus replication in the lungs, but virus excretion was 2 days shorter. By contrast, pigs immune against both H1N1 and H3N2 did not show disease and H1N2 virus replication was either undetectable or markedly reduced. Haemagglutination inhibition (HI) and virus neutralisation (VN) tests indicated that cross-protection against H1N2 was probably not mediated by antibodies against the haemagglutinin (HA). Antibodies inhibiting the neuraminidase (NA) of H1N2 were at minimal levels in H3N2 only-immune pigs, but they were consistently found in (H1N1+H3N2)-immune pigs. The immune response against the internal proteins, which are relatively conserved in H1N1, H3N2 and H1N2 viruses, may play a significant role in protection against H1N2. Given the severe challenge model used here, cross-protection against H1N2 could be more pronounced under natural conditions of infection.