Lack of cross-protection between European H1N1 and H1N2 swine influenza viruses

Background: Swine influenza viruses (SIVs) of H1N2 subtype have recently become established in several European countries, and they cocirculate with H1N1 and H3N2 viruses. The H1N2 virus haemagglutinin (HA) appears to be of human origin and fails to cross-react with avian-like H1N1 SIVs in vitro. This study examines whether in vivo cross-protection occurs between H1N1 and H1N2 viruses isolated in Belgium. Methods: Influenza virus-seronegative pigs were inoculated first with Sw/Gent/7625/99 (H1N2) or Sw/Belgium/1/98 (H1N1), or left uninoculated. Four weeks later, all pigs were challenged with the H1N2 virus. We examined H1N2 antibody titres prior to challenge, and clinical signs and virus replication after challenge. Results: H1N2 antibodies were found exclusively in the pigs previously infected with H1N2, and these were protected against disease and infection. Fever and respiratory signs typical of H1N2 infection developed in the challenge control pigs and the H1N1-immune pigs. In both groups, all pigs had H1N2 virus in the lungs at 24 h and in nasal swabs during the first week after challenge. In H1N1-immune pigs, however, the mean virus titre in the lungs was 1.9 log10 EID50/g lower than in the challenge controls. Similarly, the total amount of virus excreted was significantly reduced and virus excretion was on the average 1.4 days shorter. Conclusions: Pigs immune after H1N1 subtype infection are not protected against H1N2 infection and disease. This is in agreement with the antigenic difference in the HAs of these viruses. Our data, however, suggest partial heterosubtypic immunity between H1N1 and H1N2, which may be mediated by the cytotoxic T lymphocyte response. D 2001 Elsevier Science B.V. All rights reserved.