Pathogenicity and escape to pre-existing immunity of a new genotype of swine influenza H1N2 virus that emerged in France in 2020.

In 2020, a new genotype of swine H1N2 influenza virus (H1N2-HA 1C.2.4) was identified in France. It rapidly spread within the pig population and supplanted the previously predominant H1N1-HA 1C.2.1 virus. To characterize this new genotype which is genetically and antigenically distant from the other H1Nx viruses detected in France, an experimental study was conducted to compare the outcomes of H1N2 and H1N1 infections in pigs and evaluate the protection conferred by the only inactivated vaccine currently licensed in Europe containing an HA 1C (clade 1C.2.2) antigen. Infection with H1N2 induced stronger clinical signs and earlier shedding than H1N1. The neutralizing antibodies produced following H1N2 infection were unable to neutralize H1N1, and vice versa, whereas the cellular-mediated immunity cross-reacted. Vaccination slightly altered the impact of H1N2 infection at the clinical level, but did not prevent shedding of infectious virus particles. It induced a cellular-mediated immune response towards H1N2, but did not produce neutralizing antibodies against this virus. As in vaccinated animals, animals previously infected by H1N1 developed a cross-reacting cellular immune response but no neutralizing antibodies against H1N2. However, H1N1 pre-infection induced a better protection against the H1N2 infection than vaccination, probably due to higher levels of non-neutralizing antibodies and a mucosal immunity. Altogether, these results showed that the new H1N2 genotype induced a severe respiratory infection and that the actual vaccine was less effective against this H1N2-HA 1C.2.4 than against H1N1-HA 1C.2.1, which may have contributed to the H1N2 epizootic and dissemination in pig farms in France.