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 (H1_avN2-HA 1C.2.4) was identified in France. It rapidly spread within the pig population and supplanted the previously predominant H1_avN1-HA 1C.2.1 virus. To characterize this new genotype which is genetically and antigenically distant from the other H1_avNx viruses detected in France, an experimental study was conducted to compare the outcomes of H1_avN2 and H1_avN1 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 H1_avN2 induced stronger clinical signs and earlier shedding than H1_avN1. The neutralizing antibodies produced following H1_avN2 infection were unable to neutralize H1_avN1, and vice versa, whereas the cellular-mediated immunity cross-reacted. Vaccination slightly altered the impact of H1_avN2 infection at the clinical level, but did not prevent shedding of infectious virus particles. It induced a cellular-mediated immune response towards H1_avN2, but did not produce neutralizing antibodies against this virus. As in vaccinated animals, animals previously infected by H1_avN1 developed a cross-reacting cellular immune response but no neutralizing antibodies against H1_avN2. However, H1_avN1 pre-infection induced a better protection against the H1_avN2 infection than vaccination, probably due to higher levels of non-neutralizing antibodies and a mucosal immunity. Altogether, these results showed that the new H1_avN2 genotype induced a severe respiratory infection and that the actual vaccine was less effective against this H1_avN2-HA 1C.2.4 than against H1_avN1-HA 1C.2.1, which may have contributed to the H1_avN2 epizootic and dissemination in pig farms in France.