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Seroreactivity to H3N2 swine influenza viruses (SIVs) was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg. Sera were analysed by haemagglutination inhibition (HI) and virus neutralisation (VN) assays targeting a European H3N2 SIV, a North American H3N2 variant of swine origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005. HI antibodies (titre?≥?10) against European H3N2 SIV were almost exclusively detected in those born before 1990, of whom 70% were seropositive. HI antibodies against H3N2v were predominantly found in those born before 2000, with 86% seropositive. Titres against the North American H3N2v were higher than against the European H3N2 SIV. VN patterns were similar, but with higher rates and titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to North American H3N2v virus. Finally, we found a strong correlation between HI titres against the European H3N2 SIV and H3N2v and their respective human ancestors, A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies in human serum samples reflect serological cross-reactivity with historical human H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.


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