Adaptation of seasonal influenza virus H1N1 and H3N2 vaccine strains in BALB/c mouse pneumonitis model

Objective To investigate the possibility of adaptation seasonal influenza virus H1N1 and H3N2 vaccine strains in BALB/C mice. Methods BALB/c mice were infected with wild-type virus and lungs were dissected out at peak of virus multiplication to generate the first passage of mouse adapted virus (P1), which was subjected serial mouse lung-to-lung passages (from P1 to P10). Pathogenicity and genome sequences of wide-type and mouse-adapted virus were compared. Results For H3N2 vaccine strain, virus titer was under detection at any passages. In contrast, for H1N1 vaccine strain, virus replication ability and pathogenicity increased by lung-to-lung passage. Genome sequence analysis of H1N1wt and H1N1MA indicated that mutation of HA-N142D contributed to the enhanced virulence. Conclusions H3N2 vaccine strain was difficult to replicate in mice while H1N1 vaccine strain could effectively replicate in BALB/c mice and mutation of HA-N142D contributed to the enhanced virulence. Key words: Influenza A virus; Influenza vaccine; Mice, inbred BALB C