“…Because substitutions in the HA1 subunit play a much more important role than those in the HA2 subunit in vaccine escape, the results support the idea that mass vaccination, as an evolutionary selective force, facilitates the emergence of vaccine-resistant viruses. This is also consistent with previous reports that many amino acid substitutions in the HA1 subunit of H5N1 HPAI viruses occurred at antigenic sites [3,25,40]. In addition, it has also been found by others that the substitution rate of viruses may be elevated by selection of immune escape [41,42].…”