A laboratory-generated reassortant H5 hemagglutinin (HA)/H1N1 virus containing four mutations in H5N1 HA become airborne transmissible among mammals. Here we constructed 15 H5N1 pseudoviruses containing single and combinations of these mutations, and showed that these H5N1 pseudoviruses were sensitive to neutralizing antibodies from H5N1-infected patients and conserved H5N1 HA1 sequence-immunized mice. These results indicate that antibodies in patients currently infected by H5N1 and those induced by vaccines containing conserved sequences in HA1 of wild-type H5N1 are highly effective in cross-neutralizing future H5N1 mutants with airborne transmissibility, suggesting that human flu pandemics potentially caused by these H5N1 variants can be preventable.