Avian influenza A H9N2 viruses are widespread among domestic poultry and we
re recently isolated from humans with respiratory illness in China. Two ant
igenically and genetically distinct groups of H9N2 viruses (G1 and G9) are
prevalent in China. To evaluate a strategy for vaccination, we compared G1
and G9 viruses for their relative immunogenicity and cross-protective effic
acy. Infection of BALB/c mice with representative viruses of either group p
rotected against subsequent challenge with the homologous or heterologous H
9N2 virus in the absence of detectable cross-reactive serum hemagglutinatio
n inhibition antibody. Mice injected intramuscularly with inactivated G1 wh
ole virus vaccine were completely protected from challenge with either H9N2
virus. In contrast, mice administered inactivated G9 vaccine were only par
tially protected against heterologous challenge with the G1 virus. These re
sults have implications for the development of human vaccines against H9N2
viruses, a priority for pandemic preparedness.