In the present study, samples were collected from wild and domestic waterfowls to detect recently circulating HPAI H5Nx viruses. Partial HA gene sequencing followed by phylogenetic analysis of the obtained sequences of five selected isolates was performed. Phylogenetic analysis revealed clustering of the three H5N8 isolates in clade 2.3.4.4b, with other Egyptian H5N8 isolates with amino acid identity percent with each other ranging from (96.9% - 99.3%). The two H5N1 isolates clustered in clade 2.2.1.2 with other recent Egyptian isolates. The amino acid identity percent between vaccinal strains was ranging from (88.2% - 89.6%) with H5N8 field isolates and (96.5% - 99%) with H5N1 field isolates. The amino acid identity percent between H5N8 and H5N1 field isolates ranging from (86.3% - 87.8%). The antigenic relatedness between the two HPAI local isolates (H5N1 and H5N8) was low (R value 24.8%) indicating major antigenic difference between the two subtypes. Also, a major subtype difference in antigenicity (R value 20.7-31.0%) was also detected between the local HPAI H5N8 isolate and the three vaccinal strains. While, a minor subtype difference (R value 38.7-68.7%) was detected among the examined H5N1 local isolate and the three vaccinal strains. Our results support that, HPAI H5N8 virus is genetically and antigenically distinct from HPAI H5N1 virus. Also, some commercial vaccines which are used to control avian influenza in Egypt are genetically and antigenically distinct from HPAI H5N8 virus currently circulating in Egypt.