Highly pathogenic avian influenza virus H5N1 from Egypt escapes vaccine-induced immunity but confers clinical protection against a heterologous clade 2.2.1 Egyptian isolate

► Egyptian HPAIV H5N1 lineage 2.2.1var escape immunity induced by heterologous H5N2 vaccines. ► Clinical protection was achieved only against classic Egyptian strains (H5N1 2.2.1pro). ► In spite of clinical protection considerable shedding of 2.2.1pro virus was observed. ► A homologous Egyptian clade 2.2.1var vaccine induced sterile immunity. ► Silent virus spread and consecutive vaccine-driven evolution of HPAIV H5N1 pose evident risks.