Prior infection of chickens with H1N1 avian influenza virus elicits heterologous protection against highly pathogenic H5N2

► Virus replicated in chickens infected with LPAI H1N1 but did not cause clinical disease. ► Chickens developed cross reactive cellular immunity to H5N2. ► Chickens previously infected with H1N1 did not develop clinical disease following H5N2 challenge. ► Protection was observed in the absence of H5 specific antibodies.