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

Current vaccines for influenza are primarily killed whole virus vaccines that elicit antibody responses to the homologous virus but lack protection against heterologous viruses. Using chickens as a model we have explored the possibility of using a live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 virus as a vaccine to generate protective immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Pensylvania/1370/1983 H5N2 virus challenge. Virus replicated in chickens infected with LPAI H1N1 but did not cause clinical disease. In addition, these chickens developed neutralizing antibodies to LPAI H1N1 virus, but not HPAI H5N2, 21 days post infection (DPI). Furthermore, peripheral blood mononuclear cells from H1N1-infected chickens at 20 DPI had antigen specific proliferation and IFN-γ secretion following antigen stimulation to H5N2 indicating a heterologous HPAI H5N2 specific cell mediated immunity (CMI) following LPAI H1N1 infection. Following challenge with HPAI H5N2 virus, all control chickens developed clinical disease, while chickens previously infected with H1N1 did not develop clinical disease and shed significantly less virus by oral and cloacal routes. These results indicated that previous infection with LPAI virus can generate heterologous CMI capable of protecting against HPAI H5N2.