Development of effective
vaccines to prevent
influenza, particularly highly pathogenic
avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant
influenza vaccine candidates by fusing
hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human
IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two
recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1
proteins and an inactivated heterologous H5N1 virus. Both
proteins were able to cross-neutralize
infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two
vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the
recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1
influenza vaccine, providing cross-protection against
infections by divergent strains of highly pathogenic H5N1 virus.