This invention provides a modified
hemagglutinin (HA)
protein for preparing a broad-spectrum vaccine against H9 avian influenza, a broad-spectrum vaccine based on the HA
protein, a preparation method, and applications. The modified HA
protein is obtained through the following strategy:
consensus sequences are constructed as immunogenic backbones for the HA sequences of H9 avian influenza viruses at different epidemic periods; based on this, two types of functional mutations are directionally introduced: one type involves
transplanting key
epitope residues targeted by known broad-spectrum antibodies, and the other type involves
neutralizing epitope residues predicted based on viral evolutionary patterns. The modified HA protein of this invention can maintain a highly similar overall fold and
trimer interface to the
wild type, can be efficiently expressed in eukaryotic systems, and can induce high levels of neutralizing antibodies with broad-spectrum cross-protective effects in target animals. It provides a core
antigen candidate for the development of a new generation of H9 broad-spectrum vaccines and has broad application prospects.