Monovalent H5 vaccine based on epitope-chimeric HA provides broad cross-clade protection against variant H5N1 viruses in mice

- A broadly immunogenic H5 was developed by epitope engineering with representative epitopes from different major H5N1 clades.
- Epitope-chimeric H5N1 elicited high titers of HI and VN antibodies against different H5N1s (clade 1, 2, 4 and 7) in mice.
- Monovalent vaccine with epitope-chimeric H5N1 protected mice from lethal challenge with H5N1s of clade 1.0, 2.1, 2.2 and 2.3.

H5N1 HPAI virus continues to be a severe threat for public health, as well as for the poultry industry, due to its high mortality and antigenic drift rate. There is no monovalent vaccine available which provides broad protection against those major circulating strains. In the present study, a monovalent H5 vaccine strain was developed with antigenic sequence analysis and epitope mutations. H5 from Indonesia strain (A/Indonesia/CDC669/2006) was used as backbone sequence. Three amino acids were mutated to express immunogenic epitopes from other circulating H5N1s in the backbone. RG influenza virus expressing the epitope-chimeric H5 can react in HI with multiple H5 monoclonal antibodies which fail to neutralize wild type CDC669. High titers in HI and virus neutralization against different clades H5N1s (clade 1, 2, 4 and 7) were detected using sera from mice immunized with the epitope-chimeric H5N1. The monovalent vaccine with RG-epitope-chimeric H5N1 protected mice from lethal challenge with H5N1s of different clades, including clade 1.0, 2.1, 2.2 and 2.3. This study indicates that the broad immune response elicited by this single H5N1 virus allows it to be a promising candidate for a monovalent H5 universal vaccine.