IFN-α armed gE elicits superior immunogenicity compared to unmodified antigens and flagellin armed gE in mice

•IFN-α was first applied in the HZ vaccine, and the results in mice showed that the IFN-α–gE–Fc vaccine was a candidate vaccine for HZ.•IFN-α and flagellin were compared for the first time under the same conditions. IFN-α could produce stronger cellular immunity than flagellin.•The expression system suitable for the IFN-α–gE–Fc fusion protein was designed through expression vector screening and linker peptide screening. Compared with the marketed recombinant herpes zoster vaccine (Shingrix), IFN-α–gE–Fc can replace current used MPL adjuvant. At the same time, the immunogenicity of the IFN-α–gE–Fc + AQ was not weaker than that of the marketed recombinant zoster vaccine. Herpes zoster (HZ) induces significant pain and discomfort, which can seriously affect the quality of life of patients. At present, there is no specific treatment for HZ, and the mosteffective HZ control is vaccination. The main obstacle to developing an effective HZ vaccine is poorly induced cellular immune response. In this study, the IFN-α–gE–Fc fusion protein induced higher levels of humoral and cellular immunity compared to the unengineered gE antigen and higher levels of cellular immunity compared to the flagellin–gE–Fc fusion protein in a murine model. Compared with the marketed recombinant herpes zoster vaccine (Shingrix), IFN-α–gE–Fc can replace current used MPL adjuvant. At the same time, the immunogenicity of the IFN-α–gE–Fc + AQ was not weaker than that of the marketed recombinant zoster vaccine. The novel fusion protein provides a candidate entity for the development of a safe and effective novel HZ vaccine.