RM2e-ΔPly protein immunization induces protection against influenza viruses and its co-infection with Streptococcus pneumoniae in mice

Abstract

Current seasonal influenza A virus (IAV) vaccines only protect against specific virus and require annual reconstitution to accommodate the viral mutations. A universal influenza vaccination that protects against all IAV strains is urgently needed. The influenza matrix protein 2 ectodomain (M2e) is a potential universal IAV vaccine candidate, but it has a low immunogenicity. ΔA146Ply was proved to be an effective protein adjuvant. Therefore, ΔA146Ply was used as an adjuvant of M2e in this study to evaluate its protective effect against IAV-related infection. Herein, a novel rM2e protein containing multiple M2e originated from different species of IAV was constructed and expressed in Escherichia coli (E. coli). Meanwhile, we also constructed and expressed the rM2e-ΔPly protein in E. coli. These proteins were administered intramuscularly to BALB/c mice. rM2e-ΔPly protein induces higher levels of humoral and cellular responses compared with their comprising protein mixture or rM2e alone. rM2e-ΔPly protein enhances the survival rate, reduces viral loads and inflammatory response in lung challenged with PR8. The serum induced by rM2e-ΔPly protein can protect against PR8 by passive immunity and cross-react with multiple M2e peptides derived from different IAV subtypes. After IAV and Streptococcus pneumoniae (S. pneumoniae) co-infection, rM2e-Ply protein can improve survival, lower viral and bacterial burdens, and diminish inflammatory response in the lungs. These results demonstrate that rM2e-ΔPly protein can significantly protect against influenza virus, IAV and S. pneumoniae co-infection, indicating that rM2e-ΔPly protein has the potential to become a universal influenza vaccine.