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Mol Immunol . rM2e-ΔPly protein immunization induces protection against influenza viruses and its co-infection with Streptococcus pneumoniae in mice

tetano

Editor, Senior Moderator
Mol Immunol


. 2022 Oct 25;152:86-96.
doi: 10.1016/j.molimm.2022.10.006. Online ahead of print.
rM2e-ΔPly protein immunization induces protection against influenza viruses and its co-infection with Streptococcus pneumoniae in mice


Ting Guo[SUP] 1 [/SUP], Jiangming Xiao[SUP] 1 [/SUP], Lian Li[SUP] 1 [/SUP], Wenlong Xu[SUP] 1 [/SUP], Yuan Yuan[SUP] 1 [/SUP], Yibing Yin[SUP] 1 [/SUP], Xuemei Zhang[SUP] 2 [/SUP]



Affiliations

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.

Keywords: Co-infection; Influenza a virus; Influenza matrix protein 2 ectodomain; Streptococcus pneumoniae; Universal influenza vaccine.
 
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