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Mucosal Administration of Lactobacillus casei Surface-Displayed HA1 Induces Protective Immune Responses against Avian Influenza A Virus in Mice

  • Dung T. Huynh (College of Veterinary Medicine, Chungnam National University) ;
  • W.A. Gayan Chathuranga (College of Veterinary Medicine, Chungnam National University) ;
  • Kiramage Chathuranga (College of Veterinary Medicine, Chungnam National University) ;
  • Jong-Soo Lee (College of Veterinary Medicine, Chungnam National University) ;
  • Chul-Joong Kim (College of Veterinary Medicine, Chungnam National University)
  • Received : 2023.07.28
  • Accepted : 2023.10.18
  • Published : 2024.03.28

Abstract

Avian influenza is a serious threat to both public health and the poultry industry worldwide. This respiratory virus can be combated by eliciting robust immune responses at the site of infection through mucosal immunization. Recombinant probiotics, specifically lactic acid bacteria, are safe and effective carriers for mucosal vaccines. In this study, we engineered recombinant fusion protein by fusing the hemagglutinin 1 (HA1) subunit of the A/Aquatic bird/Korea/W81/2005 (H5N2) with the Bacillus subtilis poly γ-glutamic acid synthetase A (pgsA) at the surface of Lactobacillus casei (pgsA-HA1/L. casei). Using subcellular fractionation and flow cytometry we confirmed the surface localization of this fusion protein. Mucosal administration of pgsA-HA1/L. casei in mice resulted in significant levels of HA1-specific serum IgG, mucosal IgA and neutralizing antibodies against the H5N2 virus. Additionally, pgsA-HA1/L. casei-induced systemic and local cell-mediated immune responses specific to HA1, as evidenced by an increased number of IFN-γ and IL-4 secreting cells in the spleens and higher levels of IL-4 in the local lymphocyte supernatants. Finally, mice inoculated with pgsA-HA1/L. casei were protected against a 10LD50 dose of the homologous mouse-adapted H5N2 virus. These results suggest that mucosal immunization with L. casei displaying HA1 on its surface could be a potential strategy for developing a mucosal vaccine against other H5 subtype viruses.

Keywords

Acknowledgement

This work was supported by Chungnam National University The authors thank Dr. Y.K. Choi (Chungbuk National University, South Korea) for providing H5N2/HA sequence-bearing plasmid and mouse-adapted A/Aquatic bird/Korea/W81/2005(H5N2) virus.

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