Haemagglutinin displayed on the surface of Lactococcus lactis confers broad cross-clade protection against different H5N1 viruses in chickens

Han Lei,Xiaojue Peng,Tong Gao,Qianhong Cen

doi:10.1186/s12934-020-01453-7

Han Lei, Xiaojue Peng + Show 2 more

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https://doi.org/10.1186/s12934-020-01453-7

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Abstract

BackgroundThe highly pathogenic avian influenza (HPAI) H5N1 virus poses a potential threat to the poultry industry. The currently available avian influenza H5N1 vaccines for poultry are clade-specific. Therefore, an effective vaccine for preventing and controlling H5N1 viruses belonging to different clades needs to be developed.ResultsRecombinant L. lactis/pNZ8148-Spax-HA was generated, and the influenza virus haemagglutinin (HA) protein of A/Vietnam/1203/2004 (H5N1) was displayed on the surface of Lactococcus lactis (L. lactis). Spax was used as an anchor protein. Chickens vaccinated orally with unadjuvanted L. lactis/pNZ8148-Spax-HA could produce significant humoral and mucosal responses and neutralizing activities against H5N1 viruses belonging to different clades. Importantly, unadjuvanted L. lactis/pNZ8148-Spax-HA conferred cross-clade protection against lethal challenge with different H5N1 viruses in the chicken model.ConclusionThis study provides insights into the cross-clade protection conferred by unadjuvanted L. lactis/pNZ8148-Spax-HA, and the results might help the establishment of a promising platform for the development of a safe and effective H5N1 cross-clade vaccine for poultry.

Highlights

The highly pathogenic avian influenza (HPAI) H5N1 virus poses a potential threat to the poultry industry
Characterization of HA protein expressed on the surface of L. lactis L. lactis/pNZ8148-Spax-HA was generated by fusing the HA gene of A/Vietnam/1203/2004 lacking a signal peptide and a transmembrane domain with Spax via a GS linker (Fig. 1a)
L. lactis/ pNZ8148-Spax-HA was incubated with mouse anti-HA monoclonal antibody for direct labelling

Summary

Introduction

The highly pathogenic avian influenza (HPAI) H5N1 virus poses a potential threat to the poultry industry. Due to its high mortality and antigen drift rate, the highly pathogenic avian influenza (HPAI) H5N1 virus is associated with severe disease and poses a serious threat to the poultry industry [1]. HPAI H5N1 viruses have undergone significant genetic diversification, and to date, 10 viral clades, denoted clades 0 to 9, have been identified. Among these clades, clade 2 exhibits significant genetic variation and has been classified into numerous subclades [2]. A monovalent H5 vaccine with RG-epitope-chimeric H5N1 protects mice from lethal challenge with H5N1 viruses of different clades, including clades 1, 2.1, 2.2 and 2.3 [10]. A vesicular stomatitis virus-based influenza vaccine administered via a single immunization confers rapid protection against different H5N1 clades in a mouse model [17]

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