Haemagglutinin displayed on the surface of Lactococcus lactis confers broad cross-clade protection against different H5N
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(2020) 19:193 Lei et al. Microb Cell Fact https://doi.org/10.1186/s12934-020-01453-7
Open Access
RESEARCH
Haemagglutinin displayed on the surface of Lactococcus lactis confers broad cross‑clade protection against different H5N1 viruses in chickens Han Lei1* , Tong Gao1, Qianhong Cen1 and Xiaojue Peng2
Abstract Background: The 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. Results: Recombinant 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. Conclusion: This 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. Keywords: L. lactis/pNZ8148-spax-HA, Cross protection, H5N1 cross-clade vaccine Background 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]. Numerous H5N1 influenza vaccines from *Correspondence: [email protected] 1 College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China Full list of author information is available at the end of the article
candidate clade 1 and 2 viruses have been approved for production [3]. In addition, most licensed inactivated and live-attenuated H5N1 vaccines are produced in embryonated chicken eggs infected with the seed viruses, and the manufacturing process can take up 9 months [4, 5]. Unfortunately, the highly diverse genetic nature and the rapid evolution of H5N1 viruses has resulted in titre reduction in high-quality allantoic fluid [6]. Furthermore, the currently licensed H5N1 influenza vaccines and inactivated egg-derived whole-virus H5N1 vaccines provide inadequate immunogenicity against infection with H5N1 belonging to a different clade [7], and the current vaccine manufacturing capacity would be inadequate during an emerging H5N1 pandemi
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