Recombinant hemagglutinin displaying on yeast reshapes congenital lymphocyte subsets to prompt optimized systemic immune protection against avian influenza infection

Han Zhang; Zexing Li; Huixia Zhang; Yanyu Guo; Xinyi Zhang; Lilin Zhang; Liu Yang; Shujun Li; Changyan Li; Daqing Cui; Ruyu Xie; Yongqing Li; Jinhai Huang

doi:10.3389/fmicb.2023.1153922

Recombinant hemagglutinin displaying on yeast reshapes congenital lymphocyte subsets to prompt optimized systemic immune protection against avian influenza infection

Front Microbiol. 2023 May 31:14:1153922. doi: 10.3389/fmicb.2023.1153922. eCollection 2023.

Authors

Han Zhang^#¹, Zexing Li^#¹, Huixia Zhang¹, Yanyu Guo¹, Xinyi Zhang¹, Lilin Zhang¹, Liu Yang¹, Shujun Li¹, Changyan Li¹, Daqing Cui¹, Ruyu Xie¹, Yongqing Li², Jinhai Huang¹

Affiliations

¹ School of Life Sciences, Tianjin University, Tianjin, China.
² Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agricultural and Forestry Sciences, Beijing, China.

^# Contributed equally.

Abstract

Introduction: Prophylactic vaccination is regarded as the most effective means to control avian flu infection. Currently, there is a need for a universal vaccine that provides broad and long-lasting protection against influenza virus. Meanwhile, although yeast-based vaccines have been used in clinic, studies are still required to further understand the molecular mechanism of yeast-based vaccines under physiological conditions.

Methods: We generated a yeast-based vaccine against influenza hemagglutinin (HA) of H5, H7 and H9 using surface displaying technology and evaluated the protective efficacy of chickens after exposure to H9N2 influenza virus.

Results: Oral yeast vaccine provided less clinical syndrome, reduced viral loading and alleviated airway damage significantly. Compared to the commercial inactivated vaccine, yeast vaccine stimulated the activation of splenic NK and APCs cells and boosted TLR7-IRF7-IFN signaling in spleen. Meanwhile, γδ T cells in the bursa of Fabricius were activated and the innate lymphoid cells (ILCs) in the bursa of Fabricius promoted the CILPs to differentiate to ILC3 cells in oral yeast birds. Moreover, the reshaped gut microbiota and a suppressed Th17-IL17-mediated inflammation in intestine was observed in oral yeast chickens, which might facilitate the recovery of intestinal mucosal immunity upon virus infection. Collectively, our findings suggest that oral yeast based multivalent bird flu vaccines provide an attractive strategy to update host defense function via reshapes of multi-systemic immune homeostasis.

Keywords: Saccharomyces cerevisiae; avian influenza virus; chicken; innate immunity; vaccine.

Grants and funding

This work was supported by the Tianjin Synthetic Biotechnology Innovation Capability Improvement Project in China (TSBICIP-KJGG-014) and the Key Underprop Project of Tianjin Municipal Science and Technology Bureau (20YFZCSN00340).