Enhanced humoural and cellular immune responses to influenza H7N9 antigen HA1–2 fused with flagellin in chickens

BMC Veterinary Research

Research Article

Zhiming Pan¹  Xilong Kang¹  Dan Xiong¹  Maozhi Hu¹  Xinan Jiao¹  Li Song¹ 

[1] Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 225009, Yangzhou, Jiangsu, China;Jiangsu Key Laboratory of Zoonosis, Yangzhou University, 48 East Wenhui Road, 225009, Yangzhou, Jiangsu, China;Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China;Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu, China;

关键词: Avian influenza A (H7N9) virus;    Haemagglutinin globular head;    Flagellin;    Subunit vaccine;    Chicken;   

DOI  :  10.1186/s12917-017-1106-4

 received in 2017-03-14, accepted in 2017-06-09,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSudden increases in the number of human A (H7N9) cases reported during December and January have been observed in previous years. Most reported infection cases are due to prior exposure to live poultry or potentially contaminated environments. Low pathogenicity of influenza A (H7N9) virus in avian species complicates timely discovery of infected birds. Therefore, there is a pressing need to develop safe and effective anti-H7N9 vaccines for poultry to reduce the risk of human infection and prevent the emergence of novel mutated strains. In addition to a good antigen, an effective vaccine also requires an appropriate adjuvant to enhance its immunogenicity. Previously, we generated an H7N9 influenza recombinant subunit vaccine (HA1–2-fliC), in which haemagglutinin globular head domain (HA1–2) was fused with flagellin (fliC), a potent TLR5 ligand, and demonstrated that HA1–2-fliC elicited effective HA1–2-specific immune responses in mice.ResultsIn this study, we determined flagellin-induced expression profiles of cytokines and chemokines in different types of avian immune cells in vitro and ex vivo. We found that flagellin significantly increased the expression levels of CXCL inflammatory chemokines (CXCLi1 and CXCLi2) and CCL chemokines (MIP-1β and MCP-3) in avian macrophage HD11 cells. In addition, HA1–2-fliC induced significant upregulation of cytokines (IL-1β, IL-6, IL-18 and IFN-γ) and chemokines (CXCLi1, CXCLi2 and MIP-1β) in ex vivo splenic lymphocytes and peripheral blood mononuclear cells (PBMCs), suggesting that flagellin promoted immune responses of avian cells in vitro. We also evaluated specific humoural and cellular immune responses induced by HA1–2-fliC and found that chickens immunised intramuscularly with HA1–2-fliC showed significantly higher HA1–2-specific immunoglobulin (Ig)G titers in serum. Furthermore, HA1–2-fliC potentiated cellular immune responses, as reflected by an increase in CD4+ and CD8+ T cells and proliferation of PBMCs. Significantly higher levels of IFN-γ and IL-4 in PBMCs from chickens vaccinated with HA1–2-fliC further indicated that HA1–2-fliC promoted a balanced Th1/Th2 immune response.ConclusionsWe demonstrated that the use of the flagellin as an adjuvant potentiated immunogenicity of influenza subunit vaccine HA1–2 in vitro and in vivo. These findings provide a basis for the development of H7N9 influenza HA1–2 subunit vaccines for chickens.

【 授权许可】

CC BY   
© The Author(s). 2017