Development of immune response against H9N2 avian influenza after vaccination

Abstract

Xue, P. (2023). Development of immune response against H9N2 avian influenza after vaccination. PhD thesis, Wageningen University, the Netherlands.The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spilled over from animals to humans is a catastrophe killing more than six million people so far according to World Health Organization (WHO). Like SARS-CoV-2, the respiratory virus, H9N2 avian influenza virus (AIV), can also spill over from animals to humans, and is endemic in poultry flocks in several regions of the world. Some researchers are concerned that H9N2 AIV may be a spark to the emergence of the next influenza pandemic, either directly crossing the species barrier or through the donation of internal genes to a pandemic virus. Like dealing with SARS-CoV-2, vaccination is the main and most effective strategy to control H9N2 AIV. However, most vaccination programs against H9N2 AIV have shown to be ineffective in poultry in practice. Therefore, my project was 1) to figure out what factors may interfere with the H9N2 vaccine efficacy to sufficiently reduce transmission in poultry, 2) to come up with some ideas to improve the vaccine efficacy, and 3) to explore the mechanisms that influence the vaccine efficacy. In chapter 2, I went to several poultry farms for more than three months to collect surveillance data for H9N2 vaccination failure. The data suggests that maternal-derived antibodies (MDAs) may be one of reasons for H9N2 vaccination failure in poultry, which was further corroborated by animal experiments in broilers and specific pathogen-free (SPF) chickens in laboratory in the same chapter 2. In chapter 3, I developed a CpG ODN-based adjuvant that could help the H9N2 inactivated whole virus (IWV) vaccine overcome MDAs, triggering potent humoral immune responses and cytokinesis mRNA expression. In chapter 4, in order to stop transmission of H9N2 AIV, I used turkey herpesvirus (HVT) to express H9 HA protein. The recombinant virus (rHVT-H9) successively induced strong humoral and cellular immune responses, reducing virus shedding and transmission even in the presence of MDAs. In chapter 5, I explored some mechanisms of MDAs interference and found that only complete MDAs interfered with immune responses to vaccination instead of the antigen-binding portion (F(ab) 2 ) or the Fc-binding portion (Fc). In addition, type I chicken interferons (ch-IFNs) helped the H9N2 IWV vaccine overcome MDAs interference inducing potent humoral immune responses. Finally, in chapter 6, I discussed avian immune response after vaccination, the mechanisms of MDAs interference, new measurements of vaccine efficacy against transmission of H9N2 AIV and strategies to improve vaccine efficacy to stop transmission of H9N2 AIV in poultry. Overall, this thesis provides a deeper understanding of H9N2 vaccination failure in poultry and may spark some ideas to stop transmission of respiratory viruses. 20 subtype H9N2 does not prevent virus transmission in chickens. J Virus Erad, 7, 100055. Dadras, H., S. Nazifi & M....