Date of Completion

1-3-2018

Embargo Period

1-8-2018

Keywords

self-adjuvanted, nanoparticle, coiled-coil, vaccine, chickens, viral respiratory diseases, avian influenza, infectious bronchitis

Major Advisor

Mazhar Khan

Associate Advisor

Antonio Garmendia

Associate Advisor

Peter Burkhard

Associate Advisor

Theodore Girshick

Field of Study

Pathobiology

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Avian influenza (AI) and avian infectious bronchitis (IB) are two highly contagious diseases affecting respiratory systems in avian species, caused by avian influenza virus (AIV) and infectious bronchitis virus (IBV), respectively. AI and IB cause enormous economic losses to the poultry industry. Vaccination is the cornerstone in controlling AI and IB. However, the development of effective vaccines for these two diseases is challenging due to the highly mutable nature of these two RNA viruses. We used our self-assembling protein nanoparticles (SAPNs) to display the conserved influenza (M2e and Helix C) and IBV (the second coiled-coil sequence of S2 protein and receptor binding domain) antigens in their native oligomerization states. To further improve the immunogenicity of the SAPNs, we designed and incorporated the TLR5 agonist flagellin into the SAPNs to generate self-adjuvanted SAPNs. Chickens vaccinated with the self-adjuvanted SAPNs induce significantly higher levels of antibodies than those with unadjuvanted SAPNs and show higher cross-neutralizing activity compared to a commercial inactivated virus vaccine. Vaccinated chickens with the AI SAPN are protected from challenge with a highly pathogenic avian influenza. Our IBV vaccine prototypes have demonstrated the ability to induce high levels of antibodies, significantly potentiate immune memory, and significantly reduced tracheal virus shedding 2 and 4 days post challenge with IBV M41 strain. Lower histopathologic scores were observed in the vaccinated group versusthe nonvaccinated group. These data presented in this work indicate that we have successfully designed and implemented our self-adjuvanted SAPNs for use as vaccine candidates for avian influenza and infectious bronchitis. We have demonstrated self-adjuvanted SAPN vaccine prototypes are protective against challenge bythe two avian respiratory viral pathogens. It is suggested that they could be used as a stand-alone – or possibly even better – as an additional component to an established AI or IB vaccine to broaden the protection of the vaccine. Furthermore, with these findings in mind, we can expand our self-adjuvanted SAPN technology for use in many different diseases that have been traditionally difficult to develop effective vaccine candidates for including malaria, tuberculosis, HIV and many more.

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