Location: Endemic Poultry Viral Diseases Research
Project Number: 6040-32000-083-000-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2021
End Date: Sep 30, 2026
Objective:
1. Predict and characterize the evolution of virulent strains of Gallid alphaherpesvirus type 2 Marek's Disease Virus (MDV) in chicken production systems.
1.A. Detect and predict the evolution of MDV strains.
1.B. Conduct studies to identify and characterize mechanisms associated with the evolution of MDV.
1.C. Identify viral genes with mutations that are associated with MDV virulence and verify the effects on virus pathogenesis.
2. Elucidate mechanisms of immunity that can enhance Marek’s Disease vaccinal control.
2.A. Characterize virus-host interactions in innate immune pathways that contribute to MD susceptibility or immunity, to inform the development of highly effective vaccines against very virulent strains.
2.B. Define mechanisms of cellular immune evasion that contribute to MD pathogenicity, and which can be targeted through recombinant vaccines to improve vaccine efficacy.
3. Develop safe and highly effective MDV platforms that convey protection against very virulent strains.
3.A. Development and evaluation of novel recombinant MD vaccines.
3.B. Utilization of novel adjuvants for enhanced immunogenicity of live-attenuated vaccines against MD.
4. Develop a novel Infectious laryngotracheitis virus (ILTV) vaccine platform that is safe, efficacious, and cost-effective.
4.A. Development of an infectious clone of ILTV.
4.B. Develop improved vaccines against ILTV.
Approach:
We plan to investigate the role of innate immunity in Marek's Disease Virus (MDV) infection, identify host and viral determinants involved in transmission that undoubtedly plays a role in virus evolution, and define cellular immune evasion mechanisms that contribute to MD-induced pathogenicity. These effects will lead to (1) novel, more efficacious vaccines that include recombinants expressing cancer driver genes and a Newcastle disease virus vector expressing antigens of MDV and Infectious laryngotracheitis virus (ILTV) to create a trivalent vaccine, and (2) fundamental information that can be applied for more effective and sustainable MD control. Live attenuated ILT vaccines are also imperfect, and not only can they revert to virulence but are highly recombinogenic, making them capable of generating new virulent strains. An infectious clone of ILTV will be chemically synthesized and used to create novel vaccines with enhanced replicative fidelity, reduced capacity for reversion, and the inability to establish latent infections. Lipid nanoparticles encapsulating mRNAs expressing the prefusion conformation of the essential fusion proteins, glycoprotein B orthologues of ILTV and MDV, will also be developed.
