Novel Immunoprophylaxis Strategies for Antigen and Nanobody Delivery to Combat Avian Influenza

The purpose of this co-operative agreement is to develop a two-pronged immunoprophylactic strategy for the prevention and control of highly pathogenic avian influenza (HPAI) in poultry. We aim to develop a rapid and cost-effective immunotherapeutic designed to protect highly susceptible young chicks and to be deployed during emergency outbreaks. In parallel, we will also develop a vectored vaccine capable of inducing durable immune responses. By combining a rapid-acting immunotherapeutic with a robust vectored vaccine, this project aims to establish a comprehensive strategy for the prevention, control, and emergency preparedness of HPAI. Objective 1 will focus on developing an avian adeno-associated virus (AAAV) vector, termed AVI-Bloc, that encodes broadly neutralizing anti-influenza virus antibody in different formats (IgY, IgA and scFv). These constructs will be evaluated for efficacy in chickens using both individual and mass administration, including oral, aerosol and gel-spray delivery. We will generate a packaging cell line for low-cost production of AVI-Bloc vectors. Objective 2 will focus on establishing a DIVA-compatible vaccine platform using Rispens strain of Marek’s disease virus to deliver H5N1 hemagglutinin (HA) and neuraminidase (NA) antigens. We will develop immune-complexed, and M-cell targeting MDV vectored vaccines and evaluate their immunogenicity in birds. In objective 3, the protective efficacy of AVI-Bloc immunotherapy will be rigorously tested in challenge studies, particularly its ability to protect highly susceptible young chicks and provide rapid protection during emergency outbreaks. The protective efficacy of MDV Rispens-based immune-complexed and M-cell targeting vaccine candidates will be evaluated in HPAI challenge studies. We will measure neutralizing antibody responses, durability of protection, and the effects of immune-complexed antigen and M-cell targeting on the immunogenicity and protective efficacy of vaccine candidates. Key deliverables include the AAAV-based immunotherapeutic, low-cost scalable packaging cell line, a bivalent vaccine for HPAI and Marek’s disease, innovative tools for immune-complexed and M-cell targeting vaccine design along with the protocols for developing these immunoprophylaxis tools. The primary beneficiaries will be small and large-scale poultry producers, animal health biologics manufacturers, research scientists, poultry veterinarians, and policymakers. The outcomes are expected to provide rapidly deployable and effective immunoprophylactic tools for strengthening HPAI outbreak preparedness.

Funder: USDA APHIS

Amount: $1,999,861

PI: Lok Joshi, College of Veterinary Medicine