Toll-like receptor ligands enhance vaccine efficacy against a virulent Newcastle disease virus challenge in chickens

Authors: Lee, Chang; Bakre, Abhijeet; Olivier, Timothy; Alvarez-Narvaez, Sonsiray; HARRELL, TELVIN - Oak Ridge Institute For Science And Education (ORISE); Conrad, Steven

Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2023
Publication Date: 10/11/2023
Citation: Lee, C.W., Bakre, A.A., Olivier, T.L., Alvarez Narvaez, S., Harrell, T.L., Conrad, S.J. 2023. Toll-like receptor ligands enhance vaccine efficacy against a virulent Newcastle disease virus challenge in chickens. Pathogens. 12(10):1230. https://doi.org/10.3390/pathogens12101230.
DOI: https://doi.org/10.3390/pathogens12101230

Interpretive Summary: Newcastle disease (ND) is one of the most important poultry diseases worldwide. In spite of routine immunization with live and killed vaccines incorporated into vaccination programs, ND remain a considerable cause of economic loss to the poultry industry. Therefore, alternative or complementary strategies that can enhance the vaccine efficacy and boost protective host immune responses are needed. To enhance the efficacy of the current Newcastle disease vaccine, we have selected two potential adjuvants (ODN-1826 and Imiquimod) that can enhance innate immunity and antiviral response. We demonstrated that vaccine groups adjuvanted with Imiquimod or ODN-1826 induced higher and more uniform antibody titer among birds compared with live vaccine alone group. In addition, adjuvanted vaccines demonstrated greater protective efficacy in terms of reduction in virus shedding titer and number of birds shedding the challenge virus. These results demonstrate the potential use of immunostimulatory adjuvants as mucosal vaccine enhancers and warrant further optimization for efficacy and practical application in chickens.

Technical Abstract: To enhance the efficacy of the current Newcastle disease vaccine, we have selected potential adjuvants that target well-characterized pattern recognition receptors: the toll-like receptors (TLRs). Imiquimod is a small-molecule activator of TLR7, which is a sensor of dsDNA. ODN-1826 is a mimetic of CpG DNA and ligates TLR21 (a chicken homologue of TLR9 in mammals). The activation of TLRs leads to antiviral responses, including the induction of type I interferons (IFNs). In this study, birds were vaccinated intranasally with a live LaSota strain with or without imiquimod or ODN-1826 (50 g/bird). Two weeks after vaccination, the birds were challenged with a virulent Newcastle disease virus (chicken/CA/212676/2002). Both adjuvants (imiquimod or ODN-1826) induced higher and more uniform antibody titers among vaccinated birds compared with the live vaccine-alone group. In addition, adjuvanted vaccines demonstrated greater protective efficacy in terms of the reduction in virus-shedding titer and the number of birds shedding the challenge virus at 2 and 4 days post-challenge. A differential expression of antiviral and immune-related genes was observed among groups from tissues (Harderian gland, trachea, cecal tonsil, and spleen) collected 1 and 3 days after treatment. These results demonstrate the potential of TLR-targeted adjuvants as mucosal vaccine enhancers and warrant a further characterization of immune correlates and optimization for efficacy.