Abstract B89: Determining the underlying protective mechanisms of bivalent Marek’s disease vaccine to prevent tumor induction

Abstract

Abstract Marek’s disease (MD) is a lymphoproliferative disease in chicken and the most frequently diagnosed cancer in the animal kingdom. The causative pathogen is the ubiquitous Marek’s disease virus (MDV), a highly oncogenic alphaherpesvirus. Since the 1970s, poultry flocks have been controlled by widespread vaccination (e.g., 1 million birds per hour in the US alone); MD vaccines were revolutionary because they were the first to prevent tumors. Unfortunately, MD vaccines do not prevent viral infection or spread, which has likely promoted the repeated evolution of MDV field strains to higher virulence. Hence, in order to develop more effective MD vaccines, especially those that might prevent horizontal transmission, it is important to gain knowledge on the underlying mechanisms on tumor prevention and viral replication. In addition, chickens serve as a natural model of the disease to study viral oncology and cancer vaccines. The current study focuses on understanding how the commonly used MD vaccines SB-1 and HVT work better in combination (88% protection) compared to either SB-1 or HVT vaccine alone (44% and 24% protection, respectively). We find that bivalent SB-1+HVT vaccine is able to suppress MDV replication in peripheral blood mononuclear cells (PBMCs) until the end of the trial (8 weeks) while either monovalent vaccine failed to control MDV viremia beyond 2 weeks post-challenge. SB-1+HVT also shows the highest efficacy to inhibit tumor formation compared to either monovalent vaccine. To gain insight of how SB-1+HVT can inhibit tumors, we determined the replication of SB-1 and HVT vaccine and find that replication of SB-1 and HVT is different with respect to time after vaccination and tissue tropism. Specifically, SB-1 replicates increasingly in spleen from 1 day post challenge (DPC) to 14 DPC, contrasting to the replication of HVT, which is found only in bursa at 1 DPC. The differences in replication pattern of SB-1 and HVT vaccine may promote different sets of immune cells corresponding to immune protection. Additionally, SB-1+HVT shows the highest immune activation observed by the highest percent CD8 T-cell response. Further experiments are under way to determine whether the induced CD8 response results in antiviral effect at the early stage of infection or antitumor activity as well as identifying associated cytokines induced in the protection provided by SB-1+HVT vaccination. Citation Format: Supawadee Umthong, Hans Cheng, John Dunn. Determining the underlying protective mechanisms of bivalent Marek’s disease vaccine to prevent tumor induction [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B89.