Towards a mechanistic understanding of the synergistic response induced by bivalent Marek’s disease vaccines to prevent lymphomas

Authors: UMTHONG, SUPAWADEE - Michigan State University; Dunn, John; Cheng, Hans

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/2/2019
Publication Date: 10/8/2019
Citation: Umthong, S., Dunn, J.R., Cheng, H.H. 2019. Towards a mechanistic understanding of the synergistic response induced by bivalent Marek’s disease vaccines to prevent lymphomas. Vaccine. 37(43):6397-6404. https://doi.org/10.1016/j.vaccine.2019.09.003.
DOI: https://doi.org/10.1016/j.vaccine.2019.09.003

Interpretive Summary: Mareks's disease (MD) is an economically important problem of the poultry industry, which is characterized by tumors following infection with Marek's disease virus (MDV). To control MD, widespread vaccination has been employed since the 1970s. Unfortunately, MDV field strains have repeatedly emerged to overcome the current MD vaccines, thus, it is necessary to produce new MD vaccines. In an effort to understand MD vaccinal protection, this effort characterized two MD vaccines alone and in combination, which varied in vaccinal protection. We find vaccinal protection is correlated with where and how long the vaccines replicate in the bird. This knowledge will help guide the rationale production of more effective MD vaccines.

Technical Abstract: Background Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by Marek’s disease virus (MDV), an oncogenic a-herpesvirus. Since 1970, MD has been controlled by widespread vaccination; however, more effective MD vaccines are needed to counter more virulent MDV strains. The bivalent vaccine combination of SB-1 and herpesvirus of turkey (HVT) strain FC126 has been widely used. Nonetheless, the mechanism(s) underlying this synergistic effect has not been investigated. Methods Three experiments were conducted where SB-1 or HVT were administered as monovalent or bivalent vaccines to newly hatched chickens, then challenged five days later with MDV. In Experiment 1, levels of MDV replication in PBMCs were measured over time, and tumor incidence and vaccinal protection determined. In Experiment 2, MDV and vaccine strains replication levels in lymphoid organs were measured at 1, 5, 10, and 14'days post-challenge (DPC). In Experiment 3, to verify that the bursa was necessary for HVT protection, a subset of chicks were bursectomized and these birds plus controls were similarly vaccinated and challenged, and the levels of vaccinal protection determined. Results The efficacy of bivalent SB-1'+'HVT surpasses that of either SB-1 or HVT monovalent vaccines in controlling the level of pathogenic MDV in PBMCs until the end of the study, and this correlated with the ability to inhibit tumor formation. SB-1 replication in the spleen increased from 1 to 14 DPC, while HVT replicated only in the bursa at 1 DPC. The bursa was necessary for immune protection induced by HVT vaccine. Conclusion Synergy of SB-1 and HVT vaccines is due to additive influences of the individual vaccines acting at different times and target organs. And the bursa is vital for HVT to replicate and induce immune protection.