The Emergence of a vv + MDV Can Break through the Protections Provided by the Current Vaccines

Abstract

Marek’s disease (MD) is an infectious malignant T-cell lymphoma proliferative disease caused by Marek’s disease virus (MDV). In recent years, the emergence of very virulent (vv) and/or very virulent plus (vv +) strains of MDV in the field has been suggested as one of the causes of vaccination failure. The pathogenicity of the MDV strain GX18NNM4, isolated from a clinical outbreak in a broiler breeder flock that was vaccinated with CVI988/Rispens, was investigated. In the vaccination-challenge test, GX18NNM4 was able to break through the protections provided by the vaccines CVI988 and 814. It also significantly reduced body weight gain and caused marked gross lesions and a large area of infiltration of neoplastic lymphocyte cells in the heart, liver, pancreas, etc. of the infected birds. In addition, the expressions of programmed death 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1), in the spleens and cecal tonsils (CTs) of the unvaccinated challenged birds were significantly increased compared to those in the vaccinated challenged birds, indicating that the PD-1/PD-L1 pathway is related to immune evasion mechanisms. The results showed that the GX18NNM4 strain could cause severe immunosuppression and significantly decrease the protections provided by the current commercial vaccines, thus showing GX18NNM4 to be a vv + MDV strain.

An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens

“…However, to date, the mechanisms by which protective immunity is elicited in response to MD vaccines have not been fully revealed ( 11 ). In recent years, very virulent plus MDV field strains emerged and broke through the protection elicited by the MD vaccines clinically or experimentally ( 12 – 15 ), highlighting a need for a more efficacious vaccine than CVI988 to combat increasingly virulent MDV strains in the future. However, most of the MD vaccines under development are neither better nor safer than CVI988 ( 16 , 17 ).…”

Analysis of the evolution and transmission dynamics of the field MDV in China during the years 1995–2020, indicating the emergence of a unique cluster with the molecular characteristics of vv+ MDV that has become endemic in southern China

“…Y. Shi et al, 2020). Therefore, understanding the epidemiology and the molecular changes of the field strains has significant applied relevance for the industry.…”

“…Isolates obtained from vaccinated flocks indicated that the vaccines were not capable of providing complete protection for the flocks and that the emergence of variant viruses was a possible reason for the vaccination failures (M. Y. Shi et al, 2020;Y. P. Zhang et al, 2015).…”

“…A88T and Q93R) might result from the immune pressure (M. Y. Shi et al, 2020) and are likely to become the dominant MDV strains endemic in southern China and possibly even in northern China in future years.…”

“…Our recent study showed one of the strains GX18NNM4 was identified as vv+ MDV (M. Y. Shi et al, 2020). Thus, a unique sub-cluster of Group C isolates (97.4%, 38/39) that were obtained from the Southern Region during the most recent years 2017-2020 (Figures 1 and 2), not only had the molecular characteristics of vv+ MDV strains, but also had the specific substitutions of A88T and Q93R together in nearly half of these strains (44%, 17/39).…”