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.

Keywords: Marek’s disease virus; immunosuppression; pathogenicity analysis; protection index; vv + MDV.

Figure 1

Statistics of body weight of experimental birds (X ± SD). Means not sharing a common letter are significantly different (p < 0.05).

Figure 2

Dynamics of immune organ indices of the experimental birds. (A) spleen; (B) thymus; (C) bursa. Means not sharing a common letter are significantly different (p < 0.05).

Figure 3

The viral load of MDV in the peripheral blood lymphocytes (PBLs) of the experimental birds. Means not sharing a common letter are significantly different (p < 0.05).

Figure 4

The mRNA expressions of PD-1 and PD-L1 in the tissues from birds experimentally infected with MDV. (A) PD-1 in the spleen; (B) PD-1 in the cecal tonsils; (C) PD-L1 in the spleen; (D) PD-L1 in the cecal tonsils. Determined by real-time PCR. Means not sharing a common letter are significantly different (p < 0.05).

Figure 5

Survival patterns showing the overall effects of the various treatments.

Figure 6

Anatomical and histological lesions: (A,L) white solid nodules in the lungs; (E,P) numerous proliferating tumor cells concentrated in the lung tissue; (B,D,J) tumor or tumor-like lesions in the heart; (F,H,N) numerous infiltrations of diffuse lymphocytosis in myocardial fibers; (C) pancreas hemorrhage with tumor; (G) numerous lymphocytosis proliferations in pancreas; (I) white tumor nodules, approximately 1–3 mm in diameter, on the liver surface; (M) numerous proliferating tumor cells were concentrated in the hepatic tissue; (K) white tumor nodule on the surface of spleen; (O) large number of lymphocytes infiltrated in the spleen tissue.