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

Vaccine. 2019 Oct 8;37(43):6397-6404. doi: 10.1016/j.vaccine.2019.09.003. Epub 2019 Sep 9.

Abstract

Background: Marek's disease (MD) is a lymphoproliferative disease of chickens caused by Marek's disease virus (MDV), an oncogenic α-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.

Keywords: Bivalent vaccine; Bursa; Marek’s disease; Marek’s disease virus; Protective synergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chickens / immunology
  • Drug Synergism
  • Herpesvirus 1, Meleagrid / immunology
  • Herpesvirus 2, Gallid / immunology
  • Herpesvirus 2, Gallid / physiology
  • Leukocytes, Mononuclear / virology
  • Lymphoid Tissue / virology
  • Lymphoma / prevention & control
  • Lymphoma / veterinary*
  • Lymphoma / virology
  • Marek Disease Vaccines / administration & dosage
  • Marek Disease Vaccines / immunology*
  • Peritoneal Cavity / virology
  • Poultry Diseases / prevention & control*
  • Poultry Diseases / virology
  • Vaccination / veterinary*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*
  • Virus Replication

Substances

  • Marek Disease Vaccines
  • Viral Vaccines