Marek's disease virus (MDV) is an oncogenic herpesvirus that causes various clinical syndromes in its natural host, the chicken. MDV has long been of interest as a model organism, particularly with respect to the pathogenesis and immune control of virus-induced lymphoma in an easily accessible small-animal system. Recent advances in MDV genetics and the determination of the chicken genome sequence, aided by functional genomics, have begun to dramatically increase our understanding not only of lytic MDV replication, but also of the factors and mechanisms leading to latency and tumour formation. This new information is helping to elucidate cellular signalling pathways that have undergone convergent evolution and are perturbed by different viruses, and emphasizes the value of MDV as a comparative biomedical model. Furthermore, the door is now open for rational and efficient engineering of new vaccines against one of the most important and widespread infectious diseases in chickens.

Marek's disease virus: from miasma to model

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This chapter discusses the epidemiology of Marek's disease (MD). The major causes of MD outbreaks are improper handling of the vaccines, unhygienic conditions, influence of other pathogens that cause immunosuppressive effects, stressful situations, and the evolution of new Marek's disease virus (MDV) variants. After introduction of the first group of MD vaccines—such as the serotype 3 herpesvirus of turkeys (HVT) vaccine—field problems from MD appeared to be controlled. The CVI988 (Rispens) vaccine was certainly the savior of poultry industries worldwide during the 1990s. Although the infection decreased in the vaccinated birds, the vaccine was not capable of inducing immune responses that protected against infection and shedding. Consequently, there was a presence of a continuous virus reservoir in these flocks. The other approach for preventing MD problems is the introduction of best practice at all stages of the production process. Such practices include (1) auditing of the storage, (2) reconstitution and administration of the vaccines, (3) implementation of standard operating procedures for various methods, (4) checking the compatibility of additives to the MD vaccines, and (5) the use of coloring dyes while administering vaccines to confirm vaccine uptake. Currently, no major MD problems appear to be uncontrolled with existing technologies around the world.

5 – Marek's disease: A worldwide problem

Marek's disease vaccines: a solution for today but a worry for tomorrow?

For the past 30 years, the poultry industry has relied on a series of avirulent or attenuated live virus vaccines to provide protection to young chickens against natural challenge with field strains of Marek’s disease (MD). This strategy has been unusually effective. In the United States, losses from the condemnation at slaughter of young broiler chickens with visible lesions of MD have decreased from 1.5% in 1970 to 0.0121% in 1999, a reduction of over 99% (Fig. 1). Even more dramatic reductions are evident in Georgia and Delaware, states with intensive broiler production. Similar benefits have been realized in commercial layer and breeder flocks. Vaccination for the control of MD in the field has been one of the great successes in veterinary medicine.

Protective efficacy of Marek's disease vaccines.

Recombinant strains of herpesvirus of turkeys (HVT) were constructed that contain either the fusion protein gene or the hemagglutinin-neuraminidase gene of Newcastle disease virus (NDV) inserted into a nonessential gene of HVT. Expression of the NDV antigens was regulated from a strong promoter element derived from the Rous sarcoma virus long terminal repeat. Recombinant HVT strains were stable and fully infectious in cell culture and in chickens. Chickens receiving a single intra-abdominal inoculation at 1 day of age with recombinant HVT expressing the NDV fusion protein had an immunological response and were protected (> 90%) against lethal intramuscular challenge at 28 days of age with the neurotropic velogenic NDV strain Texas GB. Recombinant HVT expressing the NDV hemagglutinin-neuraminidase provided partial protection (47%) against the same challenge. Chickens vaccinated with recombinant HVT vaccines had low levels of protection against NDV replication in the trachea when challenged ocularly. Recombinant HVT vaccines and the parent HVT strain provided similar levels of protection to chickens challenged with the very virulent RB1B strain of Marek's disease virus, indicating that insertion of foreign sequences into the HVT genome did not compromise the ability of HVT to protect against Marek's disease.

https://www.jstor.org/stable/pdfplus/1591544.pdf

Protection of Chickens From Newcastle and Marek's Diseases With a Recombinant Herpesvirus of Turkeys Vaccine Expressing the Newcastle Disease Virus Fusion Protein

A Marek's disease virus of low pathogenicity was isolated from a flock of chickens and was designated strain CVI 988. On primary isolation, this virus did not cause disease in susceptible chicks and gave excellent protection on subsequent challenge with a virulent virus, even if this challenge was performed shortly after vaccination. The virus occasionally caused minor microscopic lesions in antibody-free MD susceptible chicks but on further passage in DEF cultures the virus became completely avirulent while retaining its A antigen, spreading capacity and immunizing potentials. Chicks vaccinated by contact exposure developed a high degree of MD resistance after the 5th week but immunity was induced more rapidly when 3-week-old seeder chicks, which were actively shedding vaccine virus, were used as the source of exposure. However, by any procedure, contact-vaccinated chicks required several weeks for the development of solid immunity. High passage virus did not become virulent after 5 subsequent passages in antibody-free MD susceptible chicks. Vaccinated birds produced antibody which remained at a high level through observation periods of 2 years. Viremia and virus-shedding persisted throughout this period in a considerable number of birds. Rhesus monkeys inoculated with the virus did not develop any lesions during a one year observation period and no seroconversion could be detected.

Control of Marek's disease in the Netherlands. I. Isolation of an avirulent Marek's disease virus (strain CVI 988) and its use in laboratory vaccination trials.

Maas Hj

Papers

Control of Marek's disease in the Netherlands. I. Isolation of an avirulent Marek's disease virus (strain CVI 988) and its use in laboratory vaccination trials.