Prevention of Marek's disease: a review.

Marek's disease (MD) is a highly infectious neoplastic condition of chickens caused by a herpesvirus. The virus is cell associated in tumors and in all organs except in the feather follicle where enveloped infectious virions egress from the body. From this source, infection is spread horizontally by the airborne route to the environment and to other chickens. Vertical transmission from dam to offspring does not occur or at best is very rare. The nonpathogenic herpesvirus of turkeys (HTV) is ubiquitous in turkeys and is probably spread horizontally by the airborne route. When chickens are inoculated with this virus, they do not subsequently develop MD even after infection with virulent Marek's disease virus. The Marek's disease virus, not the HVT, will spread horizontally from dually infected birds. The HVT vaccine is safe and highly effective in preventing MD under field conditions, and most chickens throughout the world are vaccinated with this vaccine. Other vaccines that have been used but have disadvantages over HVT include the following: (a) the highly pathogenic HPRS 16 strain of Marek's disease virus was attenuated by passage in cell culture. The attenuated virus protects against MD and does not spread, but "over-attenuated" virus does not protect; (b) naturally apathogenic strains virologically, immunologically, and epizootiologically similar to pathogenic strains will protect when adminstered before infection with the virulent strains; (c) virus preparations that have been chemically treated to inactivate infectivity protect only slightly. When a candidate vaccine virus for the prevention of herpesvirus-induced cancer in humans is developed, the purity of the vaccine preparations will be easily determined by modern techniques. However, measurements of safety and effectiveness are a significant problem. If, analogous to the MD model, the vaccine will have to be administered shortly after birth and the incubation period to development of neoplasms is long, then pathogenicity tests in nonhuman primates and other animals may be of limited valued. However, biochemical demonstration that the segment of the nucleic acid responsible for oncogenesis is absent from the vaccine virus may be the major indication that the vaccine is nonocogenic and therefore safe. Because of the low incidence of neoplasia and long incubation period, the effectiveness of the vaccine will be difficult to test. The vaccine possibly will protect against an acute manifestation of viral infection. Future research on MD will be directed to determining the mechanism of protection against disease, i.e., whether immunity is mediated by thymus- or bursa-dependent systems, and to identifying the protective antigen, i.e., which cell surface or an interior antigen induces the protective immunity. The prevention of MD by vaccination may become a very fruitful area for model studies on prevention of human cancer by vaccination.