History of the First-Generation Marek's Disease Vaccines: The Science and Little-Known Facts.

Shortly after the isolation of Marek's disease (MD) herpesvirus (MDV) in the late 1960s vaccines were developed in England, the United States, and The Netherlands. Biggs and associates at the Houghton Poultry Research Station (HPRS) in England attenuated HPRS-16, the first cell-culture-isolated MDV strain, by passaging HPRS-16 in chick kidney cells. Although HPRS-16/Att was the first commercially available vaccine, it never became widely used and was soon replaced by the FC126 strain of herpesvirus of turkeys (HVT) vaccine developed by Witter and associates at the Regional Poultry Research Laboratory (now Avian Disease and Oncology Laboratory [ADOL]) in East Lansing, MI. Ironically, Kawamura et al. isolated a herpesvirus from kidney cell cultures from turkeys in 1969 but never realized its potential as a vaccine against MD. Rispens of the Central Veterinary Institute (CVI) developed the third vaccine. His associate, Maas, had found commercial flocks of chickens with MDV antibodies but without MD. Subsequently, Rispens isolated a very low pathogenic strain from hen number 988 from his MD antibody-positive flock, which was free of avian leukosis virus and clinical MD. This isolate became the CVI-988 vaccine used mostly in The Netherlands. During the late 1970s, HVT was no longer fully protective against some new emerging field strains. The addition of SB-1, isolated by Schat and Calnek, to HVT improved protection against the emerging very virulent strains. In the 1990s CVI-988 became the worldwide vaccine gold standard. This review will present data from published papers and personal communications providing additional information about the exciting 15-yr period after the isolation of MDV to the development of the different vaccines.

Use of Marek's disease vaccines: could they be driving the virus to increasing virulence?

Marek's disease (MD) is an economically important neoplastic disease of poultry. MD almost devastated the poultry industry in the 1960s but the disease was brought under control after Marek's disease herpesvirus (MDV) was identified and vaccines were developed. This is the first effective use of an antiviral vaccination to prevent a naturally occurring cancer in any species. MDV infection has many effects. Initially causing a cytolytic infection in B-lymphocytes, MDV infects activated T-lymphocytes where it becomes latent. In susceptible chicken genotypes MDV transforms CD4+ lymphocytes, causing visceral lymphomas and/or neural lesions and paralysis. Fully productive infection and shedding of infectious virus only occurs in the feather-follicle epithelium. Vaccination of newly-hatched chicks with live vaccines has been widely used to successfully control MD since the early 1970s. However, vaccinated chickens still become infected and shed MDV. Vaccine breaks have occurred with regularity and there is evidence that the use of MD vaccines could be driving MDV to greater virulence. MD continues to be a threat and a number of strategies have been adopted such as the use of more potent vaccines and vaccination of the embryonic stage to provide earlier protection. Recombinant MD vaccines are useful vectors and are being exploited to carry both viral and host genes to enhance protective immune responses. The future aim must be to develop a sustainable vaccine strategy that does not drive MDV to increased virulence.