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Title: SEROTYPE 1 VIRUSES MODIFIED BY BACKPASSAGE OR INSERTIONAL MUTAGENESIS: APPROACHING THE THRESHOLD OF VACCINE EFFICACY IN MAREK'S DISEASE

Author
item Witter, Richard
item KREAGER, K - HY-LINE INTERNATIONAL

Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/7/2004
Publication Date: 12/31/2004
Citation: Witter, R.L., Kreager, K.S. 2004. Serotype 1 viruses modified by backpassage or insertional mutagenesis: approaching the threshold of vaccine efficacy in Marek's disease. Avian Diseases. 48:768-782.

Interpretive Summary: Marek's disease (MD), a virus-induced cancer-like disease of chickens, is considered as a major disease problem in commercial poultry. Vaccination has dramatically reduced the incidence of the disease, but efforts to developed improved vaccines have met with limited success in the past.The objective of this research was to determine the feasibility of developing highly protective vaccines against MD. We have determined that two vaccines developed in this study are highly protective, but are not superior to existing commercial products. In fact, there is evidence for a threshold of vaccine efficacy that may be difficult to exceed. This important information will help scientists in academia and industry understand the prospects for improved MD vaccines and eventually lead to better control of the disease.

Technical Abstract: Studies were conducted to evaluate strategies for deriving Marek's disease (MD) vaccines of very high protective efficacy, irrespective of virulence. Candidate viruses from parent strains representing v and vv+ pathotypes were modified by cell culture passage, backpassage in chickens, or insertional mutagenesis following co-cultivation with retroviruses. Modified strains were also evaluated for the ability to induce lymphomas or other pathological changes in ab+ and antibody negative (ab-) chickens. Two of the 10 modified viruses, strains RM1 and CVI988/BP5, provided high levels of protection against highly virulent MDV challenge. Three of the strains, including RM1 and CVI988/BP5, induced lymphoid organ atrophy in ab- chicks but not in ab+ commercial chicks, a property designated here as L phenotype. Seven strains, including two of the L+ strains, were mildly oncogenic for ab- chicks; 5 of these strains caused no tumors in ab+ chickens, a property designated here as O phenotype. The two fully attenuated strains induced neither lymphomas nor lymphoid organ atrophy. These findings suggest that new virus strains with high levels of protective immunity comparable to that of CVI988 can be developed. However, the question of whether strains can be developed that exceed the efficacy of current CVI988-based vaccines remains unanswered.