Cell culture attenuation eliminates rMd5ΔMeq-induced bursal and thymic atrophy and renders the mutant virus as an effective and safe vaccine against Marek's disease.
Marek's disease virus (MDV) encodes a basic leucine zipper oncoprotein, Meq, which structurally resembles jun/fos family of transcriptional activators. It has been clearly demonstrated that deletion of Meq results in loss of transformation and oncogenic capacity of MDV. The rMd5ΔMeq virus provided superior protection than CVI988/Rispens vaccine in 15×7 chickens when challenged with a very virulent plus (vv+) strain of MDV, 648A. The rMd5ΔMeq construct was also shown to be an effective vaccine in commercial chickens that were challenged under field conditions by exposure to seeder chicken inoculated with MDV strain 686, a vv+ and arguably the most pathogenic strain of MDV. Although deletion of Meq gene renders the virus non-oncogenic, it still induces lymphoid organ atrophy like that of the parental rMd5, in highly susceptible MDV maternal antibody negative (MAb-) chickens. We have generated 50 cell culture passages of attenuated rMd5ΔMeq viruses and found no significant lymphoid organ atrophy beginning at 40(th) passage onward when compared with the normal control chickens. The protective ability of these attenuated Meq null viruses against challenge with vv+ MDV strain 686 is similar to the original virus at 19(th) passage in maternal antibody negative chickens. The data indicate that attenuation of these Meq null viruses has no influence on their protective efficacy, but eliminated lymphoid organ atrophy and rendered them safe to use even in MAb- chickens, a characteristic that should facilitate commercialization and licensing by vaccine manufacturers.
United States Department of Agriculture, Agricultural Research Service, Avian Disease and Oncology Laboratory, East Lansing, MI 48823,United States. leelu@msu.edu
Lucy F
LF
Lee
Mohammad
M
Heidari
Huanmin
H
Zhang
Blanca
B
Lupiani
Sanjay M
SM
Reddy
Aly
A
Fadly
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002060:Bursa of Fabricius / Q000276:immunology / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D002645:Chickens / Q000276:immunology / Q000821:virology; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D016679:Genome, Viral; D007150:Immunohistochemistry; D008297:Male; D008380:Marek Disease / Q000276:immunology / Q000628:therapy* / Q000821:virology; D022501:Marek Disease Vaccines / Q000235:genetics / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009929:Organ Size; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology / Q000821:virology*; D014775:Virus Activation; D014776:Virus Cultivation / Q000379:methods
D000914:Antibodies, Viral; D022501:Marek Disease Vaccines; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins