Marek's disease virus (MDV) is an oncogenic alphaherpesvirus and the causative agent of
Marek's disease (MD), characterized by immunosuppression,
paralysis, nerve enlargement and induction of
T-cell lymphomas in chickens. Despite widespread usage of
vaccines since the 1970s to control MD, more virulent field strains of MDV have emerged that overcome vaccinal protection, necessitating the development of new and more protective MD
vaccines. The ∆Meq virus, a recombinant Md5 strain MDV lacking the viral oncogene Meq, is one candidate MD
vaccine with great potential but unfortunately it also causes bursal-thymic
atrophy (BTA) in maternal antibody negative chickens, raising concerns that impede commercial use as a
vaccine. Previously, we identified a point mutation within UL5 that reduced in vivo replication in attenuated viruses. We proposed that introduction of the UL5 point mutation into the ∆Meq virus would reduce in vivo replication and eliminate BTA yet potentially retain high protective abilities. In birds, the ∆Meq+UL5 recombinant MDV had reduced replication compared to the original ∆Meq virus, while weights of lymphoid organs indicated that ∆Meq+UL5 did not induce BTA, supporting the hypothesis that reduction of in vivo replication would also abolish BTA.
Vaccine trials of the ∆Meq+UL5 virus compared to other ∆Meq-based viruses and commercial
vaccines show that, while the ∆Meq+UL5 does provide vaccinal protection, this protection was also reduced compared to the original ∆Meq virus. Therefore, it appears that a very delicate balance is required between levels of replication able to induce high vaccinal protection, yet not so high as to induce BTA.