Location: Avian Disease and Oncology ResearchTitle: Addition of a UL5 helicase-primase subunit point mutation eliminates bursal-thymic atrophy of Marek’s disease virus delta-Meq recombinant virus but reduces vaccinal protection
Submitted to: Avian Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2015
Publication Date: 8/14/2015
Publication URL: http://handle.nal.usda.gov/10113/61282
Citation: Hildebrandt, E., Dunn, J.R., Cheng, H.H. 2015. Addition of a UL5 helicase-primase subunit point mutation eliminates bursal-thymic atrophy of Marek’s disease virus delta-Meq recombinant virus but reduces vaccinal protection. Avian Pathology. 44(4):254-258.
Interpretive Summary: Marek’s disease (MD) is a T cell lymphoma of chickens caused by the highly oncogenic Marek’s disease virus (MDV), and is currently controlled by vaccines though there is a need to develop new and more effective vaccines to combat more virulent field strains. The delta-Meq virus is a top candidate MD vaccine but, unfortunately, it also induces atrophy of immune organs in certain birds inhibiting commercial approval. In this study, we evaluated whether additional of another viral mutation associated with attenuation would alleviate this atrophy. Our results showed that this double recombinant MDV virus did not cause atrophy as intended but the protective efficiency was also reduced. This suggests that there is a delicate balance between viral replication that induced atrophy in immune organs and the ability to provide vaccinal protection. This knowledge is important for scientists and biologic companies that are trying to develop improved rationally designed MD vaccines.
Technical Abstract: Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus and the causative agent of Marek’s disease (MD), a T-cell lymphoma of chickens. Despite widespread usage of vaccines since the 1970’s 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 delta-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, inhibiting 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 delta-Meq virus would reduce in vivo replication and eliminate BTA yet potentially retain high protective abilities. In birds, the delta-Meq+UL5 recombinant MDV had reduced replication compared to the original delta-Meq virus, while weights of lymphoid organs indicated that delta-Meq+UL5 did not induce BTA, supporting the hypothesis that reduction of in vivo replication would also abolish BTA. Vaccine trials of the delta-Meq+UL5 virus compared to other delta-Meq-based viruses and commercial vaccines show that, while the delta-Meq+UL5 does provide vaccinal protection, this protection was also reduced compared to the original delta-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.