Codon deoptimization of UL54 in meq-deleted Marek's disease vaccine candidate eliminates lymphoid atrophy but reduces vaccinal protection

Authors: Conrad, Steven; Hearn, Cari; SILVA, ROBERT - Retired ARS Employee; Dunn, John

Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2020
Publication Date: 1/13/2020
Citation: Conrad, S.J., Hearn, C.J., Silva, R.F., Dunn, J.R. 2020. Codon deoptimization of UL54 in meq-deleted Marek's disease vaccine candidate eliminates lymphoid atrophy but reduces vaccinal protection. Avian Diseases. 64(3):243-246. https://doi.org/10.1637/aviandiseases-D-19-00166.
DOI: https://doi.org/10.1637/aviandiseases-D-19-00166

Interpretive Summary: There is a continuing need for new vaccines to protect poultry (chickens) from Marek's disease (MD), a debilitating disease caused by a virus named Marek's disease virus (MDV). Recently it has been shown that live attenuated vaccines in which a particular gene in the MDV genome, meq, is deleted, are indeed protective against MD in chickens. A problem is that although protective, these vaccines cause significant atrophy of the lymphoid organs, the bursa and the thymus (hence the term "bursa and thymus atrophy"," or BTA). We reasoned that attenuation of the meq-negative MDV by codon deoptimization of another viral gene, UL54, might prevent BTA in immunized chickens. We show that, while this is indeed the case, animals immunized with the meq-negative MDV are not sufficiently protected against infection with wild type MDV.

Technical Abstract: Marek’s disease (MD) is a highly-contagious and oncogenic disease of chickens. Its etiologic agent is the alphaherpesvirus Marek’s disease virus (MDV), and it is a chronic and ubiquitous problem for the poultry industry with significant economic impact in both the United States and worldwide. We have previously demonstrated that codon pair deoptimization of the UL54 gene results in reduced gene product accumulation in vitro, with reduced viral genome copy number upon infection and reduced atrophy of bursa and thymus (BTA) in vivo as well. In this report we detail our attempts to use the same strategy on a meq-deleted MDV mutant. Unlike the wild type virus, MDV deleted for the meq gene is no longer oncogenic, but infected birds experience an unacceptable amount of bursa and thymus atrophy (BTA). We produced a meq-deleted MDV with a dicodon-deoptimized UL54 and tested its ability to cause BTA and to serve as a protective vaccine. We found that while the dicodon-deoptimized UL54 meq-negative virus does indeed cause less BTA than the meq-negative parental virus, the degree of vaccinal protection conferred by the meq-negative, dicodon-deoptimized UL54 virus is also less that that conferred by the parental virus.