A Novel Effective and Safe Vaccine for Prevention of Marek's Disease Caused by Infection with a Very Virulent Plus (vv+) Marek's Disease Virus.

Yifei Liao,Aijun Sun,Owais A Khan,Blanca Lupiani,Sanjay M Reddy

doi:10.3390/vaccines9020159

Yifei Liao, Aijun Sun + Show 3 more

Open Access

https://doi.org/10.3390/vaccines9020159

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Journal: Vaccines	Publication Date: Feb 16, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Texas A&M University, Henan Agricultural University

Abstract

Marek’s disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset lymphoma in chickens. Marek’s disease (MD) is effectively controlled using vaccination; however, MDV continues to break through vaccinal immunity, due to the emergence of highly virulent field strains. Earlier studies revealed that deletion of the meq gene from MDV resulted in an attenuated virus that protects against MD in chickens challenged with highly virulent field strains. However, the meq deleted virus retains the ability to induce significant lymphoid organ atrophy. In a different study, we found that the deletion of the vIL8 gene resulted in the loss of lymphoid organ atrophy in inoculated chickens. Here, we describe the generation of a recombinant MDV from which both meq and vIL8 genes were deleted. In vitro studies revealed that the meq and vIL8 double deletion virus replicated at levels similar to the parental very virulent plus (vv+) virus. In addition, in vivo studies showed that the double deletion mutant virus (686BAC-ΔMeqΔvIL8) conferred protection comparable to CVI988, a commercial vaccine strain, when challenged with a vv+ MDV virus, and significantly reduced lymphoid organ atrophy, when compared to meq null virus, in chickens. In conclusion, our study describes the development of a safe and effective vaccine candidate for prevention of MD in chickens.

Highlights

Marek’s disease (MD) is caused by the highly contagious Marek’s disease virus (MDV)and is characterized by immunosuppression, neurological disease, and rapid onset of T cell lymphoma in visceral organs and skin [1,2,3]
Fragment corresponding to the Viral interleukin-8 (vIL8) gene in 686BAC is 9476 bp, which is reduced to 8798 bp in 686BAC-∆vIL8
Digestion of 686BAC∆Meq∆vIL8 with EcoRI resulted in 8798 bp and 1439 bp fragments (*)

Summary

Introduction

Marek’s disease (MD) is caused by the highly contagious Marek’s disease virus (MDV)and is characterized by immunosuppression, neurological disease, and rapid onset of T cell lymphoma in visceral organs and skin [1,2,3]. There are three highly related species within the Mardivirus genus: MDV type 1 (MDV-1, known as Gallid alphaherpesvirus 2, GaHV-2) includes pathogenic strains and their derivatives; MDV type 2 (MDV-2 or GaHV-3). MD is the first tumor disease that has been successfully controlled using vaccination [6], and strains from MDV-1 (refers to MDV in following text), MDV-2, and HVT have been used as vaccines to protect against MD [3,7,8]. An MDV cell culture passage attenuated viral strain, HPRS-16/att, was first used to protect chickens against challenge with v MDV strains [9]. In the early 1990s, emergence of vv+ field strains resulted in the introduction, in the United States, of CVI988/Rispens, a cell culture passage attenuated MDV virus and the gold standard among MD vaccines [13,14]. To increase the replication and vaccine efficacy of CVI988, a novel chimeric vaccine, CVRM (Prevexxion RN, Boehringer Ingelheim), was generated by inserting the reticuloendotheliosis (REV) long terminal repeat (LTR) into the CVI988 genome and is currently commercially available [15]

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