Location: Endemic Poultry Viral Diseases ResearchTitle: Vaccinal efficacy of molecularly cloned Gallid alphaherpesvirus 3 strain 301B/1 against very virulent Marek’s disease virus challenge
Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/10/2020
Publication Date: 3/5/2020
Citation: Kim, T.N., Spatz, S.J., Dunn, J.R. 2020. Vaccinal efficacy of molecularly cloned Gallid alphaherpesvirus 3 strain 301B/1 against very virulent Marek’s disease virus challenge. Journal of General Virology. 101(5):542-552. https://doi.org/10.1099/jgv.0.001403.
Interpretive Summary: Marek’s disease is a highly contagious lymphoproliferative disease of chickens. Marek’s disease virus has evolved its virulence partly because of imperfect vaccines and faulty administration. Turkey herpesvirus (HVT) and Gallid alphaherpesvirus 3 (GaHV-3) have been developed as bivalent vaccines to improve upon the level of protection elicited by single formulations of HVT or GaHV-3 (e.g. SB-1 vaccine strain). Since the in vitro passage of MD vaccine strains can result in over attenuation, we sought to secure a molecularly defined MDV vaccine strain by inserting the mini-F replicon into the genome of another GaHV-3 strain (301B/1) thus creating a bacterial artificial chromosome (BAC). Infectious virus was rescued from various 301B/1-BAC clones by reverse genetics techniques. Reconstituted 301B/1-BAC viruses showed growth kinetics comparable to that of the parental 301B/1 virus. Data from a vaccine protection study using specific-pathogen-free chickens suggest vaccine virus reconstituted from a selected GaHV-3 301B/1 BAC exhibited an efficacious protection profile against very virulent MDV challenge.
Technical Abstract: Marek’s disease virus (MDV), a causative agent of Marek’s disease, has evolved its virulence partly because the current control strategies fail to provide sterilizing immunity. Gallid alphaherpesvirus 3 (GaHV-3) and turkey herpesvirus have been developed as bivalent vaccines to improve upon the level of protection elicited by single formulations. Since the in vitro passage of vaccines can result in attenuation, a GaHV-3 strain 301B/1 was cloned as a bacterial artificial chromosome (BAC) by inserting the mini-F replicon into the virus genome. A fully infectious virus, v301B-BAC, was reconstituted from the 301B/1 BAC clone and had similar growth kinetics comparable to that of the parental 301B/1 virus with strong reactivity against anti-301B/ 1 chicken sera. Protective efficacies of v301B-BAC, parental 301B/1, and SB-1 vaccine were evaluated against a very virulent MDV Md5 challenge. Clinical signs were significantly lower in the v301B-BAC vaccinated groups (24–25%), parental 301B/1 (29%) compare to that of non-vaccinated control (100%) and the removal of BAC sequences from v301B-BAC genome further reduced this to 17%. The protective indices of v301B-BACs (75–76%) were comparable with those of both the 301B/1 and the SB-1 vaccine (71%). Removal of the mini-F replicon resulted in a reconstituted virus with a protective index of 83%. The shedding of challenge virus was notably lower in the v301B-BAC, and v301B-delBAC vaccinated groups. Overall, the protective efficacy of the 301B-BAC- derived vaccine virus against a very virulent MDV challenge was comparable to that of the parental 301B/1 virus as well as the SB-1 vaccine virus.