Genetics and vaccine efficacy: Host genetic variation affecting Marek’s disease vaccine efficacy in White Leghorn chickens

Abstract

Marek's disease (MD) is a T-cell lymphoma disease of domestic chickens induced by MD virus (MDV), a naturally oncogenic and highly contagious cell-associated α-herpesvirus. Earlier reports have shown that the MHC haplotype as well as non-MHC genes are responsible for genetic resistance to MD. The MHC was also shown to affect efficiency of vaccine response. Using specific-pathogen-free chickens from a series of 19 recombinant congenic strains and their 2 progenitor lines (lines 6(3) and 7(2)), vaccine challenge experiments were conducted to examine the effect of host genetic variation on vaccine efficacy. The 21 inbred lines of White Leghorns share the same B*2 MHC haplotype and the genome of each recombinant congenic strain differs by a random 1/8 sample of the susceptible donor line (7(2)) genome. Chickens from each of the lines were divided into 2 groups. One was vaccinated with turkey herpesvirus strain FC126 at the day of hatch and the other was treated as a nonvaccinated control. Chickens of both groups were inoculated with a very virulent plus strain of MDV on the fifth day posthatch. Analyses of the MD data showed that the genetic line significantly influenced MD incidence and days of survival post-MDV infection after vaccination of chickens (P<0.01). The protective indices against MD varied greatly among the lines with a range of 0 up to 84%. This is the first evidence that non-MHC host genetic variation significantly affects MD vaccine efficacy in chickens in a designed prospective study.

Genomic Variation between Genetic Lines of White Leghorns Differed in Resistance to Marek’s Disease

“…Some of these have been well investigated and reported [23][24][25][26][54][55][56]. We recently showed non-MHC genetic variation, in addition to MHC B haplotype that was primarily reported by Bacon and Witter in the 1990s [23][24][25][26]57], also plays an important role in modulating MD vaccine efficacy [31][32][33]. The findings of MHC and non-MHC effects on MD vaccine protective efficacy are in good agreement with reports of studies both in humans and other animals [58,59].…”

“…Each RCS was then established by sib-mating. Therefore, on average each RCS theoretically possesses 1/8 random line 7 2 genome and 7/8 line 6 3 genome [31]. All RCS share the same MHC B*2 haplotype.…”

“…The lines 6 3 and 7 2 carry MHC B*2 haplotype [43]. The RCS were developed from the lines 6 3 and 7 2 as previously described [31,40]. Briefly, lines 6 3 and 7 2 were crossed followed by two consecutive backcrosses to the donor line 6 3 .…”

“…Our data also showed for the first time there may be a chicken line by vaccine interaction modulating MD vaccine protective efficacy. We further hypothesized that vaccine protective efficacy, which reportedly depends on many factors, including vaccine dosage, number of vaccinations, age at vaccination, the time interval between vaccination and infection, maternal antibody, type of vaccine, and host genetics, is also partially determined by interactions among vaccine virus genome, host genome, as well as the challenging virus genome [31][32][33]. Based on the above findings our long-term goal is to determine what are the genetic and epigenetic differences between the genetic lines of chickens that modulate the differential protective efficacy of MD vaccines against vv+ MDV challenge when the other factors listed above are similar or identical.…”

Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic <b><i>Gallid alphaherpesvirus 2</i></b> Telomere Integration in Host Birds

“…MD vaccination strategies commonly consist of monovalent injection of herpesvirus of turkey (HVT, apathogenic MDV serotype 3) or polyvalent injections of HVT [Churchill et al, 1969;Okazaki et al, 1970;Kingham et al, 2001], SB-1 (apathogenic MDV serotype 2) [Schat and Calnek, 1978;Spatz and Schat, 2011], or Rispens/CV1988 (attenuated MDV serotype 1) [Rispens et al, 1972;Calnek et al, 1983;Petherbridge et al, 2003;Spatz et al, 2007]. The MD vaccines protect birds against disease progression and lymphoma development induced with oncogenic strains [Chang et al, 2010;Haq et al, 2010] through non-sterilizing immunity [Nair, 2005] in both susceptible and resistant host birds. The genomes of these strains are highly similar to the oncogenic strains, but crucial differences exist .…”