Assessment Of Non-MHC Host Genetic Variation Effects On Marek's Disease Vaccine Efficacy

MD is a T cell lymphoma disease of domestic chickens induced by Marek's disease viruses (MDV), a naturally oncogenic and highly contagious cell-associateda-herpesvirus. MD is characterized by a mononuclear cellular infiltration of the peripheral nerves, gonads, iris, various viscera, muscles, and the skin. Partial or complete paralysis is a fairly common symptom of MD due to accumulation and proliferation of tumor cells in peripheral nerves. Since the 1970s, MD has been controlled by vaccination and improvement in animal husbandry. However, even with vaccination, the annual losses due to bird condemnation and reduced egg production well exceed $160 million in the U.S. alone. This is an estimate reported two decades ago. Therefore, inflation, new disease outbreaks, or MDV-induced immuno suppress ion since then are not accounted for. Although vaccine prevents the formation of lymphoma and other MD symptoms, it does not prevent MDV infection, replication, or horizontal spread. Moreover, while currently available commercial vaccines protect chickens against MD, it still remains a serious threat due to increasingly frequent outbreaks of higher virulent strains of MDV combined with the incomplete immunity that is elicited by vaccination alone.MD vaccines as a class have been effectively protective against MD and provided greater than 90% protection in commercial settings. While sporadic outbreaks of MD have often been attributed to the continuous emergence of new MDV strains with increased virulence, other factors affecting vaccine efficacy have also been evaluated. Host genetics also plays a role in vaccine efficacy. Several studies were conducted to examine the influence of major histocompatibility complex (MHC) haplotype on the relative protection of MD vaccines in the early 1990s. Using experimental 15.B-congenic lines of chickens, studies found that chickens with B*15 haplotype developed better protection against MD than those with B*2 or B*13 haplotypes after receiving vaccine of either serotype 1, 2, or 3. In addition, chickens with B*5 or B*21 developed variable protection after vaccination with different MD vaccines of serotypes 1, 2, and 3. With additional studies, it was recommended to use serotype 1 vaccines in vaccination of chickens that are B*2, B*13, B*15, or B*21 haplotype, and to use serotype 2 vaccines for B*5 chickens. It was further concluded that the B-haplotype influence on vaccinal immunity against MD is significant in both experimental strains and commercial lines of chickens, and that MD vaccines should be selectively used based on the predominant B-haplotype(s) of chicken flocks to maximize vaccine protection against MD. A few studies were reported examining the influence of B-haplotype on the relative efficacy of MD vaccines in the early 1990s. Different chicken B haplotype developed different protection against MD after receiving vaccine of either serotype 1, 2 or 3. It concluded that theβ-haplotype influence on vaccinal immunity against MD is significant in both experimental strains and commercial lines of chickens. No report was found that addresses non-MHC genomic variation influence on MDV vaccination. Using specific pathogen-free chickens from a series of nineteen recombinant congenic strains (RCS) and their two progenitor lines (lines 63 and 72) of White Leghorns, which all share the same B*2 major histocompatibility complex (MHC) haplotype and the genome of each RCS comprises 7/8 the resistant background line (63) and a 1/8 random sample of the susceptible donor progenitor line (72) genome, vaccine challenge experiments were conducted to examine the effect of host genetic variation on vaccine efficacy. This study was designed to assess the role of host genetic variation contributed by the non-MHC portion of the genome on MD vaccine efficacy. Chickens from each of the lines were divided into two groups. One was vaccinated with turkey herpesvirus (HVT) strain FC126 at the day of hatch and the other was treated as a non-vaccinated control. The chickens of both groups were inoculated with a w+ strain of Marek's disease virus (MDV) on the 5th day post hatch. Statistical analysis of the Marek's disease data with a two-factor (vaccine treatment and genetic line of chickens) nominal logistic factorial model showed that the genetic line was a significant contributor to the numbers of chickens developing gross tumors or dying following MDV infection (P<0.01). The statistics of survival analyses of the MDV-infected chickens supports the conclusion that the genetic line plays a significant role in determining the MD or non-MD status and the duration of survival post MDV infection (P<0.01). Protective indices against MD of the chicken lines varied greatly with a range of 0 up to 83.3 percent.Secondly, using specific pathogen-free chickens from two resistant (63) and susceptible (72) chicken lines, which share the same MHC B*2 haplotype compared the efficacy of different three vaccines (rMd5AMeq, CVI988/Rispens and HVT) to MD. Two replicate trials were conducted for each vaccine groups. Vaccinated with rMd5 AMeq, CVI988/Rispens and HVT, respectively at day one after hatch. All trials birds of the vaccinated and unvaccinated groups were challenged with w+648A-pl0 MDV on day 5 post hatch. Chickens that died during the experiments or were killed at the termination at the end of experiments were examined for gross MD lesions, which include enlarged peripheral nerves and visceral lymphomas. Histological analysis was performed on tissues with non-definitive gross lesions. The results indicate that rMd5AMeq vaccine gave higher protection against a highly strain of MDV in both lines in comparison to CVI988/Rispens and HVT. Using specific pathogen-free chickens from a series of nineteen recombinant congenic strains (RCS), vaccine challenge experiments were conducted to compare relative efficacy of three MD vaccines in a series of 19 recombinant congenic strains of White Leghorn chickens. The results showed that the MD incidence in rMd5AMeq vaccinated birds is significantly lower than birds vaccinated with either CVI988 or HVT (P<0.01). Among the 19 RCS, nominal logistic models suggested that the total MD within different vaccine groups, and statistically very significant different between each of trial and vaccine treatment groups (P<0.001). Both the Wilcoxon test and the Log-rank test suggested the survival trends among the line by vaccine treatment groups were statistically significantly different (P<0.001). Aslo, it is clear that different genetic background of each chicken line effects on MD vaccine efficacy. All the data together suggested that non-MHC host genetic variation effect vaccine efficacy on MD. This finding could profoundly advance the understanding of disease control using vaccination, and inspire new implications to optimize the efficiency of vaccine usage.