Influence of Marek's disease virus vaccines on chicken melanoma differentiation-associated gene 5-dependent-type I interferon signal transduction pathway with a highlight on their secondary impact on the immune responses post Newcastle disease virus vaccination.

Marek's disease virus (MDV) leads to a lytic infection of B-lymphocytes in chickens, and also latently infects T-lymphocytes. Although Marek's disease vaccines have been widely in use, little is known about the innate immune response of this important livestock vaccine. In this study, we tested the effect of different commercially applied Marek's disease vaccines on the expression pattern of selected genes related to chicken interferon-alpha (chIFN-α) (melanoma differentiation associated gene 5 "MDA5″ dependent) signal transduction pathway. Both MDV serotype I (Rispens) and serotype III (Herpesvirus of turkey "HVT") vaccines could stimulate MDA5 dependent-type I interferon response as early as three days post vaccination in a dose-dependent manner. The stimulation continued up to 10 days in the instance of HVT vaccine and declined in the case of Rispens. Surprisingly, increasing the doses of the two vaccines led to dose-dependent down-regulation in the expression pattern of the investigated pathway, five and ten days post vaccination. Additionally, to shed the light on the consequent effect on the immune responses of the other viral vaccine, another experimental model based on Newcastle disease virus (NDV) vaccines was designed using HVT, HVT-VP2 and Rispens MDV vaccines. The three MDV vaccines were found to reduce chicken humoral immune response post NDV vaccination. However, only Rispens and HVT-VP2 had suppressive effects on the expression of MDA5-dependent-chIFN-α related cytokines. Consistent with this finding, the protection rate and NDV- humoral immune response post challenge with virulent NDV strain was lower in case of Rispens and HVT-VP2 vaccines.

Host genetic resistance to Marek's disease sustains protective efficacy of herpesvirus of turkey in both experimental and commercial lines of chickens.

Marek's disease (MD) remains a continual threat to the poultry industry worldwide as the MD virus continues evolving in virulence. MD has been controlled primarily by intensive use of vaccines since 1969. Based on the antigenic and pathogenic differences of the viruses that the vaccines were derived from, commercially available MD vaccines are classified into three categories, MDV-1, -2, and -3 vaccines. This study was designed to compare the protective efficacy of MDV-1 (CVI988/Rispens) and MDV-3 (HVT) vaccines against challenge of a very virulent plus strain of Marek's disease virus (vv+MDV) in experimental and commercial egg-layer lines of chickens under controlled experimental conditions. The two experimental lines (63 and 72) of chickens carry a uniform MHC B*2 haplotype and are known to differ in resistance to MD. One of the two commercial egg-layer lines (WL and BL) segregates for three MHC haplotypes (B*2, B*15, and B*21); the other is unclear. MD incidences of the unvaccinated groups of both experimental lines and both commercial lines were 100% or close to 100% induced by the vv+MDV, 648A. Survived day patterns of the unvaccinated groups significantly differed between the two experimental lines, but did not between the two commercial lines, which suggested the two experimental lines do differ in resistance to MD but not between the two commercial lines. At manufacturers' recommended vaccine dosage, two HVTs conveyed comparable protection for the MD resistant line 63 chickens as did both CVI988/Rispens used in this study. The two HVTs also conveyed comparable protection for both commercial lines of chickens as did one of two CVI988/Rispens (CVI988/Rispens-A). At a 2000PFU uniform dose, HVT and CVI988/Rispens again conveyed comparable protection for the MD resistant experimental line of chickens. The findings suggest vaccine protective efficacy is modulated by factors including the types and the sources of vaccines and the genetic backgrounds of chickens. The findings also suggest HVT delivers equal protection in MD resistant lines of chickens as does the industry-recognized golden standard of MD vaccine, CVI988/Rispens.

Efficacy and safety of cell associated vaccines against Marek's disease virus grown in a continuous cell line from chickens.

The Marek's disease virus (MDV) vaccine strains CVI 988 and herpes virus of turkeys (HVT) strain FC126, usually are grown in primary chicken embryo fibroblasts (CEF). We found that the strains could be grown also in the so-called JBJ-1 cell line to titres in the same range as when chicken embryo fibroblasts were used. The JBJ-1 cell line is a fibroblast-like continuous chicken cell line, which can be grown in flat bottom tissue culture flasks, roller bottles and on micro carriers. We investigated the efficacy of experimental CVI 988 vaccines grown in JBJ-1 cells and the efficacy of combinations of CVI 988 grown in JBJ-1 cells with HVT FC 126 also grown in JBJ-1 cells. The study was performed in accordance with European Pharmacopoeia monograph 0589 for live MDV disease vaccines. Groups of 1-day-old SPF chicks were vaccinated subcutaneously or intramuscularly, with 10(2.5) TCID50 per dose of CVI 988 alone or in combination with 500PFU per dose of HVT. As a control a group vaccinated with CVI 988 grown in CEF was included. One group was not vaccinated. Five days after vaccination all chickens were challenged with the very virulent MDV strain RB1B. After challenge the chickens were observed for a period of 70 days for signs of Marek's disease (MD). The protection induced by CVI 988 grown in JBJ-1 cells and the combination of CVI 988 and HVT-FC126 both grown in JBJ-1 cells, amply complied with the requirements of the European Pharmacopoeia which prescribes that the protection index should be at least 80%. The safety of the vaccines grown in JBJ-1 cells was tested in a field study in commercial layer chickens. No signs of MD were noticed during the study and no other signs attributable to the vaccine. It is concluded that the JBJ-1 cell line is a suitable substrate for the current vaccines against MD.

Marek's disease virus: lytic replication, oncogenesis and control.

Marek's disease (MD) is caused by a ubiquitous, lymphotropic alphaherpesvirus, MD virus (MDV). MD has been a major concern in the poultry industry owing to the emergence of increasingly virulent strains over the last few decades that were isolated in the face of comprehensive vaccination. The disease is characterized by a variety of clinical signs; among them are neurological symptoms, chronic wasting and, most notably, the development of multiple lymphomas that manifest as solid tumors in the viscera and musculature. Much work has been devoted to study MD-induced oncogenesis and the genes involved in this process. Among the many genes encoded by MDV, a number have been shown recently to affect the development of tumors in chickens, one protein directly causing transformation of cells (Meq) and another being involved in maintaining transformed cells (vTR). Other MDV gene products modulate and are involved in early lytic in vivo replication, thereby increasing the chance of transformation occurring. In this review, we will summarize specific genes encoded by MDV that are involved in the initiation and/or maintenance of transformation and will focus mostly on current vaccination and control strategies against MD, particularly how modern molecular biological methods may be used to improve strategies to combat the disease in the future.

Study of host-pathogen interactions to identify sustainable vaccine strategies to Marek's disease.

Marek's disease virus is a highly cell-associated, lymphotropic alpha-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been contained by vaccination with attenuated viruses and provides the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of CD4+ T cells in susceptible chickens. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. The remarkable ability of MDV to escape immune responses by interacting with, and down-regulating, some key aspects of the immune system will be discussed in the context of genetic resistance. Resistance conferred by vaccination and the implications of targeting replicative stages of the virus will also be examined.

Immunosuppressive effects of Marek's disease virus (MDV) and herpesvirus of turkeys (HVT) in broiler chickens and the protective effect of HVT vaccination against MDV challenge.

Much of the impact of Marek's disease in broiler chickens is considered to be due to immunosuppression induced by Marek's disease virus (MDV). The present study evaluates the effects of an Australian isolate of pathogenic MDV (strain MPF 57) and a non-pathogenic vaccinal strain of herpesvirus of turkeys (HVT) (strain FC 126) on the immune system of commercial broiler chickens for 35 days following challenge at days 0 or 3 of age. It also investigates the extent of protection provided by HVT vaccine against MDV-induced immunosuppression. Immune system variables, including relative lymphoid organ weight, blood lymphocyte phenotype (CD45+/CD3+, putatively T, and CD45+/LC+, putatively B) and antibody production following vaccination against infectious bronchitis (IB) at hatch, were used to assess the immune status of chickens. Immunosuppression was also assessed by susceptibility to secondary challenge with pathogenic Escherichia coli on day 29 post-MDV challenge. MDV infection reduced the weight of the thymus and bursa of Fabricius, the numbers of circulating T lymphocytes and B lymphocytes, and IB antibody titre. The timing of these effects varied. MDV infection greatly increased susceptibility to E. coli infection. HVT alone caused mild depletion of T and B lymphocytes but no effect on immune organ weight or IB titre. Vaccination with HVT provided good protection against most of the immunosuppressive effects of MDV but not against MDV-induced growth impairment and reduced responsiveness to IB vaccination, suggesting that recent Australian strains of MDV may be evolving in virulence to overcome the protective effects of HVT.