**1. Introduction**

One of the greatest threats to large-fledged poultry production besides avian influenza (AI) and infectious bronchitis (IB) is Marek's disease (MD). All these disease entities cause significant economic losses through reduced weight of birds, worse feed conversion and an increased number of dead birds. Marek's disease is a viral lymphoproliferative disease in chickens that was first described in 1907 by a Hungarian researcher - Dr. Joseph Marek [1]. Then, a year later, other researchers, ie Ellerman and Bang, described similar symptoms in hens, marked with nervous symptoms, and found lymphoid tumors in internal organs that were leukemic in nature. At that time, Marek's disease was also associated with various names such as: neuritis, paralysis, and neurophomatosis gallinarum [2, 3].

It should be noted that since the initial description of this disease entity, there have been many discrepancies as to its name with regards to the visible clinical symptoms and anatomopathological changes observed in the internal organs of infected chickens.

Authors such as Biggs and Campbell have suggested keeping the name Marek's disease, instead of using avian leukemia. The disease is closely related to the presence of nervous symptoms and peripheral nerves lesions in birds [4, 5]. In the following years, Marek's disease was undoubtedly the greatest epizootic threat to birds. Within a few years, the percentage of dead birds increased significantly, usually from 10–30%, but, for example, in the case of secondary infections, even up to 60% - 80% [2]. Such a situation contributed to the undertaking of numerous scientific studies, the main aim of which was to characterize the etiological agent, to understand the mechanisms of immunity conducting after natural infection, the routes of infection, and the mechanisms of the lesions including visceral tumors and formation in internal organs and the broadly understood mechanisms of pathogenesis.

After finding that the etiological factor of Marek's disease is a virus from the Herpesviridae family, called Marek's disease virus (MDV), it was hypothesized that Marek's disease virus strains isolated from field cases may differ in their pathogenicity despite a similar clinical signs [6]. In the course of laboratory studies, it was found that the genetic material of MDV is closely related to the genetic material of the host (target-associated). The cell-free form of the virus is only found in feather follicles. This fact turned out to be useful in research on the pathogenesis of Marek's disease, mainly in terms of the mechanisms of virus spreading among birds and between buildings on the farm, but also in developing the principles of proper immunoprophylactic vaccinations. In addition, it was also helpful in determining the influence and role of antibodies raised in birds after both vaccination and natural infection [7].

The first vaccine used in the immunoprophylactic vaccinations of Mareka's disease was a vaccine based on a strain of turkey herpes virus (HVT FC126) belonging to serotype 3. It was in the form of a lyophilisate. Then came a vaccine based on the serotype 1 strain Rispens CVI 988, which required liquid nitrogen temperature for storage [8, 9]. The first studies with these vaccines were carried out to determine the efficacy of the vaccine in birds lacking maternal antibodies and in birds with maternal antibodies against Marek's disease. The vaccine used was based on the HVT (FC 126) strain in both cell-bound and cell-free form. The results of the research showed a much lower effectiveness of the vaccine based on the HVT (FC126) strain in the cell-free form. Additionally, different vaccination efficacy was found for 2 persons simultaneously vaccinating. Thus, the influence of the human factor on the process of preparation and vaccination technique on the effectiveness of the vaccination against Marek's disease was proved [10]. In subsequent studies, it was shown that there is a large variation in the incidence of Marek's disease in poultry houses located within one farm, but even in individual sectors of a given poultry houses. It has also been shown that this state of affairs can be greatly influenced by the presence of predisposing factors in the birds and on the farm in the first 8 weeks of bird life, as well as strains with different pathogenicity [11].

In 1984, Witter et al. Began research on the possibility of using a vaccine containing a strain of serotype 1, serotype 2 and serotype 3 in birds. Unfortunately, the results of these studies turned out to be unsatisfactory and the reason for this was the fact that each was the immune response of the birds. They also observed that the

#### *Marek's Disease Is a Threat for Large Scale Poultry Production DOI: http://dx.doi.org/10.5772/intechopen.98939*

incidence of the occurrence of lymphatic leukemia was significantly more frequent in vaccinated/protected birds [12, 13]. Subsequent studies have shown that Marek's disease can be divided into four successive phases: early cytolytic infection, mainly B lymphocytes, latent phase/ infection, late cytolytic infection and the phenomenon of immunosuppression, and tumor transformation of T lymphocytes [14].

Marek's disease virus strains with high pathogenicity, described as vv + (very virulent plus) strains, were found already in the early 1990s. Even then, these strains were responsible for a very high mortality among birds, even those vaccinated against Marek's disease. These studies were based mainly on classical methods in the form of a biological assay, but also molecular biology methods, mainly reaction of amplification (PCR) have already started to be used [15, 16]. In 1985, Venugopal et al. identified several genes of Marek's disease virus associated with oncogenicity/neoplastic transformation, and additionally the gen meq. They found the sequence of the latter gene only in strains classified within serotype 1. Currently, as seen, the meq gene sequence is perhaps the most frequently used sequence for the diagnosis of Marek's disease and for differentiating Marek's disease virus virulent field strains from vaccine strains [17]. A breakthrough in the research on Marek's disease was the introduction of large-scale methods of molecular biology, partial genome sequencing and then whole genome sequencing. It was mentioned that the exact sequence of individual genes and, indirectly, the mechanisms of the pathogenicity of Marek's disease virus strains and the mechanisms of the emerging immunity, both after natural infection and after vaccination, began to be studied. Efforts were also made to elucidate the full mechanism of immunosuppression caused by Marek's disease virus [18, 19]. It should also be added that the introduction of Real-Time PCR made it possible to accurately determine the viral load in 1 dose of the vaccine, which was an undoubted breakthrough in research on the effectiveness of the vaccines used [20, 21].

Our own (unpublished data) and other authors' observations confirm the fact that previously and currently used vaccines are not able to fully protect birds not only against infection, but mostly against clinical symptoms and pathological changes in internal organs of infected birds. In addition, changes in internal organs and the skin form in broiler chickens may cause confiscation on the slaughter belt up to 90% of carcasses. This is undoubtedly influenced by the progressive evolution in the pathogenicity of virus strains and the significant intensification of the scale of poultry production. That is why it seems so important to intensify research on Marek's disease [22].

It has been shown that the aforementioned meq gene can be a specific milestone by the cloning reaction of its sequence into the genome of the turkey herpes virus or the genome of the avipox virus.

A further step may be research on the sequence of the virus genome, the so-called fragmentation of non-coding RNAs in tumor cells (e.g. RNA telomerase). It is hoped that all these studies will lead to a more effective vaccine against Marek's disease [23, 24].
