NE1016: Genetic Bases for Resistance and Immunity to Avian Diseases
Statement of Issues and Justification
STATEMENT OF THE ISSUEDisease losses represent a significant component in the overall cost of poultry production. These costs not only include the direct losses due to increased mortality and condemnations but also increased production costs caused by suboptimal food conversion, cost of vaccines and vaccination. Several pathogens, e.g., chicken infectious anemia virus (CIAV), may cause subclinical infections that interfere with protective immune responses to other pathogens. In some cases, pathogens are in a continuing arms race with vaccines and genetic resistance in becoming more pathogenic as was eloquently described by Witter (2001) for Mareks disease. In order to battle these pathogens it will be essential to increase our understanding of the genetic bases for disease resistance and immunity, which will lead to more effective prevention and treatment procedures. These new methods will increase production efficiency and lower costs.
JUSTIFICATION
World-wide consumption of poultry products has increased drastically during the last 25 years and is expected to increase over the next decade (Roenigk, 1999). Poultry consumption rose world-wide from 31.1 million metric tons in 1988-1990 to an estimated 55 million metric tons in 1998-2000, which represents a 77% increase. Equally impressive is the increase in poultry consumption during this period from 21.8 to 29.0 % as the share of poultry, pork, and beef-veal consumption. It is expected that the shift towards poultry consumption will continue (USDA, 1997 and 1998). The continuing increase in poultry production has important economic consequences for the USA. First, the USA has one of the most efficient poultry production systems in the world and is currently an exporter of poultry products. Broiler exports in 1996 were 2.07 x 106 metric tons with a value of $2,027 x 106, (Broiler Industry 60 (5):22, May, 1997) which represented a 20.8% increase over 1995. Further growth in the production of broilers is expected and it is anticipated that the USA poultry producers will profit from increased worldwide demand. In addition, the production of poultry feed is also in a large part dependent on the USA grain and soya production, providing additional benefits to the economy. Although these predictions may have been overly optimistic in view of the current economical situation, poultry production in the USA remains strong. Broiler placements in the USA totaled 7.23 billion in the first 10 months of 2002 (WATT Global e-NEWS, October 26, 2002).
The impact of diseases is one major impediment for increased productivity. Total losses caused by specific diseases not only include mortality, decreased egg production, and condemnations but also costs of vaccination, chemotherapy, and eradication programs. Although there are no recent published data available on these losses, Biggs (1982) quoted a loss of $1,427 x 106 in 1975 for the US alone. Witter and Schat (2002) estimated that the total losses (mortality, vaccination costs, reduced egg production) caused by Mareks disease (MD) were close to one billion dollars worldwide in 1984. These losses have certainly increased over the last 17 years, especially given the emergence of ever more virulent strains of MDV. These so-called vv+MDV strains are causing MD outbreaks in chickens properly vaccinated with MDV (Witter, 2001). Recent problems with Salmonella enteriditis have caused considerable economic losses and further losses can be expected. For example, if FDA suggestions for S. enteriditis elimination are implemented, the costs of table eggs will increase dramatically (Dr. D. Kradel, personal communication). The losses due to S. enteriditis in the US are based on the human health impact of only a small number of positive hens. In addition to the clearly identifiable problems, a substantial portion of the losses is caused by suboptimal production as a consequence of interactions among management, genetic resistance and disease agents (Biggs, 1982).
Reduction of these losses depends on several interrelated factors; the interaction between genetic background of the chicken and the development of the immune responsiveness is especially relevant. Immune responsiveness is at least in part determined by the major histocompatibility complex (MHC) as well as by other genetic traits. The collaborating NE-60 stations have demonstrated MHC-related resistance to a number of diseases. Information demonstrating that genetic selection related to immunity may reduce economical losses is important, because successful adaptation of appropriate selection procedures by primary breeders may lead to a rapid dissemination of more resistant strains and a subsequent reduction in losses. NE-60 has invited representatives of breeder organizations to the annual meetings to disseminate new information on an informal basis. These breeder representatives also bring information on field problems and comments on the importance of approaches taken by NE-60. These aspects will become even more important with the advent of biotechnology applications especially because the chicken genome will be sequenced during the next five years.
At this time, the sequence of the MHC related genes is already available (Kaufman et al, 1999). These data will be important toward development of tailored vaccines presenting epitopes that are recognized by specific haplotypes. ARS-ADOL station has already shown that certain genetic strains respond differently to different MD vaccines. Recent data from the NYC station have shown which specific gene products are recognized in cell-mediated immune responses. The combined data from these groups indicate that tailored vaccines may become a distinct possibility in the future and research towards this goal is included in this proposal. Similarly, several NE-60 groups are working on the regulation of immune responses by studying cytokine activation pathways that are important for innate and acquired immune response.
In the previous five-year project outline it was stated that rapid progress in the understanding of the interactions between genetic background and disease resistance was expected over the next 5 to 10 years. This prediction was based, in part, on the development of MHC-congenic strains and the development of monoclonal antibodies (Mabs) for lymphocyte (sub)populations by several participating stations of NE-60. During the last five years, we have also made strong progress in the molecular aspects of genetic resistance to diseases by cloning several cytokine genes (e.g., ARS-PBESL) and examining the expression patterns of these cytokines using quantitative real-time PCR assays (several NE-60 stations). The combination of these new and previously developed tools have led to a very productive first 4 years of the current grant with 267 papers published and additional papers in press both of which include a substantial number of joint publications among NE-60 stations (Publications list).
Further progress in improving genetic resistance to diseases will require the application of advanced techniques in immunology, biochemistry, virology, bacteriology, parasitology, molecular biology and genetics to study pathogens using well-defined strains of chickens in facilities designed to contain infectious agents. NE-60 members form the ideal team to pursue the proposed studies, because they have: i) a proven collaborative research record, and ii) as a group the needed expertise listed above.
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