Infectious bursal disease (IBD), caused by an avibirnavirus, has been an economically significant, widely distributed condition affecting immature chickens since 1960. The classical type 1 conventional strain is responsible for up to 5% mortality in susceptible flocks. As a result of immunosuppression, growth rate, liveability, and productivity may be adversely affected by subsequent exposure to a wide range of viral, bacterial, and protozoal agents. The emergence of highly pathogenic strains of IBD virus in 1988 caused heavy losses in broiler and replacement breeder and commercial egg pullets in Europe, and subsequently in Africa and Asia. The causal virus is extremely lymphocidal with an affinity for immature B cells resulting in bursal atrophy approximately four days after infection. IBD virus is resistant to environmental exposure and is transmitted laterally by direct and indirect contact between infected and susceptible flocks. Conventional IBD is controlled by immunization of parent stock followed by vaccination of progeny after maternal antibody levels have waned. Parent level stock is immunized by one or two successive doses of live, mild or intermediate strain, attenuated vaccine to prime the immune system, followed by inactivated oil emulsion vaccines at maturity and at the mid-point of the laying cycle to boost immunity and ensure transfer of protective maternal antibody to progeny. Highly pathogenic IBD is controlled by a number of alternative strategies, including administration of live vaccines of low attenuation or simultaneous doses of live intermediate strain attenuated vaccine with inactivated oil emulsion during the first week. All successful programmes require diligent care regarding handling and administration of vaccine. Serological monitoring using automated ELISA technology is an accepted method of confirming that flocks are adequately protected. In the future recombinant and subunit vaccines will be developed to control existing strains and the variants which will emerge in areas with a high density of poultry production. . (1988) Comparative studies on structural and antigenic properties of two serotypes of infectious bursal disease virus. Journal of General Virology 69: BENTON, W. J., COVER, M. S. and ROSENBERGER, J. K. (1967a) Studies on the transmission of the infectious bursal agent (IBA) of chickens. Avian Diseases 11: 430-438 BENTON, W. J., COVER, M. S., ROSENBERGER, J. K. and LAKE, R. S. (1967b) Physico-chemical properties of the infectious bursal agent (IBA) Avian Diseases 11: 438-445 BENGELSDORFF, H-J. and BERNHARDT, D. (1971) Serological examinations after vaccination of chicks with mouse-adapted infectious bursitis virus. Proceedings of the 19th World Veterinary Congress, Mexico City, Mexico 2: 786-787 BOX, P. (1988) Antibody profile of broiler breeders hens and their progeny immunized with bursalderived or embryo-origin killed infectious bursal disease vaccine.

Infectious bursal disease (IBD) emerged in 1957 as a clinical entity responsible for acute morbidity and mortality in broilers on the Delmarva peninsula. The condition spread rapidly and was recognized throughout the U.S. broiler and commercial egg production areas by 1965. Early attempts to isolate the etiologic agent were impeded by a lack of specific-pathogen-free (SPF) eggs and by deficiencies in viral and serologic techniques. By 1967, the highly infectious nature of the agent was recognized. Reliable methods were developed to isolate the virus in embryonated eggs and to adapt it to tissue culture. The agent was characterized as a virus belonging to a new taxonomic group in 1976. The immunosuppressive property of IBD virus was first recognized in 1970 and was confirmed in structured trials in 1976. An early method of control involved planned infection of chickens. This technique lowered IBD mortality but often resulted in immunosuppression and further dissemination of field virus. A live attenuated vaccine was then developed, based on mild field isolates passaged in SPF eggs. This vaccine was federally licensed as the first of its kind for interstate use in 1968. It remains widely used today in breeders as a primer and in the control of very virulent IBD in many countries. The first two decades following emergence of IBD were characterized by close cooperation among scientists in academia, the biologics industry, and the USDA. By 1976, mortality caused by IBD was effectively controlled by vaccination. However, the more subtle effects of immunosuppression and the tremendous economic impact of the disease were just starting to be appreciated. Recognition of Delaware variants in the mid-1980s and emergence of very virulent forms of the condition in Europe and Asia beginning in 1989 attest to the continuing importance of IBD.

In the present study we describe the rapid development of an attenuated live vaccine for GA08, a new serotype of infectious bronchitis virus, using a heat-treatment method. Incubation of the GA08 strain of IBV at 568C and passage in embryonated eggs was used as a method to fast track the attenuation process. The virus was incubated in a 568C water bath and aliquots were removed every 5 min for up to 1 h, and then each aliquot was inoculated into 10-day-old embryonated eggs. Virus with the longest incubation time that produced lesions in the embryos was harvested, again incubated at 568C as described and passaged in embryonated eggs. Attenuation of the virus, designated GA08/GA08HSp16/08, was verified in 1-day-old specific pathogen free chicks. A 10x dose of the vaccine was found to be safe for 2-week-old broiler chicks of commercial origin. The efficacy of the heat-treated attenuated virus was determined by vaccinating broiler chicks of commercial origin at 1 and 14 days of age intraocularly/intranasally. Vaccinated birds that were challenged with 10 4.5 median embryo infectious doses of pathogenic GA08 virus/bird at 28 days of age were protected from the disease, and challenge virus was only detected in the trachea of one of 21 birds by realtime reverse transcriptase-polymerase chain reaction at 5 days post challenge. The attenuation process took 10 weeks to complete, which is a substantially shorter time than required to attenuate infectious bronchitis virus by serial passage in embryonated eggs without heat treatment (38 weeks or more).

Congress passed the Virus-Serum-Toxin Act in 1913, giving the U.S. Department of Agriculture (USDA) authority to prevent the importation or interstate shipment of worthless, contaminated, dangerous, or harmful veterinary biological products. The passage of this act marked the beginning of regulatory requirements for veterinary biological products in the United States. In 1913, only a few biologics establishments produced products for the poultry industry. The first license issued by the USDA for a poultry product was in 1918 to the University of California, Berkeley, for fowlpox vaccine. The list of biological products for poultry grew slowly in the 1920s. However, this began to change with the licensing of laryngotracheitis vaccine in 1933; pigeonpox vaccine in 1939; several Newcastle disease vaccines (inactivated in 1946, Roakin strain in 1948, B1 strain in 1950, and La Sota strain in 1952); and the first bronchitis vaccine in 1953. With the development of these and other new products, the biologics industry began to move its emphasis on hog cholera serum and virus to one based on the production of numerous new vaccines and bacterial products. The USDA's approach to the regulation of biologics in the early 1950s was still geared to the production of hog cholera products; however, as a result of the intervention of a group of dedicated poultry scientists, who were concerned about the poor performance of Newcastle disease vaccines, this soon changed. This presentation describes the initiation and development of modern standards for poultry biologics that occurred as a result of this intervention. The development and improvement of standards and regulatory requirements to address mycoplasma, leukosis, and other extraneous virus contaminations in chicken embryo origin products are reviewed. The licensing of products to meet new and emerging disease problems in the poultry industry and the close interaction among research scientists, poultry industry, biologics manufacturers, and government regulatory officials that has been needed to ensure the availability of products that meet appropriate standards of purity, safety, potency, and efficacy are also addressed.

By the end of the 1960s, The United States Department of Agriculture (USDA) had established the basic purity and safety standards for poultry biologics in the United States and had licensed products to address many of the major poultry diseases of concern at that time. The emergence of new diseases, advances in scientific technology, and changes in poultry husbandry practices that occurred in the 1970s to the 1990s required the development of many new and amended regulatory requirements to keep abreast of the changing needs of the poultry industry. Veterinary Services often approved the use of special or conditional licensing procedures to shorten the time to license products needed to address emerging diseases. Infectious bronchitis, bursal disease, fowl cholera, duck virus enteritis, avian influenza, and other vaccines were rapidly licensed to address emerging disease problems using this procedure. Changes in labeling and packaging requirements were made to address changing vaccination practices. Veterinary Services permitted diluents to be shipped separate from product, first for Marek's disease vaccine and later for vaccines recommended for administration by automatic vaccinating machines. The maximum number of doses permitted to be in one container and package were also amended to address the increased size of poultry flocks. Veterinary Services also approved the use of split manufacturing procedures that permitted two or more licensed manufacturers to work together in the production of a product. This innovative use of licensing products for further manufacture allowed the industry to use production facilities more efficiently and provided a wider variety of combination products. In 1985, Congress passed an amendment to the Virus-Serum-Toxin Act that gave USDA the authority to regulate all veterinary biological products shipped in or from the United States. This amendment brought intrastate biologics manufacturers under federal jurisdiction and ensured all biological products shipped in or from the United States met the same standards of purity, safety, potency, and efficacy. The development of new recombinant DNA (r-DNA) techniques for the production of vaccines required USDA to establish new procedures and rules for the review of these products prior to their release into the environment and eventual licensure. Compliance with the National Environmental Policy Act required the preparation of environmental risk assessments and public participation in the field testing and licensing of live r-DNA products. This article addresses some of the history of these and other changes in regulatory requirements for poultry products that took place in the 1970s to the 1990s, but space does not permit us to address all of the changes that have occurred. We have presented some of what we consider the most notable events in this process and leave it up to future historians to address events that may not have been included.