Microbiology & Immunology - Theses
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ItemImmunobiology and molecular virology of fowl adenoviruses( 1990)Three fowl adenoviruses (FAVs) representing 3 serotypes were examined both in vitro and in vivo. The choice of FAVs for this study was influenced by their suitability for future development as recombinant viral vectors to deliver vaccines to commercial poultry flocks. In vivo studies of these viruses demonstrated the wide range of immunogenicity and pathogenicity to be found amongst FAVs. Pathogenicity did not correlate with serotype, however, a direct relationship was evident between pathogenicity and stimulation of a systemic antibody response. It was also shown that this systemic antibody was not required for protection against re-infection with homologous FAVs, thereby implicating local and cell mediated immunity in resistance to FAV infection. A causal relationship was demonstrated between a group of highly virulent FAVs and the poultry disease, inclusion body hepatitis. This is one of very few reports establishing a direct relationship between FAV and disease. It is envisaged that different FAV recombinant vectors might be administered as an aerosol either simultaneously or consecutively at different stages of chicken development. The feasibility of these vaccination strategies was demonstrated and concluded that simultaneous infection with different FAV serotypes does not compromise the individual immune responses to each virus. Consecutive vaccination demonstrated the importance of using serologically distinct FAV serotypes. The in vivo cross protection between serotypes 4 and 10, along with the demonstration of strong homologies between these serotypes at the genomic level supported the proposal that these 2 classical serotypes should be combined. The in vitro examination of FAV showed that the replication kinetics of non-oncogenic FAV are very similar to those of the highly oncogenic FAV, CELO virus. For each of the 3 FAVs studied, a restriction enzyme map was constructed. These physical maps of the 45-46 Kb FAV genomes were particularly useful for identifying specific regions of the genome transcribed late in infection. For one of these FAVs, a transcription map was constructed for the late phase of replication between 10 and 24 hpi. This transcription map demonstrated similarities between FAV and human adenovirus (HAV) not previously reported. These studies provide a basis upon which to conduct future research toward the development of recombinant FAV viral vectors. The immunological studies predict that such vectors would be very flexible for the delivery of foreign genes to chickens at various ages to stimulate either local or systemic immune responses as required. The restriction enzyme and transcription maps will be invaluable to research directed at manipulation of specific regions of the FAV genome and identification of essential and non-essential genes.