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United States Department of Agriculture

Agricultural Research Service

Related Topics

Research Project: Genomic Strategies for Control of Herpesviruses of Poultry

Location: Endemic Poultry Viral Diseases Research Unit

Project Number: 6612-32000-065-00
Project Type: Appropriated

Start Date: Oct 11, 2011
End Date: Oct 10, 2016

Objective:
1. Discover novel Marek’s disease virus (MDV) vaccine platforms that are safe, efficacious, and cost effective by determining genetic and biological determinants of gallid herpesvirus type 2 (GaHV-2) virulence and by developing a vaccine strain of GaHV-2 that is cell free and does not require liquid nitrogen for storage and shipment. 1.1. To generate GaHV-2 recombinants containing genes encoding immunomodulators to elicit Th1 immunity. 1.2. To develop and test vaccines that mediate cell free egress. 2. Discover novel infectious laryngotracheitis virus (ILTV) vaccine platforms that are safe, efficacious, and cost effective by determining genetic and biological determinants of gallid herpesvirus type 1 (GaHV-1) virulence and by identifying mechanisms of GaHV-1 protective immunity. 2.1. To identify predictors of virulence through sequencing of ILTV genomes of attenuated and virulent isolates from the United States. 2.2. To develop and test vaccines containing deletions in genes involved in ILTV virulence but also containing host gene additions to mediated Th1 immunity.

Approach:
1. To generate GaHV-2 recombinants containing genes encoding immunomodulators to elicit Th1 immunity. Comparative genomic will be implemented to identify genes associated with virulence. These genes will be deleted and replaced with genes encoding cytokines. Candidate vaccines will be tested in animal challenging experiments. 2. To develop and test vaccines that mediate cell-free egress. Cell free GaHV-2 vaccines will be generated by tranfering the packaging sites from the genome of a cell free avian herpesviruses into the genome of vaccine strain of GaHV-2. This hybrid genome will be encapsulated into cell free virions using either a helper virus or a packaging cell line. Chimera virions will be lyophilized and used in animal challenging experiments. 3. To identify predictors of virulence through sequencing of GaHV-1 genomes of attenuated and virulent isolates from the United States. The nucleotide sequenced of both attenuated and virulent strains of GaHV-1 will be determined using second and third generation sequencing technologies. Comparative genomic will be used to determine the polymorphorisms that occur in the attenuated genomes. 4. To develop and test vaccines containing deletions in genes involved in ILTV virulence but also containing host gene additions to mediated Th1 immunity. Comparative genomic will be implemented to identify genes associated with virulence. These genes will be deleted and replaced with genes encoding cytokines and/or RNAi constructs in order to elicit Th1 type immunity. Candidate vaccines will be tested in animal challenging experiments with virulent field isolates.

Last Modified: 4/23/2014
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