DEVELOPMENT OF RATIONALLY DESIGNED HCMV VACCINE STRAINS

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DESCRIPTION: CMV is a major source of morbidity and mortality in immunocompromised individuals. This virus is responsible for a range of clinically apparent syndromes, ranging from sight-threatening retinitis in AIDS patients to life-threatening pneumonia in bone marrow and renal allograft transplant recipients. In the U.S. alone, over 4 billion dollars of health care costs are incurred as a consequence of congenital infection and disease. Our long term goal is to create a safe and efficacious live attenuated CMV vaccine that will confer protection from disease. Our approach for creating a live attenuated CMV strain is based on combining genes from two well characterized CMV strains. Genes from the Toledo strain of CMV, a virulent, wild-type virus, and Towne, an avirulent, cell culture adapted virus which causes no disease in adults, can be recombined to form effective live, attenuated virus vaccine candidates by cotransfecting overlapping cosmids into a permissive cell. By identifying genes in Toledo which contribute to its virulence and inserting these into the safe, avirulent Towne genome, a strain can be created which will confer an increased immunogenicity or replication to Towne. This new CMV will be tested to assess whether it protects recipients from CMV disease.