IDENTITY OF ATTENUATING LESIONS IN LIVE COLD-ADAPTED INFLUENZA VACCINE

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My research emphasis has been on the molecular mechanisms responsible for the attenuation and the phenotypes of cold adaptation and temperature sensitivity attributed to the live, cold adapted (ca) influenza A/AA/6/60 vaccine. I have cloned all eight genes of the wild type (wt) progenitor virus and all eight genes of caA/AA/6/60 virus into the pATX vector and have then sequenced three to five clones of each gene. In addition, I am sequencing all available virulent passages of the wt A/AA/6/60 virus to determine which differences from the ca virus are common to the virulent wt's. The next step will be site mutagenesis of specific nucleotides in the ca genes identified as potentially important to virulence and reinsertion of the mutated gene into a virulent wt A/AA/6/60 to determine the effects on virulence of those mutations.