The goal of this project is to develop molecular methods for consistency monitoring of live viral vaccines. In our previous studies we have shown that stocks of Urabe AM9 strain used for production of Mumps vaccine live differed in two companies (SKB and Chiron SpA). The product of one company was withdrawn from the market, while the other did not show any signs of increased adverse reactions. During this year we have continued to work with Jeryl Lynn strain, and have sequences its derivatives that were de-attenuated by passaging in cell cultures. We h ave also determined sequences of a wild-type strain and its partially attenuated derivative, and identified several mutations that presumably lead to the change in virulence. We have also initiated a project on evaluaiton of yet another viaccine strain (L3) that has a history of genetic instability. We are now sequencing its genome in attempts to identify markers suitable for consistency monitoriong of vaccine production. Another branch of the project involves development of consistency monitoring approaches for Yellow Fever Vaccine. Previously we have idenitified one mutation, which occurs during virus passaging in chicken embryos. Currently we are working on creation of more sensitive methodsof mutational screening based on micro array hybridization.
