This project was an attempt to develop a surrogate test in interferon-treated neuronal cell cultures predictive of the WHO monkey neurovirulence test for type-3 OPV. The study was based on the observation that yields of type-3 OPV propagated in differentiated SY5Y human neural cells were more inhibited by treatment of the cells with gamma interferon than were yields of a virulent vaccine revertant or wild-type virus. In repeated experiments, those differences, although variable in magnitude, were consistently observed and statistically significant. In FY 1998, the increased susceptibility of gamma-interferon treated human neuroblastoma cells to fully attenuated type-3 OPV compared to revertant neurovirulent vaccine and wild-type polioviruses was confirmed. The findings were presented in poster form at an international meetings, and a manuscript is in preparation. The assays are exceptionally time-consuming, and their predictive power for various production lots of type-3 OPV and for the two other types of OPV remains undetermined. Given that two other WHO-supported tests intended to replace monkey testing of OPV are better developed, and considering that global eradication of poliomyelitis is expected within three years and that use of OPV in the USA is declining rapidly, we have decided to discontinue this project. Except for completing the a manuscript for publication and preparing a statistical decision model as an illustrative example of method development, the research will not be continued in FY 1999.
