In FY 98 LMD continued to lead the WHO Collaborative Study of TgPVR mice and to coordinate results and analyses by participating consultants from CBER, NIBSC, and Canadian regulatory authorities. A WHO Consultation entitled A Regulatory Model in Transgenic Mice (TgPVR 21) for Neurovirulence Tests of Oral Poliovirus Vaccine, convened by WHO Global Programme for Vaccines and Immunization and hosted by LMD at CBER, met in June 98 to prepare documentation for consideration by the WHO Expert Committee on Biological Standardization in Oct 98.LMD developed several statistical models suitable for regulatory acceptance-rejection decisions concerning type-3 poliovirus vaccine lots. One of the statistical models, based on a comparison of odds ratios for paralysis in mice inoculated with selected doses of reference vaccine and test vaccines was selected and used to analyze existing data. That decision model was validated in Phase 3 of the WHO Collaborative Study. In nine tests performed by four laboratories, marginal vaccines were discriminated from the WHO/III reference vaccine. Three commercial RSO-derived vaccine lots (acceptable by MNVT) made in different cell substrates passed the mouse test in all laboratories. The WHO Consultation prepared report on development of the regulatory model for neurovirulence testing type-3 OPV and will be presented to ECBS in Oct 98. Additional lots of RSO-derived type-3 OPV are under study as Phase 4 ( final phase) of the WHO Study. Additional experiments in transgenic mice were performed with type-1 and type-2 OPV preparations. Appropriate infectivity doses of vaccine to be tested are under consideration. The same statistical model developed for type-3 OPV will be modified for analysis of results obtained. Representatives from three new laboratories were trained in the technique of intraspinal inoculation of mice required to conduct the Tg-mouse neurovirulence test. If their results with preliminary studies are satisfactory, they may be accepted by WHO as additional participants in the Collaborative Study.
