In FY 2002 LMD continued training and consulting laboratories interested in implementation of the transgenic mouse neurovirulence test for practical use. WHO COllaborative Study on evaluation and validation of transgenic mouse neurovirulence test (NVT) was started in 1993 and completed in 2000. Mouse NVT developed at LMD/CBER was widely evaluated in five phases of the WHO Collaborative Study for all three types Oral Poliovirus Vaccine (OPV). In October 1999 WHO Expert Committee on Biological Standardization (ECBS) considered results and documentation of the collaborative study and made the decision to include the Tg mouse NVT in the WHO Requirements for type 3 OPV as alternative to the monkey test (WHO Expert Committee on Biological Standardization, WHO Technical Report Series 904. 2000, pp. 31-93). In framework of phases 4 and 5 of the WHO Collaborative Study neumerous experiments in transgenic mice were performed with type-1 and type-2 OPV preparations. Statistical pass/fail decision model developed for type-3 OPV was validated for types 1 and 2 in several laboratories in FY 2000. In June 2000 the WHO Consultation Group met again to analyse and update documentation on type 1 and 2 OPV. Documentation prepared by the group was presented to the WHO ECBS in October 2000. The ECBS analysed updated documentation and made the decision to include the Tg mouse neurovirulence test in the WHO Requirements for OPV as alternative to the monkey test for all three types OPV. The WHO assigned LMD as a center for training of and consulting with all interested parties. The implementation stage (introduction of the mouse test into manufacturing practice and by national regulatory authorities) is in progress now. Several manufacturers are going through different stages of the implementation process. Practical use of Tg mouse NVT was demonstrated recently by solving some problems one company faced with the monkey NVT. At present time Tg mouse NVT is suggested for control of neurovirulence of vaccine other than OPV, such for example as HIV recombinant vaccine candidate based on Sabin poliovirus strain as vector.
