Laboratory tests for live attenuated poliovirus vaccines.

A new generation of tests to control live attenuated poliovirus vaccines are under development based on major advances in our understanding of the molecular basis of attenuation and reversion to virulence of polioviruses. These include an alternative in vivo neurovirulence test in transgenic mice that express the human poliovirus receptor and a new in vitro test, the MAPREC (mutant analysis by polymerose chain reaction and restriction enzyme cleavage assay, that assesses consistency of production at a molecular level. Excellent progress is being made with both methods but neither is sufficiently developed yet for regulatory use. Critical review of existing control tests shows that the WHO neurovirulence test is well standardized and contributes significantly to the assessment of each batch. On the other hand, the current rct40 test is neither standardized nor particularly informative, though improvements could be made in both areas. The continued relevance of other marker tests such as the d or antigenic marker is doubtful. Potency, identity and thermal stability tests are crucial for control of the final trivalent vaccine.