Innovative in cellulo method as an alternative to in vivo neurovirulence test for the characterization and quality control of human live Yellow Fever virus vaccines: A pilot study

The FNV strain was used here as a prototype of neuroinvasive/neurovirulent YF viruses, while 17D was used as a prototype of non-[neuroinvasive/neurovirulent] virus. We compared the capacity of FNV and 17D viruses to cross the BBB, in the BBB-Minibrain model, we assessed their ability to infect the Minibrain, multiply in it, and perturbate its homeostasis. Our results demonstrate that it is feasible to detect neurovirulent variants, reliably and timely in cellulo with the BBB-minibrain. This system represents a promising development, and could ultimately enable the replacement of animals for neurovirulence testing of vaccine from which live virions can cross the BBB.311