Genetic diversity of recombinant Rift Valley fever virus MP-12 strain infectious clones derived from Vero cells

Rift Valley fever (RVF) is a mosquito-transmitted, zoonotic viral disease endemic to Africa and the Arabian Peninsula. This disease potentially causes devastating economic damages and serious public health problems. Live-attenuated recombinant vaccines allow rational improvement of vaccine production efficiency, protective efficacy, and vaccine safety via the genetic engineering. This study showed the generation of infectious RVF virus (RVFV) from cloned cDNA using Vero cells, which are one of a few mammalian cell lines used for vaccine manufacturing. Subsequent re-amplification of virus clones in Vero cells unexpectedly increased viral subpopulations encoding unfavorable mutations, whereas viral re-amplification in human diploid MRC-5 cells could minimize the emergence of such mutants. Rescue of recombinant RVFV from Vero cells and re-amplification in MRC-5 cells will support the vaccine seed lot systems of live-attenuated recombinant RVFV vaccines for human use.