Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula
that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is
important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic
in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also
important for live-attenuated strains to encode unique genetic markers for the differentiation from wildtype
RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain
via the introduction of 584 silent mutations. To minimize the impact on protective effic... More
Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula
that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is
important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic
in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also
important for live-attenuated strains to encode unique genetic markers for the differentiation from wildtype
RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain
via the introduction of 584 silent mutations. To minimize the impact on protective efficacy, codon usage and
codon pair bias were not de-optimized. The resulting rMP12-GM50 strain showed 100% protective efficacy
with a single intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization test.
Moreover, outbred mice infected with one of three pathogenic reassortant ZH501 strains, which encoded
rMP12-GM50 L-, M-, or S-segments, showed 90%, 50%, or 30% survival, respectively. These results indicate
that attenuation of the rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments.
Recombinant RVFV vaccine strains encoding similar silent mutations will be also useful for the surveillance
of reassortant strains derived from vaccine strains in endemic countries