Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain.

Abstract:

: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 wild-type 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.

journal_name

Vaccine

journal_title

Vaccine

authors

Ly HJ,Nishiyama S,Lokugamage N,Smith JK,Zhang L,Perez D,Juelich TL,Freiberg AN,Ikegami T

doi

10.1016/j.vaccine.2017.10.036

subject

Has Abstract

pub_date

2017-12-04 00:00:00

pages

6634-6642

issue

48 Pt B

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(17)31444-5

journal_volume

35

pub_type

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