Efficacy of a Rift Valley fever virus vaccine against an aerosol infection in rats

Abstract

The formalin-inactivated Rift Valley fever virus (RVFV) vaccine, TSI-GSD-200, was administered subcutaneously to highly susceptible adult Wistar-Furth rats (LD50-1 p.f.u., ZH501 strain). Vaccine was administered on days 0, 7 and 28, the same time course used for at-risk personnel. Six months postimmunization, when the serum plaque-reduction neutralization titre (PRNT)80 had declined to low or undetectable levels, rats were challenged with 4.4 log10 p.f.u. of the virulent ZH501 strain in a nose-only dynamic aerosol apparatus. Ninety-seven per cent (33/34) of the non-vaccinated control rats died. In contrast, only 32% (33/105) of the vaccinated animals died. In vaccinated rats that succumbed, there was a doubling of the mean time to death and the cause of death shifted from hepatitis to encephalitis. Rats with a PRNT80 of greater than or equal to 1:40 were protected from clinical disease and histological evidence of hepatic or encephalitic lesions. While the precise mechanisms of immunity against aerosol challenge remain unresolved, here the serum PRNT titre correlated with protection.