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Abstracto

Evaluation of the Immunogenicity of a Mutagenized Rift Valley Fever MP-12 and a Recombinant Rift Valley Fever arMP12ΔNsm21/384 Vaccine Candidates in Indigenous Species of Cattle, Sheep, and Goats in Tanzania

Salekwa LP, Nyundo SB, Adamson EK, Matiko MK, Bettinger GE, Rowland JM, Palermo PM, Wambura PN, Morrill JC, Watts DM*

Objective: Rift valley fever virus (RVFV) is the cause of devastating outbreaks among domestic ruminants and humans in most African countries and in the Arabian Peninsula. Current efforts to develop and evaluate an improved veterinary vaccine to prevent RVF disease among domestic ruminants includes a live attenuated RVFV MP-12 candidate and a recombinant vaccine referred to as arMP12ΔNsm21/384 that was derived from the RVF MP-12 vaccine candidate. The aim of this study was to evaluate these RVFV vaccine candidates in domestic ruminants in Tanzania.

Methods: Six to nine months old goats (Capra aegagrus hircus), calves (Bos taurus indicus) and sheep (Ovis aries) were vaccinated subcutaneously with one ml each of 1 × 105 plaque forming units (PFU)/ml of the RVF MP-12 and/or the arMP-12ΔNSm21/384 candidate vaccines. The controls included six animals, two of each species which received 1 ml of Eagle's Minimum Essential Medium as a placebo. Blood samples were collected on day 2 before vaccination, and on the day (0) immediately before vaccination were tested for RVFV antibody to insure that only antibody negative animals were used in the vaccine trials. Samples collected on days, 3, 4, 5, 7 post-vaccination (PV) to determine the possibility of a vaccine induced viremia, and on days 4, 5, 7, 14, 21, 28, 35, 42 and 67 to determine the immune response of the vaccinated animals. Sera samples were tested for RVFV RNA by RT-PCR and for infectious virus in Vero E6 cells. The immune response was determined by testing sera samples for antibody using a commercial IDVERT ELISA kit (Montpellier-France) as well as a plaque reduction neutralization test (PRNT). Animals were observed daily for adverse effects and rectal temperature was recorded at the time of blood collection.

Results: All vaccinated animals developed RVFV neutralizing antibodies with titers ranging from 1:10 in some animals as early as day 4 and 5 PV to as high as 1:160-1:2560 over the 67 day study period with no adverse effect observed in any of the animals. The antibody titers of goats to both MP-12 and arMP-12ΔNSm21/384 vaccines was significantly higher than the response observed for sheep and cattle. A viremia was not detected in any of the vaccinated and control animals.

Conclusions: The findings of this study demonstrated that the RVFV MP-12 and arMP12ΔNsm21/384 vaccine candidates administered by the SC route elicited RVFV neutralizing antibodies in indigenous species of cattle, sheep, and goats in Tanzania, and therefore warrants further studies to assess the safety and protective efficacy of these vaccine candidates in domestic ruminants.

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