Assessment of the Immunogenicity of a Novel Live Recombinant Rift Valley Fever arMP- 12ΔNSm21/384 Vaccine Candidate Following Intranasal Vaccination of Goats, Sheep and Calves in Tanzania
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Date
2020-10
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Abstract
Background: Rift Valley fever virus (RVFV) is an arbovirus that causes morbidity and mortality in livestock and
humans throughout Africa and in the Arabian Peninsula. Vaccines are effective for the prevention of Rift Valley
fever (RVF) disease, but new and improved vaccines are needed to improve the safety of available vaccines. Also, non-
invasive needle free vaccine delivery routes should be evaluated as an alternative for invasive routes of vaccination.
Objective: The aim of this proof of concept study was to evaluate the safety and immunogenicity of a novel live
attenuated recombinant RVFV arMP-12ΔNSm21/384 vaccine candidate following intranasal vaccination of goats,
calves, and sheep in Tanzania.
Methods: Healthy, 6-9 months old breeds of African sheep (Ovis aeris), goats (Capra aegagrus) and zebu calves (Bos
taurus indicus) were used in this study. The animals were purchased from local livestock keepers in the Mvomero
district of Morogoro region, Tanzania. Animals were seronegative to both RVFV and antibody at the time of use in
the vaccine trials. Animals in the test group included 10 goats, 7 sheep and 10 calves that were vaccinated in the left
nares with 50 μl each and 2 sheep were vaccinated with 100 μl each (50 μl each in the left and right nares) of a dose
that contained 4 × 10 5 PFU/50 ul of arMP-12ΔNSm21/384 vaccine, while the control group, including 2 goats, 3
sheep and 2 calves that were injected in the left nares with 50 μl of phosphate buffered saline to serve as placebo
controls. Rectal temperature was measured and blood samples were collected on day 14 and 0 before vaccination,
and on days 3, 5, 7, 14, 21, 28 and 35 post vaccinations (PV). Serum samples collected on days 14 and 0 before
vaccination were tested for RVFV neutralizing antibody by a plaque reduction neutralization test, and on days 3
and 5 PV, serum samples were tested for virus as possible evidence of a viremia in cell culture and weekly collected
samples thereafter were tested for RVFV neutralizing antibody.
Results: All animals were negative for RVFV neutralizing antibody at 14 and 0 days before vaccination and none
of the animals had detectable viremia on days 3 and 5 PV, and none had clinical manifestations throughout the
study. Among the 7 sheep, 10 goats, and 10 calves that received 50 μl each of the vaccine dose, 70% had the first
detectable antibody on either day 5, 7 or 14 PV with titers ranging from 1:10 to 1:40. The 2 sheep that received
the 100 μl each of the virus dose had the first detectable antibody on day 5 PV with a titer of 1:160. Subsequently,
animals vaccinated with the 50 μl dose had antibody titers ranged from 1:10 to 640 on days 21, 28 and 35 PV, while
those vaccinated with 100 μl maintained an antibody titer of 1:160 throughout the study. Moreover, there was no
difference in the antibody titers between animal species p=0.34, although mean antibody titers of goats were highest.
Conclusion: As a proof of concept studies, the findings demonstrated that intranasal vaccination is a promising
route for vaccinating domestic ruminants with the RVFV arMP-12ΔNSm21/384 vaccine candidate. However, these
preliminary results suggested that a larger dose of 4 × 10 5 PFU/100 ul of arMP-12ΔNSm21/384 vaccine needed to
be administered to each animal to consistently elicit a robust immune response. Also, further studies are warranted
using a larger number of domestic ruminants to confirm the immune response elicited by the larger dose of the
vaccine administered via the intranasal route.
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Keywords
Rift valley fever (RVF), RVF virus, RVF arMP-12ΔNSm21/384 vaccine, RVF antibody, Intranasal vaccination, Goat, Sheep, Calves, Tanzania