Evaluation of the safety and immunogenicity of rift valley fever mp-12 and armp-12δnsm21/384 vaccine candidates in goats (capra hircus), sheep (ovis aries) and calves (bos indicus) from Tanzania
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Date
2020
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Publisher
Sokoine University of Agriculture
Abstract
Rift Valley fever virus (RVFV) is an arbovirus that causes Rift Valley fever (RVF), a
disease that causes morbidity and mortality in livestock and humans. Among the measures
considered, vaccines are the most effective control strategy against this RVF disease.
While we have available vaccines, effective vaccines and better routes of vaccination are
needed to prevent RVF among livestock and humans. Therefore, the aim of this study was
to evaluate the safety and immunogenicity of a live attenuated RVFV MP-12 and a
derivative recombinant RVFV arMP-12ΔNSm21/384 vaccine using the intramuscular (IM)
route of vaccination in Tanzanian calves, and goats. Also, a proof of concept study was
conducted to evaluate the safety and immunogenicity of the RVFV arMP-12ΔNSm21/384
vaccine using the intranasal (IN) route of vaccination in the same species, as well as sheep.
Overall, a total of 61 animals (goats, sheep and calves) aged 6 to 9 months old were used
in this study. Twenty five animals, including 5 goats and 3 calves were vaccinated IM with
a dose of 1×105 plaque forming units (PFU)/ml of RVF MP-12 and 8 goats and 5 calves
were vaccinated with the RVF arMP-12ΔNSm21/384 vaccine, and 2 goats and 2 calves
received a placebo to serve as controls. Afterward, rectal temperatures were recorded on
day 1, 2, 3, 4, 5, 7 then weekly throughout the study. Blood samples were collected on day
14 before vaccination and on the days 0, 3, 5, 7, 14, 21, 28, 35, 70, 84 and 87 post
vaccinations (PV). At day 87 PV, all IM vaccinated animals were revaccinated via the IM
route with 1×104 PFU/ml of RVF MP-12 vaccine and blood samples were again collected
on days 94, 101 and 108 PV. As a proof of concept study, 7 sheep, 10 goats and 10 calves
were vaccinated intra-nasally (IN) with 50 μl of 1×105 PFU of arMP-12ΔNSm21/384
vaccine and 2 sheep were vaccinated with 100 ul of 1x 105 PFU of the arMP-
12ΔNSm21/384 vaccine, and 7 animals (2 goats, 3 sheep and 2 calves) received a placebo
to serve as controls. Rectal temperatures were recorded and blood samples were collected
14 days before and on day, 0 immediately before vaccination and on days 3, 5, 7, 14, 21,
28 and 35 PV. Samples collected in both studies on the day -14 before vaccination, day 0
immediately before vaccination, 3 and 5 were tested for viremia by virus isolation
attempted in Vero E6 cells and samples collected on days 7, 14, 21, 28, 35, 70, 84, 87, 94,
101 and 108 PV were tested for RVFV neutralizing antibody by the plaque reduction
neutralization test (PRNT). None of the animals had detectable viremia and clinical
manifestations throughout the study. All IM vaccinated animals and 70% of each species
in the IN vaccinated animals had the first detectable antibody on either day 5 or 7 PV,
respectively and antibody titers ranged from 1: 10 to 1:40. Afterwards, antibody titers
increased and ranged from 1:10 to 1:640 for the IN and 1:40 to 1:640 for IM vaccinated
animals. The antibody response was lower for the IN vaccinated animals, but goats that
were vaccinated both by the IM and IN routes responded better than other species while
calves had the lowest antibody titers. Therefore, these findings demonstrated that the IN
route of vaccination is promising for use in place of the IM route to avoid the use of
needles that can cause needle stick injuries and the IN route may prove to be a safer and
more efficient route of vaccination especially in mass vaccination campaigns. However,
based on the preliminary results of this study, the volume of the vaccine dose for IN
vaccination may need to be increased from 50 μl to 100 ul per animal to improve the
immunogenicity of the vaccine.
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Keywords
Immunogenicity, Rift valley, Vaccine candidates, Tanzania, Goats (capra hircus), Sheep (ovis aries), Calves (bos indicus)