Randomized Controlled Field Trial to Assess the Immunogenicity and Safety of Rift Valley Fever Clone 13 Vaccine in Livestock.

Background: Although livestock vaccination is effective in preventing Rift Valley fever (RVF) epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa. Methods: In a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats) in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365. Results: In vaccinated goats (N = 72), 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77), 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42) did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 – 9.2) in cattle, 90.0 (95% CI, 25.1 – 579.2) in goats, and 40.0 (95% CI, 16.5 – 110.5) in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals. Conclusions: The results suggest RVF Clone 13 vaccine is safe to use and has high (>90%) immunogenicity in sheep and goats but moderate (> 65%) immunogenicity in cattle. Author Summary: Although livestock vaccination is effective in preventing Rift Valley fever (RVF) outbreaks, there are concerns about safety and effectiveness of the only commercially available vaccine for the disease. Here, we conducted a field trial in Kenya to evaluate the safety and ability to induce protection for a new RVF vaccine, referred to as Clone 13, that was recently registered in South Africa. A total of 404 animals, consisting of cattle, sheep, and goats, were divided two groups and one group was vaccinated with Clone 13 vaccine while the other group was not vaccinated. The animals were followed for one year and analyzed for RVF antibody levels at days 14, 28, 56, 183, and 365 after vaccination. Between 91% and 97% of vaccinated sheep and goats develop antibodies to the vaccine, whereas only 67% of the vaccinated cattle developed antibodies. These finding indicate that the Clone 13 vaccine induces high levels of protective antibodies in sheep and goats and moderate levels in cattle. The vaccine was safe since none of vaccinated animals developed evidence of RVF disease including deformities in newborns, and only 1 out of 120 pregnant animals had an abortion that was not associated with the RVF disease. [ABSTRACT FROM AUTHOR]