Optimizing protocols for the 919 strain-based bovine ephemeral fever virus vaccine (Ultravac®, Zoetis™): Evaluation of dose-dependent effectiveness and long-term immunity

Bovine Ephemeral Fever (BEF) is an arthropod-borne virus (arbovirus) that presents a significant challenge to the cattle industry due to its economic impact, primarily through the loss of milk production in dairy cows. Vaccination is the predominant strategy for managing the disease. We recently showed a vaccine effectiveness (VE) of 60 % of a vaccine based on the Australian 919 BEFV isolate, with a natural challenge occurring shortly after the administration of the second dose of the vaccine. Still, there is a lack of data regarding the duration of protective immunity after vaccination and its potential enhancement after the administration of three and four vaccine doses. To answer these questions we conducted a retrospective cohort study of 850 cows (7 herds), analyzing the influence of different vaccination regimens on VE and a serosurvey of 71 cows to test the longevity of BEFV-specific serum-neutralizing antibodies (SNAb). We adopted a quantitative methodology for BEF diagnosis with the use of commercially validated precision dairy monitoring technologies for milk reduction identification. Survival analysis was used to analyze the vaccine dose effectiveness. A Cox regression mixed-effect model (COXME) was fitted to the data. The analysis demonstrated the following VE compared to zero vaccine doses: 82 % (p-value<0.001) for four doses, 66 % (p-value<0.026) for three doses and 39 % (p-value = 0.3) for two doses. Corroborating with the VE results, the four-dose regimen exhibited the highest geometric mean titer (GMT) value (4.45, CI_95% = 3.99, 4.91), followed by the three-dose regimen (3.53, CI_95% = 3.08,3.98), and the two-dose regimen (2.17, CI_95% = 1.77,2.57). In light of these findings, we recommend vaccinating calves as early as four to six months old with two doses spaced one month apart, followed by a third and even fourth dose administered between six to 12 months later, ideally close to the onset of the high-risk season.