Effectiveness of two intranasal vaccines for the control of bovine respiratory disease in newborn beef calves: A randomized non-inferiority multicentre field trial

Abstract

Bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (bPI3V) are major causes of bovine respiratory disease (BRD) in newborn calves worldwide. Vaccination is widely used to prevent BRD, and intranasal vaccines for BRSV and bPI3V were developed to overcome interference from BRSV and bPI3V-specific maternally derived antibodies. Many experimental challenge trials have demonstrated that intranasal vaccines for BRSV and bPI3V are efficacious, but effectiveness under field conditions has been demonstrated less often, especially for newborn beef calves. The objective of this field trial was to compare the effectiveness of a newly available commercial BRSV-bPI3V intranasal vaccine with that of a benchmarked one in newborn beef calves reared in a cow-calf system. A total of 935 calves from 39 farms were randomized into two vaccine groups (Bovalto Respi Intranasal [Vaccine A], n=468; Rispoval RS+PI3 Intranasal [Vaccine B], n=467), and monitored during the in-house risk period up to three months after vaccination. Non-inferiority analysis was performed by calculating the difference in BRD prevalence between the two vaccine groups. No significant differences were observed between vaccines regarding clinical outcomes of morbidity, mortality, duration between vaccination and BRD occurrence, or treatments required. Because the upper limit of the 2-sided 95% confidence interval of the difference in BRD prevalence between the two treatment groups (0.8%) was less than the margin of non-inferiority (δ=5%), a non-inferiority of Vaccine A was concluded. In conclusion, Vaccine A is at least as effective as Vaccine B for the prevention of BRD in newborn beef cattle in a cow-calf system under field conditions.

Keywords: Bovine; Bovine parainfluenza-3 virus; Bovine respiratory syncytial virus; Calf; Intranasal vaccine; Vaccination.

Fig. 1

Four possible scenarios of a non-inferiority trial comparing Vaccine A to Vaccine B for preventing BRD. The margin of non-inferiority (δ) is drawn by a vertical dashed line. P_BRD is the prevalence of BRD cases diagnosed during the study risk period of housing after vaccination. Error bars indicate 2-sided 95% confidence interval (CI) of the difference in BRD incidence (Piaggio et al., 2012). S: if the CI lies wholly to the left of zero, Vaccine A is superior. NI: if the CI lies to the left of δ and includes zero, Vaccine A is non-inferior. IC: if the CI includes δ and zero, the difference is non-significant but the result regarding non-inferiority is inconclusive. I: if the CI is wholly above δ, Vaccine A is inferior. VT is the representation of the main outcome of this non-inferiority trial. The black block indicates the difference in BRD incidence between Vaccine A group and Vaccine B group. Non-inferiority of Vaccine A compared to Vaccine B at a margin of 5% is demonstrated because the 95% CI lies to the left of δ (=5%) and includes zero.