Multivariate analysis reveals that BVDV field isolates do not show a close VN-based antigenic relationship to US vaccine strains

Objective Evaluate bovine viral diarrhea virus (BVDV) antigenicity by using virus neutralization titers (VNT) analyzed using the principal component analysis (PCA) from antisera generated against US-based vaccine strains against both US-origin field isolates and non-US-origin field isolates. Results Data from both independent analyses demonstrated that several US-origin and non-US-origin BVDV field isolates appear to be antigenically divergent from the US-based vaccine strains. Results from the combined analysis provided greater insight into the antigenic diversity observed among BVDV isolates. Data from this study further support genetic assignment into BVDV subgenotypes, as well as strains within subgenotypes is not representative of antigenic relatedness. PCA highlights isolates that are antigenically divergent from members of the same species and subgenotype and conversely isolates that belong to different subgenotypes have similar antigenic characteristics when using antisera from US-based vaccine isolates

Use of multivariate analysis to evaluate antigenic relationships between US BVDV vaccine strains and non-US genetically divergent isolates

Bovine viral diarrhea virus (BVDV) comprises two species, BVDV-1 and BVDV-2. But given the genetic diversity among pestiviruses, at least 22 subgenotypes are described for BVDV-1 and 3-4 for BVDV-2. Genetic characterization is generally accomplished through complete or partial sequencing and phylogeny, but it is not a reliable method to define antigenic relationships. The traditional method for evaluating antigenic relationships between pestivirus isolates is the virus neutralization (VN) assay, but interpretation of the data to define antigenic relatedness can be difficult to discern for BVDV isolates within the same BVDV species. Data from this study utilized a multivariate analysis for visualization of VN results to analyze the antigenic relationships between US vaccine strains and field isolates from Switzerland, Italy, Brazil, and the UK. Polyclonal sera were generated against six BVDV strains currently contained in vaccine formulations, and each serum was used in VNs to measure the titers against seven vaccine strains (including the six homologous strains) and 23 BVDV field isolates. Principal component analysis (PCA) was performed using VN titers, and results were interpreted from PCA clustering within the PCA dendrogram and scatter plot. The results demonstrated clustering patterns among various isolates suggesting antigenic relatedness. As expected, the BVDV-1 and BVDV-2 isolates did not cluster together and had the greatest spatial distribution. Notably, a number of clusters representing antigenically related BVDV-1 subgroups contain isolates of different subgenotypes. The multivariate analysis may be a method to better characterize antigenic relationships among BVDV isolates that belong to the same BVDV species and do not have distinct antigenic differences. This might be an invaluable tool to ameliorate the composition of current vaccines, which might well be important for the success of any BVDV control program that includes vaccination in its scheme