Evaluation of antigenic comparisons among BVDV isolates as it relates to humoral and cell mediated immunological measures

Authors: Falkenberg, Shollie; Dassanayake, Rohana; TERHAAR, BRETT - Frontier Scientific; RIDPATH, JULIA - Retired ARS Employee; Neill, John; ROTH, JAMES - Iowa State University

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/19/2021
Publication Date: 6/15/2021
Citation: Falkenberg, S.M., Dassanayake, R.P., Terhaar, B., Ridpath, J., Neill, J.D., Roth, J. 2021. Evaluation of antigenic comparisons among BVDV isolates as it relates to humoral and cell mediated immunological measures. Frontiers in Veterinary Science. 8. Article 685114. https://doi.org/10.3389/fvets.2021.685114.
DOI: https://doi.org/10.3389/fvets.2021.685114

Interpretive Summary: Antigenic differences between bovine viral diarrhea virus (BVDV) vaccine and field strains can lead to lack of efficacy. In general, antigenic differences among BVDV strains are evaluated using virus neutralization titers (VNT). Typically, VNT are correlated with protection and analytical methods for quantifying antigenic relationships associated with VNT are being evaluated. Data generated using these methods illustrate that the genetic characterization does not always correlate to antigenic characterization. Furthermore, antigenic comparisons using VNT only account for the antibody component of the immune response and do not include all protective immune responses to BVDV. While these novel analytical methods provide the opportunity to understand antigenic relatedness associated with antibody responses, cell mediated immunity (CMI) is not accounted for and is an important component of the immune response and conferring protection against BVDV. Currently, there is little data regarding potential antigenic differences between BVDV vaccine and field strains as measured by CMI responses. Data from the current study would suggest that not only is there an antigenic component associated with antibody responses as measured by VNT, but antigenic differences can also be observed for CMI. Further research is needed to understand the significance of antigenic differences associated with CMI and the implications as it relates to protective immune responses.

Technical Abstract: Antigenic differences between bovine viral diarrhea virus (BVDV) vaccine and field strains can lead to reduced vaccine efficacy. Historically, antigenic differences among BVDV strains were evaluated using techniques based on polyclonal and monoclonal antibody activity. Genetic comparisons are used for sorting pestiviruses into different species and subgenotypes but phylogenetic comparisons may not accurately infer antigenic relationships. The most common method for antigenic comparison among BVDV isolates is determination of virus neutralization titers (VNT). The VN titer is largely a measure of antibodies against the E2 structural protein. E2 is an immunodominant protein and induces the production of virus-neutralizing antibodies. VN titers correlate with protection and novel analytical methods for quantifying antigenic relationships associated with VN titers have been developed. Varying levels of cross-reactivity among BVDV species and subgenotypes, based on VN, have been demonstrated. Data generated using these methods illustrate that the genomic phylogeny does not always correlate to antigenic similarity. Furthermore, antigenic comparisons using VN titers only account for the humoral component of the immune response and thus gives an incomplete picture of protective immune responses to BVDV. While these novel analytical methods provide the opportunity to better quantify cross reactive relationships, these methods do not incorporate cell mediated immunity (CMI) responses which are an important component in conferring protection against BVDV. The importance of observing cross reactivity based on both humoral and CMI is illustrated by vaccination/challenge studies examining cross-protection against different field isolates. Currently, there little data regarding potential antigenic differences between BVDV vaccine and field strains as measured by CMI responses. It is thought that CMI is directed at both structural but non-structural proteins, but it is unknown if the epitopes associated with CMI are associated with differences in cross protection. The goal of the current paper is to review previous literature as it relates to antigenic differences associated with humoral immunity and highlight current data utilizing CMI responses to measure potential antigenic differences existing between BVDV vaccine and field strains. Conferring protection against BVDV as a method for control of BVDV in cattle populations is still a complex issue and requires a multifactorial approach to understand factors associated with vaccine efficacy or conversely vaccine failure.