Impact of species and subgenotypes of bovine viral diarrhea virus on control by vaccination.

Bovine viral diarrhea viruses (BVDV) are diverse genetically and antigenically. This diversity impacts both diagnostic testing and vaccination. In North America, there are two BVDV species, 1 and 2 with 3 subgenotypes, BVDV1a, BVDV1b and BVDV2a. Initially, US vaccines contained BVDV1a cytopathic strains. With the reporting of BVDV2 severe disease in Canada and the USA there was focus on protection by BVDV1a vaccines on BVDV2 disease. There was also emphasis of controlling persistently infected (PI) cattle resulted in studies for fetal protection afforded by BVDV1a vaccines. Initially, studies indicated that some BVDV1a vaccines gave less than 100% protection against BVDV2 challenge for fetal infection. Eventually vaccines in North America added BVDV2a to modified live virus (MLV) and killed BVDV1a vaccines. Ideally, vaccines should stimulate complete immunity providing 100% protection against disease, viremias, shedding, and 100% fetal protection in vaccinates when challenged with a range of diverse antigenic viruses (subgenotypes). There should be a long duration of immunity stimulated by vaccines, especially for fetal protection. MLV vaccines should be safe when given according to the label and free of other pathogens. While vaccines have now included BVDV1a and BVDV2a, with the discovery of the predominate subgenotype of BVDV in the USA to be BVDV1b, approximately 75% or greater in prevalence, protection in acute challenge and fetal protection studies became more apparent for BVDV1b. Thus many published studies examined protection by BVDV1a and BVDV2a vaccines against BVDV1b in acute challenge and fetal protection studies. There are no current BVDV1b vaccines in the USA. There are now more regulations on BVDV reproductive effects by the USDA Center for Veterinary Biologics (CVB) regarding label claims for protection against abortion, PI calves, and fetal infections, including expectations for studies regarding those claims. Also, the USDA CVB has a memorandum providing the guidance for exemption of the warning label statement against the use of the MLV BVDV in pregnant cows and calves nursing pregnant cows. In reviews of published studies in the USA, the results of acute challenge and fetal protection studies are described, including subgenotypes in vaccines and challenge strains and the results in vaccinates and the vaccinates' fetuses/newborns. In general, vaccines provide protection against heterologous strains, ranging from 100% to partial but statistically significant protection. In recent studies, the duration of immunity afforded by vaccines was investigated and reported. Issues of contamination remain, especially since fetal bovine serums may be contaminated with noncytopathic BVDV. In addition, the potential for immunosuppression by MLV vaccines exists, and new vaccines will be assessed in the future to prove those MLV components are not immunosuppressive by experimental studies. As new subgenotypes are found, the efficacy of the current vaccines should be evaluated for these new strains.