Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study

Jones, Bryony A.; Sauter-Louis, Carola; Henning, Joerg; Stoll, Alexander; Nielen, Mirjam; Van Schaik, Gerdien; Smolenaars, Anja; Schouten, Matthijs; den Uijl, Ingrid; Fourichon, Christine; Guatteo, Raphael; Madouasse, Aurélien; Nusinovici, Simon; Deprez, Piet; De Vliegher, Sarne; Laureyns, Jozef; Booth, Richard; Cardwell, Jackie M.; Pfeiffer, Dirk U.

Despite widespread use of PregSure vaccine prior to its withdrawal, BNP incidence has been low, suggesting that consumption of colostrum from a PregSure-vaccinated dam is not a sufficient cause of BNP. We did not identify any other important calf or management-related risk factors. Research into BNP pathogenesis is on-going with a prevailing hypothesis that it is a neonate-maternal incompatibility phenomenon related to PregSure-induced maternal alloantibodies against bovine cell surface molecules due to bioprocess-related impurities from the cell line used for virus propagation [20] [21] [22] . Bastian et al. [20] showed that sera of dams that had previously had a BNP calf contained alloantibodies that bound to bovine leucocytes, and Foucras et al [23] reproduced BNP in healthy calves by transferring serum antibodies from PregSure-vaccinated dams. Animals vaccinated with three doses of PregSure had higher alloantibody titres compared with animals receiving a single PregSure dose or other BVD vaccines [10] . This supports our finding that the odds of BNP increase with the number of PregSure doses given to the dam. Bridger et al [24] showed that maternal alloantibodies to surface antigens of neonatal leucocytes are transferred via colostrum from BNP dams to neonatal calves, and higher antibody titres in the dam led to more severe clinical signs in the calf. Various proteins found in both PregSure vaccine and the cell line used to produce the vaccine have been implicated as possible alloantigen candidates [21] [22] [23] 25] . Bell et al. [26] suggest that feeding BNP colostrum from multiple cows increases the likelihood that the colostrum will contain antibodies that will react with most calf allotypes, which fits with our finding that calves from unvaccinated dams were at increased risk of BNP if they were fed colostrum from other cows. They suggest that the unique adjuvant in PregSure could amplify production of alloantibody against vaccine antigens as well as boosting pregnancy-induced maternal alloantibodies against paternallyderived foetal MHC antigens [26] . The latter mechanism may explain the aetiology of some of the sporadic cases of unexplained pancytopenia that are not linked to the ingestion of colostrum from PregSure-vaccinated cows.