From BVD Vaccination to Bleeding Calves - Analysis of the process of pharmacovigilance concerning the PregSure(r) Bovine Virus Diarrhoea Vaccine from Pfizer now known to cause Bovine Neonatal Pancytopenia

Abstract

Bovine Neonatal Pancytopenia is a bleeding disorder occurring in the European Union and New Zealand. The disease affects neonatal or very young calves from PregSure® BVD vaccinated dams. Dams produce alloantibodies against impurities from the MDBK cell line on which PregSure® is produced, including MHC 1, present in PregSure® BVD vaccine. Only dams not recognizing the proteins as self produce those alloantibodies. If a calf produced by such a dam inherits paternal antigens resembling those present in PregSure® BVD and it receives colostrum from its own dam, the alloantibodies present in the sera and colostrum of the dam target the leukocytes, thrombocytes and haematopoietic bone marrow cells of the calf. After binding of the alloantibodies to the cells, the cells undergo phagocytosis through macrophages by complement activation. This results in bone marrow aplasia and haemorrhagic diathesis. Most of the affected calves die, but spontaneous recovery is possible and also subclinical Bovine Neonatal Pancytopenia occurs. The disease Bovine Neonatal Pancytopenia is actually a severe adverse reaction to PregSure® BVD vaccine. This research internship report analyses the process of pharmacovigilance of PregSure® BVD vaccine and follows the developments around the vaccine and the disease through the years. Pharmacovigilance is applied to each veterinary medicine on the market and the process guards the balance between risk and benefits of medicines. Aetiology and pathogenesis of Bovine Neonatal Pancytopenia is investigated thoroughly in the last decade, but still the exact cause of the disease is unknown. It is also not clear which protein or proteins is or are the exact target or targets of the colostrum derived alloantibodies of BNP-dams. Further investigation is necessary because Bovine Neonatal Pancytopenia is the first frequently occurring immunodeficiency caused by a prophylactic measurement like the PregSure® BVD vaccine. Development of the same pathogenesis in the future with other vaccines, human or animal, produced on the same production cell line as the target species can be prevented by extensive knowledge of the pathogenesis and aetiology of Bovine Neonatal Pancytopenia.