Abstract
BackgroundBovine neonatal pancytopenia (BNP) is a disease syndrome in newborn calves of up to four weeks of age, first observed in southern Germany in 2006. By now, cases have been reported in several countries around the globe. Many affected calves die within days due to multiple haemorrhages, thrombocytopenia, leukocytopenia and bone marrow depletion. A certain vaccine directed against Bovine Virus Diarrhoea Virus (BVDV) was recently shown to be associated with BNP pathogenesis. Immunized cows develop alloantibodies that are transferred to newborn calves via colostrum intake. In order to further elucidate BNP pathogenesis, the purpose of this study was to characterize and compare the protein composition of the associated vaccine to another vaccine directed against BVDV not related to BNP and the cell surface proteome of MDBK (Madin-Darby Bovine Kidney) cells, the cell line used for production of the associated vaccine.ResultsBy SDS-PAGE and mass spectrometry, we were able to detect several coagulation-related and immune modulatory proteins, as well as cellular and serum derived molecules being shared between the associated vaccine and MDBK cells. Furthermore, the number of proteins identified in the BNP related vaccine was almost as high as the number of surface proteins detected on MDBK cells and exceeded the amount of proteins identified in the non-BNP related vaccine over 3.5 fold. The great amount of shared cellular and serum derived proteins confirm that the BNP associated vaccine contained many molecules originating from MDBK cells and vaccine production.ConclusionsThe respective vaccine was not purified enough to prevent the development of alloantibodies. To narrow down possible candidate proteins, those most likely to represent a trigger for BNP pathogenesis are presented in this study, giving a fundament for further analysis in future research.
Highlights
Bovine neonatal pancytopenia (BNP) is a disease syndrome in newborn calves of up to four weeks of age, first observed in southern Germany in 2006
BNP associated Bovine Viral Diarrhoea (BVD) vaccine contains a variety of different proteins First evaluation of protein composition of different BVD vaccines showed a clear difference between vaccine B (Figure 1B) and A (Figure 1C)
We provide the first characterization of Madin-darby bovine kidney (MDBK) cell surface proteome and the proteomes of two BVD vaccines
Summary
Bovine neonatal pancytopenia (BNP) is a disease syndrome in newborn calves of up to four weeks of age, first observed in southern Germany in 2006. Bovine neonatal pancytopenia (BNP) is a disease transferred by colostral alloantibodies binding to peripheral blood-derived leukocytes and platelet antigens of calves [1]. Calves develop a severe thrombocytopenia and leukocytopenia within few hours after passive transfer of colostral antibodies to blood and die within several days from bleeding disorder and bone marrow depletion [1,2]. Respective alloantibodies responsible for BNP can develop in cows previously vaccinated with a specific Bovine Viral Diarrhoea (BVD) vaccine (PregSure BVD; Pfizer, Berlin, Germany; vaccine A) [1]. The antigen(s) appear(s) to be expressed on mature PBL as Assad et al demonstrated binding of colostrum-derived antibodies to several PBL subsets and platelets [3], and further on hematopoietic progenitor cells of the myeloid and lymphoid lineages in the bone marrow, as these are, according to Laming et al, comprised already 24 hours after colostrum intake and show a drastic decline within the first 6 days after colostrum intake [6]
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