Abstract
A mysterious disease affecting calves, named bovine neonatal pancytopenia (BNP), emerged in 2007 in several European countries. Epidemiological studies revealed a connection between BNP and vaccination with an inactivated vaccine against bovine virus diarrhea (BVD). Alloantibodies reacting with blood leukocytes of calves were detected in serum and colostrum of dams, which have given birth to calves affected by BNP. To understand the linkage between vaccination and the development of alloantibodies, we determined the antigens reacting with these alloantibodies. Immunoprecipitation of surface proteins from bovine leukocytes and kidney cells using sera from dams with a confirmed case of BNP in their gestation history reacted with two dominant protein species of 44 and 12 kDa. These proteins were not detected by sera from dams, free of BVDV and not vaccinated against BVD, and from sera of animals vaccinated with a different inactivated BVD vaccine. The 44 kDa protein was identified by mass spectrometry analysis as MHC I, the other as β-2-microglobulin. The presence of major histocompatibility complex class I (MHC I) in the vaccine was confirmed by Western blot using a MHC I specific monoclonal antibody. A model of BNP pathogenesis is proposed.
Highlights
A mysterious hemorrhagic disease of cattle emerged in 2007 affecting solely newborn calves [1]
Precipitation of cell surface antigens from Mabin-Darby bovine kidney (MDBK) cells with bovine neonatal pancytopenia (BNP)-dam sera It has recently been described that BNP alloantibodies react with intact leukocytes of susceptible calves [20,21,22]
It appeared likely that the induction of alloantibodies by the PregSure® bovine virus diarrhea (BVD) vaccine is due to antigen(s) derived from bovine kidney cells that are described for propagation of the vaccine virus
Summary
A mysterious hemorrhagic disease of cattle emerged in 2007 affecting solely newborn calves [1]. First named “blood sweating”, “hemorrhagic diathesis” and “bleeding calf syndrome” it was designated “bovine neonatal pancytopenia” (BNP) at the Satellite Symposium of the European Buiatric Congress in 2009 [2]. During the last years an increasing number of calves were affected by this syndrome. BNP cases were reported for several breeds and both genders are affected . Reports of BNP affected calves are known from several European countries including France, Germany, United Kingdom, Ireland, Netherlands, Belgium, Luxembourg, Italy, and Spain [2,3]. The disease is unknown in countries which do not vaccinate against bovine virus diarrhea virus (BVDV) like Denmark, Austria, and Switzerland [4]
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