Effect of the vaccination scheme on PregSure® BVD induced alloreactivity and the incidence of Bovine Neonatal Pancytopenia

Abstract

Bovine Neonatal Pancytopenia (BNP) is a new neonate-maternal incompatibility phenomenon caused by vaccine-induced, maternal alloantibodies. The syndrome affects newborn calves at the approximate age of ten days and is characterized by spontaneous bleeding, severe anemia with an almost complete destruction of the red bone marrow. During the past two years the causal role of bioprocess impurities in PregSure(®)BVD, a strongly adjuvanted, inactivated vaccine against Bovine Virus Diarrhoea (BVD), in the induction of BNP causing alloantibodies has clearly been established. Despite intensive research efforts that have elucidated the basic principles of the BNP immunopathology still a number of questions remain open. In the current manuscript we address the puzzling observation that BNP incidences vary widely between different regions: as an example we compare the BNP incidences in the German Federal States of Bavaria and Lower Saxony. In Bavaria the BNP-incidence reaches 100 cases per 100,000 doses PregSure(®)BVD, while in Lower Saxony the incidence is as low as 6 cases per 100,000 doses. In Bavaria the vaccine has always been used according to the instructions for use. By contrast, in Lower Saxony BVD-immunization was performed according to a two-step vaccination protocol including a first immunization with an inactivated BVD-vaccine followed by booster immunizations with a live-attenuated BVD-vaccine. As a consequence, those cattle that received PregSure(®)BVD received in general more than two doses in Bavaria, while in Lower Saxony cows received at maximum one dose. By experimental immunization we can show that the two-step regimen including PregSure(®)BVD as a priming vaccine results in significantly lower alloantibody titers as compared to repetitive immunizations with the inactivated vaccine. The lower alloantibody titer after two-step vaccination explains the lower BNP-incidence in Lower Saxony and - generally speaking - indicates that variations in the vaccination regimen have a great influence on the induction of adverse reactions through bioprocess impurities.