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

Effect of the vaccination scheme on PregSure®BVD induced alloreactivity and the incidence of Bovine Neonatal Pancytopenia
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DOI:
10.1016/j.vaccine.2012.08.069
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发表时间:
2012-10-19
期刊:
影响因子:
5.5
通讯作者:
Bastian, Max
Bastian, Max
中科院分区:
医学3区
文献类型:
--
作者:
Kasonta, Rahel;Sauter-Louis, Carola;Bastian, Max

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牛新生儿全血细胞减少症(BNP)是由疫苗诱导的母体同种异体抗体引起的一种新的新生儿-母体不相容现象。该综合征影响大约10天大的新生牛犊,其特征是自发出血,严重贫血,几乎完全破坏红色骨髓。在过去两年中,一种强佐剂牛病毒腹泻(BVD)灭活疫苗pressure (R) BVD中的生物过程杂质在诱导BNP引起同种异体抗体中的因果作用已经明确确立。尽管密集的研究工作已经阐明了BNP免疫病理的基本原理,但仍有许多问题尚未解决。在目前的手稿中,我们解决了BNP发病率在不同地区之间差异很大的令人困惑的观察:作为一个例子,我们比较了德国巴伐利亚州和下萨克森州的BNP发病率。在巴伐利亚州,每10万剂压力(R) BVD的发病率达到100例,而在下萨克森州,发病率低至每10万剂6例。在巴伐利亚州,疫苗一直按照使用说明使用。相比之下,在下萨克森州,bvd免疫接种是根据两步接种方案进行的,包括首先接种bvd灭活疫苗,然后接种bvd减毒活疫苗加强免疫。因此,在巴伐利亚州,那些接受了pressure sure (R) BVD的牛一般接受了两剂以上的剂量,而在下萨克森州,奶牛最多只接受了一剂。通过实验免疫,我们可以证明,与使用灭活疫苗重复免疫相比,包括pressure (R) BVD作为启动疫苗的两步方案可显著降低同种异体抗体滴度。两步接种后同种抗体滴度较低解释了下萨克森州bnp发病率较低的原因,一般来说,这表明接种方案的变化对通过生物过程杂质诱导不良反应有很大影响。(C) 2012 Elsevier Ltd.版权所有。
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 (R) 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 (R) 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 (R) 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 (R) 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. (C) 2012 Elsevier Ltd. All rights reserved.