Monitoring the immune response to vaccination with an inactivated vaccine associated to bovine neonatal pancytopenia by deep sequencing transcriptome analysis in cattle

Abstract

Bovine neonatal pancytopenia (BNP) is a new fatal, alloimmune/alloantibody mediated disease of new-born calves induced by ingestion of colostrum from cows, which had been vaccinated with a specific vaccine against the Bovine Virus Diarrhoea Virus (BVDV). The hypothesis of pathogenic MHC class I molecules in the vaccine had been put up, but no formal proof of specific causal MHC class I alleles has been provided yet. However, the unique features of the vaccine obviously result in extremely high specific antibody titres in the vaccinated animals, but apparently also in further molecules inducing BNP. Thus, a comprehensive picture of the immune response to the vaccine is essential. Applying the novel approach of next generation RNA sequencing (RNAseq), our study provides a new holistic, comprehensive analysis of the blood transcriptome regulation after vaccination with the specific BVDV vaccine. Our RNAseq approach identified a novel cytokine-like gene in the bovine genome that is highly upregulated after vaccination. This gene has never been described before in any other species and might be specific to ruminant immune response. Furthermore, our data revealed a very coordinated immune response to double-stranded (ds) RNA or a dsRNA analogue after vaccination with the inactivated single-stranded (ss) RNA vaccine. This would suggest either a substantial contamination of the vaccine with dsRNA from host cells after virus culture or a dsRNA analogue applied to the vaccine. The first option would highlight the potential risks associated with virus culture on homologous cells during vaccine production; the latter option would emphasise the potential risks associated with immune stimulating adjuvants used in vaccine production.

Impact of three inactivated bovine viral diarrhoea virus vaccines on bulk milk p80 (NS3) ELISA test results in dairy herds

“…The BM antibody test results against whole BVDV were not significantly different between Bovidec and Bovilis BVD vaccines, suggesting that the differences observed in the Pourquier p80 ELISA were specific to the vaccine brand. The elevated antibody reactivity against whole BVDV observed with the PregSure BVD vaccine is possibly due to increased immunogenicity associated with the specific adjuvant used in this vaccine (Demasius et al, 2013). The PregSure BVD vaccine has recently been withdrawn, due to links with neonatal pancytopenia in calves (Deutskens et al, 2011;Euler et al, 2013).…”

Different Blood Cell-Derived Transcriptome Signatures in Cows Exposed to Vaccination Pre- or Postpartum

“…Animals, sampling and data collection were identical to those described in our previous study [19]. The study included six lactating and six non-lactating cows ( Table 1).…”

“…Comparative transcriptional profiling of bovine blood leucocytes and macrophages in response to infection using RNAseq and gene expression microarrays showed that RNAseq is superior in detecting differential gene expression because of its increased dynamic range [17,18]. Recently, we demonstrated that RNAseq analysis is remarkably applicable for monitoring the immune response in whole blood of cows subjected to an antigen challenge [19]. The results of our study provided a comprehensive catalogue of transcripts expressed in whole bovine blood and identified transcripts differentially expressed in response to the antigen challenge.…”

“…The focus of this study was to elucidate the influence of the antigen challenge on the transcriptional modulation of the immune response in cows differing regarding lactation status to monitoring the regulatory transcriptional processes reflected in the whole blood of these cows. Therefore, we performed a follow-up investigation based on our previous whole transcriptome RNAseq dataset [19]. We hypothesized that an efficient immune response to antigen challenge is dependent on the specific metabolic status of the cows around calving and postulated that differences in the immune response are reflected at transcriptional level in blood cells of preand post-calving cows.…”

Generation and characterization of the blood transcriptome of Macaca thibetana and comparative analysis with M. mulatta

“…13,14 The blood transcriptome has been widely studied for molecular and cellular profiling of the human immune response. 18 In primates, transcriptomic studies have been published for several model species, including 2 macaques: the rhesus macaque (M. mulatta) and the cynomolgus macaque (M. fascicularis). 18 In primates, transcriptomic studies have been published for several model species, including 2 macaques: the rhesus macaque (M. mulatta) and the cynomolgus macaque (M. fascicularis).…”