Abstract
Rift Valley fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVF vaccine, authentic recombinant MP-12 (arMP-12). From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with arMP-12. While the serology and protective response induced by arMP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood of vaccinated calves over a time course of 21 days before and after vaccination with arMP-12. The time course RNAs were sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to the vaccine induced immune response and its regulation. Additional bioinformatic analyses identified a correlative relationship between specific host immune response genes and protective immunity prior to the detection of protective serum neutralizing antibody responses. These results contribute an important proof of concept for identifying molecular and genetic components underlying the immune response to RVF vaccination and protection prior to serologic detection.
Highlights
Rift Valley fever Virus (RVFV) is a segmented, negative-stranded RNA virus and the causative agent of the vector-borne zoonotic disease, Rift Valley fever (RVF)
We reported a rapid immune response with high serum neutralizing antibody titers as measured by the plaque reduction neutralizing test (PRNT80), and a strong longterm immune response measured by a RVFV antigen-specific IgG enzyme-linked immunosorbent assay (ELISA) induced by authentic recombinant MP-12 in both pregnant sheep and cattle [15,16,17]
We developed a dynamic Bayesian network (DBN) modeling approach [47] to use as a predictive model of the PRNT80 protective immune response from the highly correlated gene expression found present in a selected set of corresponding sliding window correlation (SWC) correlated pathways and gene ontology (GO) terms
Summary
Rift Valley fever Virus (RVFV) (family Bunyaviridae, genus Phlebovirus) is a segmented, negative-stranded RNA virus and the causative agent of the vector-borne zoonotic disease, Rift Valley fever (RVF). The initial outbreak of RVF occurred in 1931 in the Rift Valley of Kenya in sheep, cattle and humans [1]. RVFV is considered endemic across Africa from Mauritania and Senegal in the west, Mozambique, South Africa and Namibia in the south, and PLOS ONE | DOI:10.1371/journal.pone.0147027. Libraries and the Office of the Vice President for Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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