Abstract
Foot and mouth disease (FMD) is a highly contagious viral disease with high economic impact, representing a major threat for cloven-hooved mammals worldwide. Vaccines based on adjuvanted inactivated virus (iFMDV) induce effective protective immunity implicating antibody (Ab) responses. To reduce the biosafety constraints of the manufacturing process, a non-replicative human adenovirus type 5 vector encoding FMDV antigens (Ad5-FMDV) has been developed. Here we compared the immunogenicity of iFMDV and Ad5-FMDV with and without the ISA206VG emulsion-type adjuvant in sheep. Contrasted Ab responses were obtained: iFMDV induced the highest Ab levels, Ad5-FMDV the lowest ones, and ISA206VG increased the Ad5-FMDV-induced Ab responses to protective levels. Each vaccine generated heterogeneous Ab responses, with high and low responders, the latter being considered as obstacles to vaccine effectiveness. A transcriptomic study on total blood responses at 24 h post-vaccination revealed several blood gene module activities correlating with long-term Ab responses. Downmodulation of T cell modules’ activities correlated with high responses to iFMDV and to Ad5-FMDV+ISA206VG vaccines as also found in other systems vaccinology studies in humans and sheep. The impact of cell cycle activity depended on the vaccine types, as it positively correlated with higher responses to iFMDV but negatively to non-adjuvanted Ad5-FMDV. Finally an elevated B cell activity at 24 h correlated with high Ab responses to the Ad5-FMDV+ISA206VG vaccine. This study provides insights into the early mechanisms driving the Ab response induced by different vaccine regimens including Ad5 vectors and points to T cell modules as early biomarker candidates of different vaccine-type efficacy across species.
Highlights
The foot and mouth disease virus (FMDV) is a member of the Picornaviridae family, genus Aphthovirus, and is responsible of a contagious vesicular disease affecting cloven-hooved mammals, which has a major impact on animal productions and trade.[1]
On the basis of the serological analysis described above, in the inactivated FMDV (iFMDV) group, we selected the Viral Neutralization Test (VNT) values to perform the correlation: PrioCHECK values were saturated in many instances (Fig. 2), the VNT positivity was almost always confirmed with another test (Table 1), and VNT titers are considered as correlates of protection.[23]
We showed that iFMVD, Ad5-FMDV, and Ad5-FMDV+ISA206 display variable potencies at inducing Ab responses in sheep
Summary
Published in partnership with the Sealy Center for Vaccine Development outbreaks of FMD within and around the European Union member non-responders when negative responses were found in 80% of states have involved sheep.[14]. Highest responses with values well above the positive thresholds in all assays (see Methods), whereas sheep in the Ad5-FMDV group developed weak responses, mainly in the doubtful ranges iFMDV, ad5-FMDV and ad5-FMDV+ISA206VG induce functional transcriptional signatures in blood cells early after vaccination (Fig. 1b–d). On the basis of the serological analysis described above, in the iFMDV group, we selected the VNT values to perform the correlation: PrioCHECK values were saturated in many instances (Fig. 2), the VNT positivity was almost always confirmed with another test (Table 1), and VNT titers are considered as correlates of protection.[23] The area under the curve was calculated for each sheep over one year and used in a PLS analysis with the gene expression fold changes between T0H and T24H, in order to unravel their multivariate relationships with the Ab response. Cell cycle activities at T24H had an opposite effect depending on the vaccine type, being positively correlated with Ab responses to iFMDV and negatively to non-adjuvanted Ad5-FMDV
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
