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.

中文翻译：

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在绵羊中诱导的 FMDV 疫苗的抗体反应与血液中的早期转录组反应相关。

口蹄疫 (FMD) 是一种高度传染性的病毒性疾病，具有很高的经济影响，是全世界偶蹄哺乳动物的主要威胁。基于佐剂灭活病毒 (iFMDV) 的疫苗可诱导有效的保护性免疫，从而产生抗体 (Ab) 反应。为了减少制造过程的生物安全限制，开发了一种编码 FMDV 抗原的非复制型人类 5 型腺病毒载体 (Ad5-FMDV)。在这里，我们比较了 iFMDV 和 Ad5-FMDV 在绵羊中使用和不使用 ISA206VG 乳液型佐剂的免疫原性。获得了对比的抗体反应：iFMDV 诱导的抗体水平最高，Ad5-FMDV 的抗体水平最低，ISA206VG 增加了 Ad5-FMDV 诱导的抗体对保护水平的反应。每种疫苗都会产生异质性抗体反应，有高反应者和低反应者，后者被认为是疫苗有效性的障碍。对疫苗接种后 24 小时总血液反应的转录组学研究揭示了几种与长期抗体反应相关的血液基因模块活动。T 细胞模块活动的下调与对 iFMDV 和 Ad5-FMDV+ISA206VG 疫苗的高反应相关，这在人类和绵羊的其他系统疫苗学研究中也发现。细胞周期活性的影响取决于疫苗类型，因为它与对 iFMDV 的更高反应呈正相关，但与非佐剂 Ad5-FMDV 呈负相关。最后，24 小时 B 细胞活性升高与对 Ad5-FMDV+ISA206VG 疫苗的高抗体反应相关。