Vaccine Research and Development, Sanofi, Marcy l'Etoile, France.
Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
EBioMedicine. 2024 Oct;108:105332. doi: 10.1016/j.ebiom.2024.105332. Epub 2024 Sep 17.
Yellow fever (YF), a mosquito-borne acute viral haemorrhagic illness, is endemic to many tropical and subtropical areas of Africa and Central and South America. Vaccination remains the most effective prevention strategy; however, as repeated outbreaks have exhausted vaccine stockpiles, there is a need for improved YF vaccines to meet global demand. A live-attenuated YF vaccine candidate (referred to as vYF) cloned from a YF-17D vaccine (YF-VAX®) sub-strain, adapted for growth in Vero cells cultured in serum-free media, is in clinical development. We report the innate and adaptive immune responses and the transcriptome profile of selected genes induced by vYF.
Healthy adults aged 18-60 years were randomised at a 1:1:1:1 ratio to receive one dose of vYF at 4, 5 or 6 Log CCID or YF-VAX (reference vaccine), administered subcutaneously in the upper arm (ClinicalTrials.gov identifier: NCT04142086). Blood/serum samples were obtained at scheduled time points through 180 days (D180) post-vaccination. The surrogate endpoints assessed were: serum cytokine/chemokine concentrations, measured by bead-based Multiplex assay; peripheral blood vYF-specific IgG and IgM memory B cell frequencies, measured by FluoroSpot assay; and expression of genes involved in the immune response to YF-17D vaccination by RT-qPCR.
There was no increase in any of the cytokine/chemokine concentrations assessed through D14 following vaccination with vYF or YF-VAX, except for a slight increase in IP-10 (CXCL10) levels. The gene expression profiles and kinetics following vaccination with vYF and YF-VAX were similar, inclusive of innate (antiviral responses [type-1 interferon, IFN signal transduction; interferon-stimulated genes], activated dendritic cells, viral sensing pattern recognition receptors) and adaptive (cell division in stimulated CD4+ T cells, B cell and antibody) immune signatures, which peaked at D7 and D14, respectively. Increases in vYF-specific IgG and IgM memory B cell frequencies at D28 and D180 were similar across the study groups.
vYF-induced strong innate and adaptive immune responses comparable to those induced by YF-VAX, with similar transcriptomic and kinetic profiles observed.
Sanofi.
黄热病（YF）是一种蚊媒引起的急性病毒性出血热，流行于非洲和中美洲及南美洲的许多热带和亚热带地区。疫苗接种仍然是最有效的预防策略；然而，由于反复爆发耗尽了疫苗库存，因此需要改进黄热病疫苗以满足全球需求。一种从 YF-17D 疫苗（YF-VAX®）亚株克隆的减毒活黄热病疫苗候选物（称为 vYF），适应在无血清培养基中培养的 Vero 细胞中生长，正在进行临床开发。我们报告了 vYF 诱导的固有和适应性免疫反应以及选定基因的转录组谱。
18-60 岁健康成年人按 1:1:1:1 的比例随机接受一次 vYF 剂量，分别为 4、5 或 6 Log CCID 或 YF-VAX（参考疫苗），在上臂皮下接种（临床试验标识符：NCT04142086）。在接种后 180 天（D180）通过预定时间点采集血/血清样本。评估的替代终点包括：通过基于珠子的多重分析测量血清细胞因子/趋化因子浓度；通过 FluoroSpot 分析测量外周血 vYF 特异性 IgG 和 IgM 记忆 B 细胞频率；以及通过 RT-qPCR 测量参与 YF-17D 疫苗接种免疫反应的基因的表达。
除 IP-10（CXCL10）水平略有升高外，接种 vYF 或 YF-VAX 后，通过 D14 评估的任何细胞因子/趋化因子浓度均未增加。接种 vYF 和 YF-VAX 后的基因表达谱和动力学相似，包括固有（抗病毒反应[I 型干扰素、IFN 信号转导；干扰素刺激基因]、激活的树突状细胞、病毒感知模式识别受体）和适应性（受刺激的 CD4+T 细胞、B 细胞和抗体的细胞分裂）免疫特征，分别在 D7 和 D14 达到峰值。在 D28 和 D180，各组之间 vYF 特异性 IgG 和 IgM 记忆 B 细胞频率的增加相似。
vYF 诱导的固有和适应性免疫反应与 YF-VAX 诱导的反应相当，观察到相似的转录组和动力学谱。
赛诺菲。
