Instituto René Rachou, Fundação Oswaldo Cruz - FIOCRUZ-Minas, Belo Horizonte, MG, Brazil.
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Sci Rep. 2024 Apr 2;14(1):7709. doi: 10.1038/s41598-024-57645-3.
The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV] and after vaccination (Day 30-45) [Primary Vaccinees, PV]. Data demonstrated high levels of neutralizing antibodies for PV leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV, with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV as compared to NV (532vs398). Moreover, PV exhibited increased levels of Terminal Effector (CD45RACCR7) CD4 and CD8 T-cells and Non-Classical memory B-cells (IgDCD27). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.
本研究旨在评估 YF 特异性中和抗体谱，以及通过单次皮下注射 17DD-YF 疫苗的 1/5 分数剂量引发的细胞介导反应的表型/功能特征的多参数分析。在两个时间点监测每个志愿者的免疫参数，称为：之前（第 0 天）[未接种，NV]和接种后（第 30-45 天）[初级接种者，PV]。数据表明，PV 的中和抗体水平很高，导致血清阳性率为 93%。还观察到 PV 中系统性可溶性介质的广泛增加，呈混合特征，IFN-γ 和 TNF-α 呈现出最高的基线倍数变化。可溶性介质的综合网络映射显示，与 NV 相比，PV 的相关性数量增加（532 对 398）。此外，与 NV 相比，PV 表现出更高水平的终末效应（CD45RACCR7）CD4 和 CD8 T 细胞和非经典记忆 B 细胞（IgDCD27）。质谱流式细胞术数据的降维进一步支持了这些发现。观察到 T 和 B 细胞的细胞因子谱（TNF-α/IFN-γ/IL-10/IL-17/IL-2）具有多功能性。PV 的可溶性介质特征图谱和动力学时间线进一步证实了长期体外培养中的多功能谱，这是由 IFN-γ 和 TNF-α 水平增加以及 IL-10 产量减少介导的。这些发现为 17DD-YF 疫苗的 1/5 分数剂量引发的保护相关因素提供了新的见解。
