Institute of Experimental Immunology, University of Bonn, Bonn, Germany.
Medical Clinic III, University of Bonn, Bonn, Germany.
Front Immunol. 2024 Jan 29;15:1338499. doi: 10.3389/fimmu.2024.1338499. eCollection 2024.
Prophylactic vaccines generate strong and durable immunity to avoid future infections, whereas post-exposure vaccinations are intended to establish rapid protection against already ongoing infections. Antiviral cytotoxic CD8 T cells (CTL) are activated by dendritic cells (DCs), which themselves must be activated by adjuvants to express costimulatory molecules and so-called signal 0-chemokines that attract naive CTL to the DCs.
Here we asked whether a vaccination protocol that combines two adjuvants, a toll-like receptor ligand (TLR) and a natural killer T cell activator, to induce two signal 0 chemokines, synergistically accelerates CTL activation.
We used a well-characterized vaccination model based on the model antigen ovalbumin, the TLR9 ligand CpG and the NKT cell ligand -galactosylceramide to induce signal 0-chemokines. Exploiting this vaccination model, we studied detailed T cell kinetics and T cell profiling in different mouse models of viral infection.
We found that CTL induced by both adjuvants obtained a head-start that allowed them to functionally differentiate further and generate higher numbers of protective CTL 1-2 days earlier. Such signal 0-optimized post-exposure vaccination hastened clearance of experimental adenovirus and cytomegalovirus infections.
Our findings show that signal 0 chemokine-inducing adjuvant combinations gain time in the race against rapidly replicating microbes, which may be especially useful in post-exposure vaccination settings during viral epi/pandemics.
预防性疫苗可产生强大且持久的免疫力，以避免未来的感染，而暴露后疫苗则旨在迅速建立针对正在进行的感染的保护。抗病毒细胞毒性 CD8 T 细胞（CTL）由树突状细胞（DC）激活，而 DC 本身必须通过佐剂激活以表达共刺激分子和所谓的信号 0-趋化因子，从而吸引幼稚 CTL 到 DC。
在这里，我们询问了一种联合使用两种佐剂（一种 Toll 样受体配体（TLR）和一种自然杀伤 T 细胞激活剂）的疫苗接种方案，以诱导两种信号 0 趋化因子，是否能协同加速 CTL 的激活。
我们使用了一种经过充分验证的疫苗接种模型，该模型基于模型抗原卵清蛋白、TLR9 配体 CpG 和 NKT 细胞配体 -半乳糖基神经酰胺来诱导信号 0-趋化因子。利用这种疫苗接种模型，我们研究了不同病毒感染小鼠模型中的详细 T 细胞动力学和 T 细胞谱。
我们发现，两种佐剂诱导的 CTL 获得了先机，使它们能够进一步功能分化，并在 1-2 天内更早地产生更多数量的保护性 CTL。这种信号 0 优化的暴露后疫苗接种加速了实验性腺病毒和巨细胞病毒感染的清除。
我们的发现表明，诱导信号 0 趋化因子的佐剂组合在与快速复制的微生物的竞赛中获得了时间优势，这在病毒爆发期间的暴露后疫苗接种中可能特别有用。
