Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Australia.
PLoS Pathog. 2021 Jan 13;17(1):e1009215. doi: 10.1371/journal.ppat.1009215. eCollection 2021 Jan.
Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya and Zika virus immunogen mRNA and protein expression was associated with necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. The multiple adjuvant signatures at 12 hours post-vaccination were dominated by TLR3, 4 and 9, STING, MAVS, PKR and the inflammasome. Th1 cytokine signatures were dominated by IFNγ, TNF and IL1β, and chemokine signatures by CCL5 and CXCL12. Multiple signatures associated with dendritic cell stimulation were evident. By day seven, vaccine transcripts were absent, and cell death, neutrophil, macrophage and inflammation annotations had abated. No compelling arthritis signatures were identified. Such injection site vaccinology approaches should inform refinements in poxvirus-based vector design.
痘病毒系统已被广泛用作疫苗载体。在此，通过对肌肉内注射部位进行 RNA-Seq 分析，深入了解了宿主固有免疫反应，以及接种新型增殖缺陷型痘苗病毒载体 Sementis Copenhagen Vector 后载体和重组免疫原基因的表达情况。寨卡病毒和基孔肯雅热病毒免疫原的 mRNA 和蛋白表达与坏死的骨骼肌细胞有关，这些细胞被混合细胞浸润物包围。接种后 12 小时的多种佐剂特征主要由 TLR3、4 和 9、STING、MAVS、PKR 和炎症小体主导。Th1 细胞因子特征主要由 IFNγ、TNF 和 IL1β 主导，趋化因子特征主要由 CCL5 和 CXCL12 主导。明显存在与树突状细胞刺激相关的多个特征。到第 7 天，疫苗转录本已不存在，细胞死亡、中性粒细胞、巨噬细胞和炎症注释已经减少。未发现明显的关节炎特征。这种注射部位疫苗学方法应该为痘病毒载体设计的改进提供信息。
