Systems vaccinology analysis of a recombinant vaccinia-based vector reveals diverse innate immune signatures at the injection site

Abstract

Poxvirus systems have been extensively used as vaccine vectors. Herein a systems vaccinology analysis of intramuscular injection sites provides 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. 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 innate systems vaccinology approaches should inform refinements in poxvirus-based vector design.

An inconvenient association between granzyme A and Nicotinamide Nucleotide Transhydrogenase

“…GzmA -/and 6J mice were infected with CHIKV, feet collected on day 6 and RNA samples prepared as described previously (Wilson et al, 2017). Library preparation and sequencing were conducted by the Australian Genome Research Facility (Melbourne, Australia) as described (Hazlewood et al, 2021). Briefly, cDNA libraries were prepared using a TruSeq RNA Sample Prep Kit (v2) (Illumina Inc. San Diego, USA), which included isolation of poly-adenylated RNA using oligo-dt beads.…”