Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures.

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.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: NAP, LL and JDH own Sementis shares. JDH is the current CSO of Sementis. AS was a consultant for Sementis. PMH was the previous CEO/CSO of Sementis. LL and NAP have had, and/or currently have, salary and/or project support from funds provided, whole or in part, via Sementis. Sementis had no role in the design and interpretation of the study, or in preparation of the manuscript.