Karoina Palcka
The mechanisms through which microbial vaccines interact with human APCs are still unknown. The transcriptional programmes induced in human DCs by pathogens, innate receptor ligands, and vaccines are described here. We were able to construct a modular framework containing 204 transcript clusters after exposing DCs to influenza, Salmonella enterica, and Staphylococcus aureus. This framework is used to characterise the responses of 13 vaccines to human monocytes, monocyte-derived DCs, and blood DC subsets. Depending on the pathogen, adjuvant formulation, and APC targeted, different vaccines induce distinct transcriptional programmes. Fluzone, Pneumovax, and Gardasil, in turn, activate monocyte-derived DCs, monocytes, and CD1c+ blood DCs, highlighting the importance of APC specialization in vaccine response. Finally, blood signatures from people who have been vaccinated with Fluzone or who have been infected with influenza show a signature of adaptive immunity activation after vaccination and symptomatic infections, but not asymptomatic infections. These data, which are accessible via a web interface, may aid in the development of better vaccines.