BDCA1+ mDCs and BDCA3+ mDCs stimulated with vaccines for 6 hr

The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines.

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Banchereau R, Baldwin N, Cepika AM, Athale S, Xue Y, Yu CI, Metang P, Cheruku A, Berthier I, Gayet I, Wang Y, Ohouo M, Snipes L, Xu H, Obermoser G, Blankenship D, Oh S, Ramilo O, Chaussabel D, Banchereau J, Palucka K, Pascual V