Influenza Vaccines Differentially Regulate the Interferon Response in Human Dendritic Cell Subsets [HumanWG-6 v3.0 Beadchip Experiments]

Human dendritic cells play a fundamental role in the initiation of long-term adaptive immunity during vaccination against influenza. Understanding the early response of human DCs to vaccine challenge is thus essential to determine the nature and magnitude of maturation signals that strongly correlate with vaccine effectiveness. Here, we show that the non-adjuvanted trivalent Fluzone®09-10 (TIV-09) induces monocyte-derived DCs (moDCs), purified blood conventional DCs (cDCs) and plasmacytoid DCs (pDCs) to express CD80, CD83, and CD86, and secrete cytokines. TIV-09 stimulated the secretion of type I interferons (IFN) IFN-α and IFN-β and type III IFN IL-29 by moDCs and cDCs subsets. The vaccine also induced the production of IL-6, TNF and the chemokines IP-10 and MIP-1β. Conversely, the non-adjuvanted monovalent H1N1 California vaccine (MIV-09), which was commercialized in 2009 during the H1N1 epidemics and displayed lower effectiveness in retrospective studies, did not induce the production of type I IFN in moDCs and blood cDCs. Furthermore, it inhibited the TIV-09-induced secretion of type I IFN by these DCs. Yet, both vaccines induced pDCs to secrete type I IFN indicating that different influenza vaccines activate different molecular signaling pathways in different DC subsets. In vivo, the baseline IFN signature was decreased upon administration of the H1N1 vaccine in 3/3 pediatric lupus patients. These results suggest that subtypes of non-adjuvanted influenza vaccines elicit long-term protection through different mechanisms and that a vaccine’s ability to induce an IFN response in DCs may palliate the absence of adjuvant and increase vaccine efficacy. 108 total samples. No replicates. 9 in vitro pDC samples with 3 medium controls; 3 stimulated by non-adjuvanted monovalent H1N1 California vaccine (MIV-09); 3 stimulated by non-adjuvanted trivalent Fluzone®09-10 (TIV-09). 8 in vitro mDC samples with 3 medium controls; 3 stimulated by MIV-09; 2 stimulated by TIV-09. 91 ex vivo whole blood samples with 26 total saline controls at 13 time points with 2 donors; 26 total stimulated by MIV-09 at 13 time points with 2 donors; 39 total stimulated by TIV-09 at 13 time points with 3 donors