Research ArticleVaccines

Influenza vaccines differentially regulate the interferon response in human dendritic cell subsets

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Science Translational Medicine  22 Mar 2017:
Vol. 9, Issue 382, eaaf9194
DOI: 10.1126/scitranslmed.aaf9194

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Influenz-ing interferon responses in dendritic cells

Seasonal influenza vaccines have been produced and marketed for decades but are not always protective. Athale et al. tested a trivalent vaccine that outperformed the monovalent vaccine made by the same manufacturer for the ability to activate human dendritic cell subsets, which are crucial for launching adaptive immune responses. They discovered that both vaccines could activate plasmacytoid dendritic cells, but only the trivalent vaccine could induce antiviral interferon responses in other types of dendritic cells. Moreover, people immunized with the monovalent vaccine did not show early interferon responses in the blood, which were induced by trivalent vaccination. These intriguing results may help explain vaccine underperformance that is not due to antigenic mismatch.

Abstract

Human dendritic cells (DCs) 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 exposure is thus essential to determine the nature and magnitude of maturation signals that have been shown to strongly correlate with vaccine effectiveness. In 2009, the H1N1 influenza epidemics fostered the commercialization of the nonadjuvanted monovalent H1N1 California vaccine (MIV-09) to complement the existing nonadjuvanted trivalent Fluzone 2009–2010 vaccine (TIV-09). In retrospective studies, MIV-09 displayed lower effectiveness than TIV-09. We show that TIV-09 induces monocyte-derived DCs (moDCs), 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 (IFNs) IFN-α and IFN-β and type III IFN interleukin-29 (IL-29) by moDC and cDC subsets. The vaccine also induced the production of IL-6, tumor necrosis factor, and the chemokines IFN-γ–inducible protein 10 (IP-10) and macrophage inflammatory protein–1β (MIP-1β). Conversely, MIV-09 did not induce the production of type I IFNs in moDCs and blood cDCs. Furthermore, it inhibited the TIV-09–induced secretion of type I IFNs by these DCs. However, both vaccines induced pDCs to secrete type I IFNs, indicating that different influenza vaccines activate distinct molecular signaling pathways in DC subsets. These results suggest that subtypes of nonadjuvanted influenza vaccines trigger immunity through different mechanisms and that the ability of a vaccine to induce an IFN response in DCs may offset the absence of adjuvant and increase vaccine efficacy.

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