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

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 non-adjuvanted monovalent H1N1 California vaccine (MIV-09) to complement the existing non-adjuvanted trivalent Fluzone®09–10 vaccine (TIV-09). In retrospective studies, MIV-09 displayed lower effectiveness than TIV-09. Here, 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 (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, MIV-09 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 distinct molecular signaling pathways in DC subsets. These results suggest that subtypes of non-adjuvanted 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.

Efficient Targeting and Activation of Antigen-Presenting Cells In Vivo after Modified mRNA Vaccine Administration in Rhesus Macaques

“…Comparison of trivalent versus monovalent seasonal influenza vaccines showed that the more potent trivalent vaccine also induced stronger type I IFN responses in vaccinated individuals. 47 While HA-specific antibodies confer protection for influenza, other infections may require a stronger polyfunctional Th1 CD4 + T cell response than observed in this study. Whether this can be achieved by co-formulating the mRNA vaccine with a strong Th1 skewing adjuvant like poly I:C remains to be explored.…”

Inflammatory Mediator Expression Associated With Antibody Response Induced by Live Attenuated vs Inactivated Influenza Virus Vaccine in Children

“…Several studies support an association between the ability of a vaccine to induce an interferon response and VE [ 6 , 7 , 15 , 27 ]. Cao reported that IFN-stimulated genes were increased early postvaccination (day 1) but were elevated later (day 7) following LAIV vaccination.…”

Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection

“…Recent and current studies are increasingly highlighting the significance of studying immune cells and responses at the site of infection (86)(87)(88)(89). Our study describes the susceptibility and response of human PDCs from two different anatomical compartments to in vitro IAV infection.…”