Specific targeting of IL-1ß activity to CD8+ T cells allows for safe use as a vaccine adjuvant

Annual administration and reformulation of influenza vaccines is required for protection against seasonal infections. However, the induction of strong and long-lasting T cells is critical to reach broad and potentially lifelong antiviral immunity. The NLRP3 inflammasome and its product interleukin-1ß (IL-1ß) are pivotal mediators of cellular immune responses to influenza, yet, overactivation of these systems leads to side effects, which hamper clinical applications. Here, we present a bypass around these toxicities by targeting the activity of IL-1ß to CD8+ T cells. Using this approach, we demonstrate safe inclusion of IL-1ß as an adjuvant in vaccination strategies, leading to full protection of mice against a high influenza virus challenge dose by raising potent T cell responses. In conclusion, this paper proposes a class of IL-1ß-based vaccine adjuvants and also provides further insight in the mechanics of cellular immune responses driven by IL-1ß. Overall design: Groups: WIV alone (reference)/WIV+AddaVax (positive control)/WIV+WT IL-1b/WIV+CD8a ALN-1 Tissues/group: lungs and mediastinal lung-draining lymph nodes Biological replicates/group: 3 Samples in total: 23 Sequencing: Illumina NextSeq500 High Output 75 (two single-end runs/sample) contributor: VIB Flow Core contributor: VIB Nucleomics Core