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

ABSTRACT: 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-1β (IL-1β) 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-1β to CD8⁺ T cells. Using this approach, we demonstrate safe inclusion of IL-1β 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-1β-based vaccine adjuvants and also provides further insight in the mechanics of cellular immune responses driven by IL-1β.

SUBMITTER: Van Den Eeckhout B

PROVIDER: S-EPMC7378068 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Specific targeting of IL-1β activity to CD8<sup>+</sup> T cells allows for safe use as a vaccine adjuvant.

Van Den Eeckhout Bram B Van Hoecke Lien L Burg Elianne E Van Lint Sandra S Peelman Frank F Kley Niko N Uzé Gilles G Saelens Xavier X Tavernier Jan J Gerlo Sarah S

NPJ vaccines 20200723 1

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-1β (IL-1β) 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 aro ...[more]

PMID: 32714571

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Project description:Background and aimHuman papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools.MethodsInitially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8+ T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8+, nested interferon gamma (IFN-γ)-producing CD4+, and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes.ResultsTwenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from -10.80 to -86.71 kcal/mol. In addition, CD8+ epitope-overlapped segments in CD4+ and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways.ConclusionEven though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8+ and overlapped epitopes provide new insights into HPV vaccine development.

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

Publications

Specific targeting of IL-1β activity to CD8<sup>+</sup> T cells allows for safe use as a vaccine adjuvant.

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

Publications

Specific targeting of IL-1β activity to CD8<sup>+</sup> T cells allows for safe use as a vaccine adjuvant.

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OmicsDI is part of the ELIXIR infrastructure

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