Fusion: Vaccine conjugate technology to advance vaccine safety and efficacy

Fusion：疫苗结合技术可提高疫苗的安全性和有效性

• 批准号: 10183150
• 负责人: DAVID Jay BURKHART
• 金额: $ 64.4万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-18 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10183150
• 关键词: Active Sites; Adjuvant; Agonist; Antibodies; Antigen-Presenting Cells; Antigens; Benchmarking; Biological Assay; Cathepsins B; Cells; Cellular Immunity; Chemicals; Conjugate Vaccines; Dendritic Cells; Dose; Early Endosome; Effectiveness; Endosomes; Exposure to; Family suidae; Ha antigen; Human; Immune; Immune response; Immunity; In Situ; In Vitro; Inbred BALB C Mice; Individual; Infection; Inflammation; Influenza A Virus, H7N9 Subtype; Influenza Hemagglutinin; Interferon-alpha; Interleukin-12; Laboratories; Lead; Methods; Miniature Swine; Mus; Peripheral Blood Mononuclear Cell; Process; Prodrugs; Production; Property; Proteins; Recombinant Proteins; Recombinants; Reporter; Research; Site; Specificity; System; T cell response; TLR7 gene; TLR8 gene; TNF gene; Technology; Therapeutic Index; Toll-like receptors; Toxic effect; Vaccine Antigen; Vaccines; Work; chemical conjugate; cost; cytokine; flu; immune activation; immunogenic; immunogenicity; improved; in vivo; in vivo evaluation; influenzavirus; innovation; innovative technologies; next generation; novel; pathogen; patient safety; receptor; response; side effect; vaccine delivery; vaccine efficacy; vaccine safety

Project Abstract The primary objective of this project is to advance technology to improve the safety of vaccines while maintaining or boosting efficacy. By chemically conjugating our novel synthetic TLR7/8 agonists directly to recombinant antigens, our conjugate vaccines provide robust cellular and humoral immune responses with substantially less vaccine side-effects. While conjugated to antigen our adjuvant molecule is in a reduced potency prodrug form, yet still yields a strong cellular and humoral immune response because the adjuvant and antigen are always delivered to the same endosome of dendritic cells. This closely mimics the natural process of pathogen infection much more closely than traditional admixed adjuvant + antigen vaccines whereby cells can be exposed to antigen or adjuvant individually leading to no or low effective immunity and unwanted inflammation. We will further improve the therapeutic index of adjuvant-antigen conjugate vaccines by using linker technology that maintains the adjuvant potency but targeted to the immune cells where it’s needed to reduce potential side-effects.

项目摘要 该项目的主要目的是提高技术以提高疫苗的安全性 同时保持或提高效率。通过化学结合我们的新型合成TLR7/8 激动剂直接用于重组抗原，我们的共轭疫苗提供了可靠的细胞和 疫苗副作用的体液免疫反应大大降低。同时共轭 抗原我们可调节的分子的效力前药形式降低，但仍然产生强大的 细胞和体液免疫反应，因为调整和抗原始终递送 到树突状细胞的同一内体。这紧密模仿了病原体的自然过程 感染比传统的混合辅助 +抗原疫苗更接近细胞 可以暴露于抗原或单独调整无效免疫力，并且 不需要的炎症。我们将进一步改善调整抗原的治疗指数 通过使用维持调整效力但针对性的接头技术共轭疫苗 到需要减少潜在副作用的免疫细胞。