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: 10402889
• 负责人: DAVID Jay BURKHART
• 金额: $ 60.05万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402889
• 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 该项目的主要目标是推进技术以提高疫苗的安全性 同时通过化学结合我们的新型合成 TLR7/8 来维持或提高功效。 直接针对重组抗原的激动剂，我们的结合疫苗提供强大的细胞和 体液免疫反应与疫苗副作用大大减少。 抗原我们的佐剂分子是效力降低的前药形式，但仍然产生强大的 细胞和体液免疫反应，因为佐剂和抗原总是被递送 到树突状细胞的相同内体，这非常模仿病原体的自然过程。 与传统的混合佐剂+抗原疫苗相比，感染更加紧密，因此细胞 可以单独暴露于抗原或佐剂，导致没有或低有效免疫力 我们将进一步提高佐剂抗原的治疗指数。 通过使用接头技术来维持佐剂效力但具有针对性的结合疫苗 到需要减少潜在副作用的免疫细胞。

项目成果

Self-Adjuvanting TLR7/8 Agonist and Fentanyl Hapten Co-Conjugate Achieves Enhanced Protection against Fentanyl Challenge.

自我辅助 TLR7/8 激动剂和芬太尼半抗原共轭物可增强针对芬太尼挑战的保护。

• 发表时间: 2023-10-18
• 影响因子: 4.7
• 作者: Powers, Noah;Massena, Casey;Crouse, Bethany;Smith, Mira;Hicks, Linda;Evans, Jay T;Miller, Shannon;Pravetoni, Marco;Burkhart, David
• 通讯作者: Burkhart, David

A tractable covalent linker strategy for the production of immunogenic antigen-TLR7/8L bioconjugates.

用于生产免疫原性抗原-TLR7/8L 生物缀合物的易处理的共价接头策略。

• 发表时间: 2021-05-11
• 作者: Massena, C J;Lathrop, S K;Davison, C J;Schoener, R;Bazin, H G;Evans, J T;Burkhart, D J
• 通讯作者: Burkhart, D J