TFH-TARGETING GENETIC ADJUVANTS TO PROMOTE DURABLE ANTI-INFLUENZA STEM ANTIBODIES IN OLDER ADULTS.

靶向 TFH 的基因佐剂可促进老年人产生持久的抗流感干抗体。

• 批准号: 10933286
• 负责人: KENTNER SINGLETON
• 金额: $ 60万
• 依托单位: TENDEL THERAPIES INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2025-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10933286
• 关键词: Address; Adenovirus Vector; Adenoviruses; Adjuvant; Antibodies; Antibody Response; Antigens; CD3 Antigens; Contractor; Elderly; Engineering; Epitopes; Genetic; Hemagglutinin; Human; Influenza; Lead; Licensing; Macaca mulatta; Messenger RNA; Methods; Mus; NIH Vaccine Research Center; Safety; Serotyping; Structure of germinal center of lymph node; Testing; Transfer Agreement; Vaccine Adjuvant; Vaccine Research; Vaccines; Validation; adaptive immune response; aged; anti-influenza; data exchange; flu; immunogenicity; immunoreactivity; influenza virus vaccine; lipid nanoparticle; neutralizing antibody; safety testing; stem; vaccine candidate; vaccine development; vaccine platform; vector

The project is focused on progressing BiTar-s3, a vaccine adjuvant agent. The project will develop a vaccine that targets HA stem epitopes shared across many flu-A strains, thereby addressing the difficulty of eliciting heterosubtypic neutralizing antibodies (nAb) against influenza. Specifically, the project’s aims are constructing immunogens fused to the BiTar-s3 adjuvant, to select a lead vaccine candidate; test safety and immunogenicity of the s3-adjuvanted candidate in mice; and test safety and immunogenicity of the s3-adjuvanted and unadjuvanted vaccine candidate in aged rhesus macaques. Methods will include testing expression and immunoreactivity with anti-HA antibodies of targeted candidate immunogens, engineering the selected immunogen into a high-capacity adenovector, testing the ability of s3 to drive anti-HA stem Tfh and antibody responses, testing safety of the s3-adjuvanted and unadjuvanted vaccines in aged rhesus macaques, evaluating adaptive immune responses, and examining the mechanisms of s3 adjuvant activity in germinal centers.

该项目的重点是进步的BitAR-S3，一种疫苗调节剂。该项目将开发一种针对许多流感菌株共享HA茎表位的疫苗，从而解决了引起异源性中和抗体（NAB）针对影响力的困难。具体而言，该项目的目标是构建与BitAR-S3调节器融合的免疫原，以选择铅疫苗候选者。测试小鼠S3辅助候选者的安全性和免疫原性；在老年恒河猕猴中，S3辅助疫苗候选疫苗的安全性和免疫原性测试安全性和免疫原性。方法将包括测试靶向候选免疫原的抗HA抗体的测试表达和免疫反应性，将所选免疫原（将所选的免疫原）设计成高容量腺苷酸，测试S3驱动抗HA茎TFH和抗体抗体反应的能力，并测试S3添加和未加热的含量的脂肪含量的脂肪含量，并测试了脂肪的含量。免疫调查，并检查生发中心中S3可调活性的机制。