NOVEL ANTIGEN DISPLAY SYSTEM TO PRESENT MULTIPLE ANTIGENS AS HIV VACCINES

新型抗原展示系统可呈现多种抗原作为 HIV 疫苗

• 批准号: 8173250
• 负责人: Nancy L Haigwood
• 金额: $ 15.22万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173250
• 关键词: Adjuvant; Antibody Formation; Antigen-Presenting Cells; Antigens; Cellular Immunity; Chimeric Proteins; Complement 3d; Computer Retrieval of Information on Scientific Projects Database; Development; Effectiveness; Engineering; Funding; Grant; HIV; Hybrids; Immunization; Institution; Memory; Methods; N-terminal; Oryctolagus cuniculus; Peptides; Proteins; Recombinants; Regimen; Research; Research Personnel; Resources; Source; System; Tertiary Protein Structure; United States National Institutes of Health; Vaccines; Virus-like particle; base; design; neutralizing antibody; novel; particle; pyruvate dehydrogenase; research study; response; vaccine delivery

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. E2DISP, an engineered protein domain from Geobacillus stearothermophilus pyruvate dehydrogenase subunit E2, can be used to express N-terminal fusions of heterologous peptides or proteins. E2DISP self-assembles into 24 nm virus like particles (VLPs) displaying up to 60 copies of a foreign antigen. (1) Design HIV-E2 Envelope (Env) fusion proteins with conserved neutralization determinants and determine their effectiveness in eliciting neutralizing antibodies (NAbs). (2) Explore immunization strategies to elicit long lasting Th1 CD4, CTL memory responses while preserving sustained antibody responses. (3) Explore optimal presentation and co-administration of E2DISP VLPs with recombinant C3d-based adjuvants. (4) Optimize the use of pure and hybrid E2-HIV VLPs in prime-boost regimens with other vaccine delivery systems effective in boosting cellular immunity and NAb responses. In the last year, we have developed effective methods for purifying and stabilizing pure and hybrid particles. In experiments in rabbits using HIV Env fusion protein 60-mer particles, we have been successful in showing the development of high titers of neutralizing antibodies within only six weeks, after two immunizations. Both the V3 region as well as portions of the gp41 protein elicit neutralizing antibodies in rabbits, and we are exploring the breadth of this response. We are also exploring the delivery of these fusion proteins with microneedle delivery to the mucosal antigen-presenting cells.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 E2DISP是丙酮酸丙酮酸甲状腺醇酚脱氢酶亚基E2的工程蛋白结构域E2，可用于表达异源肽或蛋白质的N末端融合。 E2DISP自组装成24 nm病毒（如颗粒）（VLP），显示出多达60份外抗原的副本。 （1）设计HIV-E2包膜（ENV）融合蛋白具有保守的中和决定因素，并确定它们在启发中和抗体（NABS）方面的有效性。 （2）探索免疫策略以引起持久的TH1 CD4，CTL记忆反应，同时保留持续的抗体反应。 （3）探索E2DISP VLP与基于C3D的佐剂的最佳表现和共同给药。 （4）优化纯和混合E2-HIV VLP在素促进方案中使用其他疫苗递送系统有效提高细胞免疫和NAB反应的方法。 在去年，我们开发了纯化和稳定纯净和混合颗粒的有效方法。 在使用HIV环境融合蛋白60-MER颗粒进行兔子的实验中，我们在两次免疫后仅六周内成功地显示了中和抗体的高滴度的发展。 V3区域以及GP41蛋白的一部分都引起了兔子中和抗体的中和抗体，我们正在探索这种反应的广度。 我们还正在探索这些融合蛋白的递送，并递送微针递送到粘膜抗原呈递细胞。