Rational Immunogen Design Using Computational Methods

使用计算方法进行合理的免疫原设计

• 批准号: 10273041
• 负责人: Gwo-Yu Chuang
• 金额: $ 24.78万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10273041
• 关键词: Antibodies; Antigens; Complex; Computational Technique; Computing Methodologies; Epitopes; Goals; HIV vaccine; HIV-1; Immune response; Immunodominant Epitopes; Membrane Proteins; Molecular Conformation; Site; Structure; Techniques; Transplantation; Vaccines; Viral; base; design; human pathogen; immunogenicity; iterative design; neutralizing antibody; response; scaffold; success; tool

Significant progress has been made in the rational design of immunogens for an HIV vaccine. Atomic-level structures of viral surface proteins in key functional states, or in complex with neutralizing antibodies, reveal important viral epitopes, providing targets for antibody elicitation. Structure-based computational methods can increase the efficiency, accuracy, and likelihood of success for immunogen design efforts. Specifically, through structural analysis, manipulation, and redesign, we expect a variety of computational techniques to be applied to generate immunogens that focus the immune response: (1) away from undesirably immuno-dominant regions; and (2) towards specific target epitopes. Such rationally designed immunogens are thus expected to enable the elicitation of broadly neutralizing antibodies capable of neutralizing a diverse range of HIV-1 isolates.

HIV疫苗免疫原的合理设计已取得重大进展。处于关键功能状态或与中和抗体复合的病毒表面蛋白的原子水平结构揭示了重要的病毒表位，为抗体引发提供了靶标。基于结构的计算方法可以提高免疫原设计工作的效率、准确性和成功的可能性。具体来说，通过结构分析、操作和重新设计，我们期望应用各种计算技术来生成集中免疫反应的免疫原：（1）远离不需要的免疫优势区域； (2)针对特定的靶表位。因此，这种合理设计的免疫原有望引发能够中和多种HIV-1分离株的广泛中和抗体。