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.

在HIV疫苗的免疫原子的合理设计中取得了重大进展。在关键功能状态下，病毒表面蛋白的原子水平结构，或与中和抗体复杂，揭示了重要的病毒表位，从而为抗体启发提供了靶标。基于结构的计算方法可以提高免疫原设计工作成功的效率，准确性和可能性。具体而言，通过结构分析，操纵和重新设计，我们期望将多种计算技术应用于产生关注免疫反应的免疫原子：（1）远离不可思议的免疫主导区域； （2）朝特定的目标表位。因此，这种合理设计的免疫原被预期能够促进能够中和能够中和各种HIV-1分离株的巨大中和抗体。