Rational Immunogen Design Using Computational Methods

在艾滋病毒疫苗免疫原的合理设计方面取得了重大进展。处于关键功能状态或与中和抗体形成复合体的病毒表面蛋白的原子级结构揭示了重要的病毒表位，为抗体激发提供了靶标。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。具体地说，通过结构分析、操作和重新设计，我们希望应用各种计算技术来产生免疫原，使免疫反应(1)远离不受欢迎的免疫突出区域，(2)转向特定的靶标表位。因此，这种合理设计的免疫原有望激发出广泛的中和抗体，中和一系列不同的艾滋病毒-1分离株。

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-prominent regions and (2) towards specific target epitopes. Such rationally designed immunogens are thus expect to enable the elicitation of broadly neutralizing antibodies that neutralize a diverse range of HIV-1 isolates.