Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Curr Opin Immunol. 2020 Aug;65:50-56. doi: 10.1016/j.coi.2020.03.013. Epub 2020 Apr 22.
The recent explosion of atomic-level structures of glycoproteins that comprise the surface antigens of human enveloped viruses, such as RSV, influenza, and HIV, provide tremendous opportunities for rational, structure-based vaccine design. Several concepts in structure-based vaccine design have been put into practice and are are well along preclinical and clinical implementation. Testing of these designed immunogens will provide key insights into the ability to induce the desired immune responses, namely neutralizing antibodies. Many of these immunogens in human clinical trials represent only the first wave of designs and will likely require continued tweaking and elaboration to achieve the ultimate goal of enhanced breadth and potency. Considerable effort is now being invested in germline targeting, epitope focusing, and improved immune presentation such as multivalent nanoparticle incorporation. This review highlights some of the recent advances in these areas as we prepare for the next generation of immunogens for subsequent rounds of iterative vaccine development.
近年来，人类包膜病毒（如 RSV、流感和 HIV）表面抗原糖蛋白的原子级结构大量涌现，为基于结构的理性疫苗设计提供了巨大的机会。一些基于结构的疫苗设计理念已经付诸实践，并在临床前和临床实施方面取得了良好的进展。对这些设计免疫原的测试将为诱导所需免疫反应（即中和抗体）的能力提供关键见解。在人体临床试验中，许多这些免疫原仅代表了第一轮设计，可能需要进一步调整和改进，以实现增强广度和效力的最终目标。目前，人们正在大力进行种系靶向、表位聚焦和改进免疫呈递（如多价纳米颗粒的结合）。本文综述了这些领域的一些最新进展，为我们下一代免疫原的后续迭代疫苗开发做准备。
