PDF(Pubmed)
Abstract：
A key aspect of successful viral vaccine design is the elicitation of neutralizing antibodies targeting viral attachment and fusion glycoproteins that embellish viral particles. This observation has catalyzed the development of numerous viral glycoprotein mimetics as vaccines. Glycans can dominate the surface of viral glycoproteins and as such, the viral glycome can influence the antigenicity and immunogenicity of a candidate vaccine. In one extreme, glycans can form an integral part of epitopes targeted by neutralizing antibodies and are therefore considered to be an important feature of key immunogens within an immunization regimen. In the other extreme, the existence of peptide and bacterially expressed protein vaccines shows that viral glycosylation can be dispensable in some cases. However, native-like glycosylation can indicate native-like protein folding and the presence of conformational epitopes. Furthermore, going beyond native glycan mimicry, in either occupancy of glycosylation sites or the glycan processing state, may offer opportunities for enhancing the immunogenicity and associated protection elicited by an immunogen. Here, we review key determinants of viral glycosylation and how recombinant immunogens can recapitulate these signatures across a range of enveloped viruses, including HIV-1, Ebola virus, SARS-CoV-2, Influenza and Lassa virus. The emerging understanding of immunogen glycosylation and its control will help guide the development of future vaccines in both recombinant protein- and nucleic acid-based vaccine technologies.
摘要：
成功的病毒疫苗设计的一个关键方面是引发靶向病毒附着和修饰病毒颗粒的融合糖蛋白的中和抗体。这一观察结果催化了许多病毒糖蛋白模拟物作为疫苗的开发。聚糖可以支配病毒糖蛋白的表面，因此，病毒糖可影响候选疫苗的抗原性和免疫原性。在一个极端,聚糖可以形成中和抗体靶向的表位的组成部分，因此被认为是免疫方案中关键免疫原的重要特征。在另一个极端,肽和细菌表达的蛋白质疫苗的存在表明，在某些情况下，病毒糖基化是可有可无的。然而,天然样糖基化可以指示天然样蛋白质折叠和构象表位的存在。此外，超越了天然的聚糖模仿，在糖基化位点的占用或聚糖加工状态中，可以提供增强由免疫原引发的免疫原性和相关保护的机会。这里,我们回顾了病毒糖基化的关键决定因素，以及重组免疫原如何在一系列包膜病毒中概括这些特征，包括HIV-1，埃博拉病毒，SARS-CoV-2、流感和拉沙病毒。对免疫原糖基化及其控制的新认识将有助于指导基于重组蛋白质和核酸的疫苗技术的未来疫苗的开发。
