PDF(Pubmed)
Abstract：
Plant-based manufacturing has the advantage of post-translational modifications. While plant-specific N-glycans have been associated with allergic reactions, their effect on the specific immune response upon vaccination is not yet understood. In this study, we produced an RBD-Fc subunit vaccine in both wildtype (WT) and glycoengineered (∆XF) Nicotiana benthamiana plants. The N-glycan analysis: RBD-Fc carrying the ER retention peptide mainly displayed high mannose. When produced in WT RBD-Fc displayed complex-type (GnGnXF) N-glycans. In contrast, ∆XF plants produced RBD-Fc with humanized complex N-glycans that lack potentially immunogenic xylose and core fucose residues (GnGn). The three recombinant RBD-Fc glycovariants were tested. Immunization with any of the RBD-Fc proteins resulted in a similar titer of anti-RBD antibodies in mice. Likewise, antisera from subunit RBD-Fc vaccines also demonstrated comparable neutralization against SARS-CoV-2. Thus, we conclude that N-glycan modifications of the RBD-Fc protein have no impact on their capacity to activate immune responses and induce neutralizing antibody production.
摘要：
基于工厂的制造具有翻译后修饰的优点。虽然植物特异性N-聚糖与过敏反应有关，它们对疫苗接种后特异性免疫反应的影响尚不清楚。在这项研究中,我们在野生型（WT）和糖工程（ΔXF）烟草本氏植物中生产了RBD-Fc亚单位疫苗。N-聚糖分析:携带ER保留肽的RBD-Fc主要显示高甘露糖。当在WTRBD-Fc中产生时,展示复合型(GnGnXF)N-聚糖。相比之下,ΔXF植物产生具有人源化复合N-聚糖的RBD-Fc，缺乏潜在的免疫原性木糖和核心岩藻糖残基（GnGn）。测试了三种重组RBD-Fc糖变体。用任何RBD-Fc蛋白的免疫在小鼠中产生相似滴度的抗RBD抗体。同样，来自亚基RBD-Fc疫苗的抗血清也证明了对SARS-CoV-2的相当的中和作用。因此，我们得出结论,RBD-Fc蛋白的N-聚糖修饰对其激活免疫应答和诱导中和抗体产生的能力没有影响.
