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首页> 外文会议>Cell culture engineering conference >HIV-1 ENVELOPE VACCINE PRODUCTION WITH IMPROVED YIELDS AND GLYCOSYLATION PROFILE THROUGH MANNOSE SUPPLEMENTATION
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HIV-1 ENVELOPE VACCINE PRODUCTION WITH IMPROVED YIELDS AND GLYCOSYLATION PROFILE THROUGH MANNOSE SUPPLEMENTATION

机译：通过补给甘露糖来提高HIV-1信封疫苗产量和糖基化特性

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A long-standing goal of the HIV field has been to develop a vaccine; however, there has been limited success in this pursuit, to date. The HIV-1 envelope glycoprotein (Env) is the only HIV viral protein known to elicit broadly neutralizing antibodies (bNAbs) and as such Env is the only candidate molecule for vaccine design. Recent advances have been made for stable expression of this recombinant protein in its closed, pre-fusion native viral surface conformation, with the current work focusing on the BG505-DS-SOSIP.664 construct developed at the NIH. The HIV-1 Env is a trimeric construct containing approximately 90 N-linked glycans accounting for over 50% of the protein mass. This glycan profile is an essential determinant for viral infection, with Env having a predominantly oligomannose glycan composition. Specific glycans are utilized for the binding epitopes of several bNAbs, indicating the importance of the glycosylation profile in a potential vaccine candidate. Utilizing DoE principles, a media supplement screen was carried out in shake flasks and ambr®15 micro bioreactors to investigate magnesium and manganese cations, monosaccharides, and higher nutrient supplementation on the Env glycosylation profile. These screens identified that supplementation with mannose could significantly improve the quantity and quality of the recombinant protein, but other nutrient feeds and hexose sugars, such as glucose or fructose, did not provide a similar benefit. Glycan profile analysis confirmed that the benefit of mannose can be attributed to the shift in the glycan profile to increased oligomannose species. Additional studies are planned to optimize the mannose and other monosaccharide supplementations with the ultimate goal to incorporate the results into a GMP manufacturing process.
机译：HIV领域的长期目标是开发疫苗。然而，迄今为止，这种追求的成功有限。 HIV-1包膜糖蛋白（Env）是已知引起广泛中和抗体（bNAbs）的唯一HIV病毒蛋白，因此Env是疫苗设计的唯一候选分子。该重组蛋白以其封闭的融合前天然病毒表面构象稳定表达的最新进展，目前的工作集中在NIH开发的BG505-DS-SOSIP.664构建体上。 HIV-1 Env是三聚体构建体，包含约90个N-连接的聚糖，占蛋白质质量的50％以上。该聚糖谱是病毒感染的重要决定因素，其中Env主要具有低聚甘露糖聚糖组成。特异性聚糖被用于几种bNAb的结合表位，表明糖基化谱在潜在的候选疫苗中的重要性。利用DoE原理，在摇瓶和ambr®15微型生物反应器中进行了培养基补充筛选，以研究Env糖基化曲线上的镁和锰阳离子，单糖和更高的营养补充。这些筛查结果表明，补充甘露糖可以显着改善重组蛋白的数量和质量，但是其他营养饲料和己糖（例如葡萄糖或果糖）并没有提供类似的益处。聚糖谱分析证实，甘露糖的益处可归因于聚糖谱向增加的低聚甘露糖种类的转变。计划进行其他研究，以优化甘露糖和其他单糖的补充，最终目的是将结果纳入GMP制造过程。

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