Borhani Shayan G, Levine Max Z, Krumpe Lauren H, Wilson Jennifer, Henrich Curtis J, Oâ Keefe Barry R, Lo Donald, Sittampalam G Sitta, Godfrey Alexander G, Lunsford R Dwayne, Mangalampalli Venkata, Tao Dingyin, LeClair Christopher A, Thole Aaron, Frey Douglas, Swartz James, Rao Govind
bioRxiv. 2022 Dec 20:2022.12.19.521044. doi: 10.1101/2022.12.19.521044.
This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstrated against SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressed . The proposed production process is efficient and can be readily scaled up and deployed anywhere in the world where a viral pathogen might emerge. The current emergence of viral variants has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.
本研究描述了一种广谱抗病毒蛋白——格里菲斯菌素(GRFT)的无细胞生物制造方法,使其能够在不到24小时内以一致的纯度和效力生产出来。我们展示了使用两个独立的无细胞系统(一个植物系统和一个微生物系统)生产GRFT的过程。使用标准的监管指标验证了格里菲斯菌素的纯度和质量。已证明其对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和人类免疫缺陷病毒1型(HIV-1)有效,且与表达的GRFT的效力几乎相同。所提出的生产工艺高效,可轻松扩大规模并部署到世界上任何可能出现病毒病原体的地方。当前病毒变体的出现导致现有疫苗频繁更新,一线单克隆抗体疗法失效。像GRFT这样具有有效且广泛的病毒中和能力的蛋白质,为在疫情爆发源头迅速抑制病毒出现提供了极具吸引力的大流行缓解策略。