用烟花椰菜生产的抗呼吸道合胞病毒单克隆抗体的中和活性。

IF 4.1 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Human Vaccines & Immunotherapeutics Pub Date : 2024-12-31 Epub Date: 2024-03-20 DOI:10.1080/21645515.2024.2327142
Nuttapat Pisuttinusart, Kaewta Rattanapisit, Chanya Srisaowakarn, Arunee Thitithanyanont, Richard Strasser, Balamurugan Shanmugaraj, Waranyoo Phoolcharoen
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引用次数: 0

摘要

呼吸道合胞病毒(RSV)是一种传染性极强的病毒,会影响许多易感人群的肺部和呼吸道。它是导致下呼吸道感染和临床并发症的主要原因,尤其是在婴儿和老年人中。它可发展成肺炎和支气管炎等严重并发症。目前,RSV 疫苗或免疫预防剂的研发仍处于高度活跃期,是全球健康领域的优先事项。目前,葛兰素史克的 Arexvy™ 疫苗已被批准用于预防老年人(大于 60 岁)的下呼吸道疾病。Palivizumab 和目前的 nirsevimab 是获批用于高危患者 RSV 预防的单克隆抗体 (mAbs)。目前正在进行多项研究,以开发出更多用于预防新生儿和其他易感人群 RSV 感染的治疗性抗体。最近,又发现了一些抗体,并显示出作为帕利珠单抗和 nirsevimab 治疗替代品的更大开发潜力。植物表达平台已被证明能成功生产包括抗体在内的重组蛋白,为哺乳动物表达平台提供了一种潜在的具有成本效益的替代方案。因此,本研究尝试利用植物表达平台生产两种抗 RSV 融合(F)mAbs 5C4 和 CR9501。这两种抗体的重链和轻链序列都是用geminiviral载体在烟草植物中瞬时表达的,然后用单步蛋白A亲和柱色谱法纯化。这两种植物生产的 mAbs 都显示出与 RSV 融合蛋白的特异性结合,并在体外显示出有效的病毒中和活性。这些初步研究结果表明,植物生产的抗 RSV mAbs 能够在体外中和 RSV。
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Neutralizing activity of anti-respiratory syncytial virus monoclonal antibody produced in Nicotiana benthamiana.

Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK's Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in Nicotiana benthamiana plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity in vitro. These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV in vitro.

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来源期刊
Human Vaccines & Immunotherapeutics
Human Vaccines & Immunotherapeutics BIOTECHNOLOGY & APPLIED MICROBIOLOGY-IMMUNOLOGY
CiteScore
7.90
自引率
8.30%
发文量
489
审稿时长
3-6 weeks
期刊介绍: (formerly Human Vaccines; issn 1554-8619) Vaccine research and development is extending its reach beyond the prevention of bacterial or viral diseases. There are experimental vaccines for immunotherapeutic purposes and for applications outside of infectious diseases, in diverse fields such as cancer, autoimmunity, allergy, Alzheimer’s and addiction. Many of these vaccines and immunotherapeutics should become available in the next two decades, with consequent benefit for human health. Continued advancement in this field will benefit from a forum that can (A) help to promote interest by keeping investigators updated, and (B) enable an exchange of ideas regarding the latest progress in the many topics pertaining to vaccines and immunotherapeutics. Human Vaccines & Immunotherapeutics provides such a forum. It is published monthly in a format that is accessible to a wide international audience in the academic, industrial and public sectors.
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