通过接触式流深过产生基于复合囊泡性口腔炎病毒的载体
Sven Göbel1, Lars Pelz1, Cristina A T Silva2
1Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany.
Applied microbiology and biotechnology
|February 27, 2024
概括
一种新的触流深度过 (TFDF) perfusion 系统显著提高了病毒载体的产生. 这种封闭的系统可以持续收集和澄清病毒,实现更高的产量和加强疫苗和病毒治疗药物的生产.
科学领域:
- 生物技术和生物加工
- 病毒学和病毒载体生产
- 细胞培养和生物反应器技术
背景情况:
- 基于细胞培养的生产基于载体的疫苗和病毒治疗药物正在变得越来越重要.
- 现有的方法需要优化,以实现高效和持续的病毒收集和澄清.
- 基于复合囊泡性口腔炎病毒 (rVSV) 的载体对治疗应用具有前景.
研究的目的:
- 评估一个集成的封闭一次性输液系统,用于持续生产病毒载体.
- 评估触流深度过 (TFDF) 对于细胞保留,病毒收集和澄清的有效性.
- 为了比较TFDF perfusion系统的性能与优化的批量工艺.
主要方法:
- 在悬浮BHK-21和HEK293-SF细胞中使用两种基于rVSV的结构进行概念验证研究.
- 实施修改的交替接触流 (mATF) 装置和接触流深度过 (TFDF) 系统,用于细胞保留.
- 灌种植,持续收获和澄清,然后进行传染性病毒标位量化.
主要成果:
- 该TFDF系统实现了高可活细胞度 (VCC),高达20.6×10^6细胞/毫升.
- 通过使用TFDF系统,成功地证明了持续的载体采集和澄清.
- 与批量工艺相比,TFDF输液系统的传染性病毒标位高达11倍,时空产量增加了460%.
结论:
- TFDF perfusion 系统对于强化病毒载体生产是有效的,使得持续的收集和澄清成为可能.
- 这种综合系统在生产疫苗和病毒治疗药物的传统批量方法上提供了显著的优势.
- 该TFDF perfusion系统显示了建立强化和高效的病毒载体制造工艺的巨大潜力.
相关概念视频
What are Viruses?
Overview
Lytic Cycle of Bacteriophages
Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the lytic replication...
Viral Recombination
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
Infection
When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
Introduction to Virus
Viruses are unique biological entities that blur the boundary between living and non-living systems. Although they lack cellular structure and metabolic processes, they can exhibit characteristics of life when infecting a host. Their defining feature is a nucleic acid core, composed of either DNA or RNA, encapsulated within a protein coat called a capsid. This simple structure allows them to invade host cells and use their machinery for replication efficiently.Viral Structure and...
Poliomyelitis
Poliomyelitis is caused by poliovirus, a small, non-enveloped, positive-sense RNA virus of the Picornaviridae family and Enterovirus genus. Transmission occurs primarily via the fecal-oral route, often through ingestion of contaminated water or food. The virus initially replicates in the oropharynx and intestinal mucosa, particularly in lymphoid tissues such as the tonsils, Peyer’s patches, and regional lymph nodes. Primary viremia follows, allowing dissemination throughout the body.In most...


