Systems and methods for virus propagation in cell cultures for vaccine manufacture
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Publication Number
US-9957485-B2
Publication Date
2018-05-01
Expiration Date
Abstract
The present invention provides a closed system to propagate virus-infected cells without the effect of shear force, while providing quicker access to nutrients than is available conventionally. This system design allows for a high density of infected cell growth to increase the virus yields and to maintain homogeneity of the contents of the main container. The system further provides a nuclease to degrade the cellular DNA prior for purification of the virus or viral components. As the system is designed for maximum containment at low risk, the live virus can be a hazardous virus such as a Bio-safety Level 3 (BSL 3), BSL 4 or BSL5 virus.
Core Innovation
The invention describes a scalable, closed-loop system and methods for bulk virus propagation and vaccine manufacture. The system uses stacked incubation chambers with permeable cell-attachment matrices to support adherent-cell growth, with controlled media circulation and a virus-capture pathway. Replicated virus is recovered and purified, then inactivated in sequential jacketed tanks. The supplied partial content does not include the background section, so the problem identified there is not explicitly described in patent.
At a high level, the claimed methods culture virus-infected cells in the closed-loop system, selectively retain replicated virus on an affinity matrix, and collect and inactivate it. The claimed system combines stacked chambers, a media tank, a virus-capture loop, an inactivation vessel, and automated monitoring and adjustment of cell-culture-medium components and fluid flow. The description also identifies nuclease treatment for degrading cellular DNA and sequential jacketed tanks for inactivation.
Claims Coverage
The relevant claims include three independent claims: two methods for producing bulk quantities of inactivated virus and one closed system for that purpose, comprising three inventive features.
Closed-loop method using adherent cells
The claim elements describe a method using stacked incubation vessels with permeable mesh affinity matrix material to support adherent cells, closed-loop cell-culture media circulation, and a virus-capture column. The method further includes [procedural detail omitted for safety] and collection and inactivation of replicated virus.
Closed-loop method with selective virus capture
The claim elements describe a method using stacked incubation vessels, cell-culture media tanks, and a column containing permeable mesh affinity matrix material to selectively bind replicated virus. The method further includes [procedural detail omitted for safety] and inactivation of the eluted virus for vaccine manufacture.
Closed system for bulk inactivated virus production
The claim elements describe a system with stacked incubation chambers containing permeable mesh matrices, a media tank, a virus-capture loop, a virus-inactivation vessel, and automated control systems and software for monitoring and adjusting cell-culture-medium components and fluid flow.
Together, the three independent claims cover two closed-loop methods for culturing cells and recovering and inactivating replicated virus, and a system comprising cell-incubation chambers, media circulation, virus capture, inactivation, and automated control.
Stated Advantages
Closed processing is intended to improve containment of hazardous viruses.
The rabies-virus example yielded an average of three times more vaccine doses than conventional methods.
Documented Applications
Bulk virus propagation and manufacture of vaccines, including the described rabies-virus example.
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