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Related Concept Videos

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Vaccine Production

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Vaccine production involves a sequence of upstream and downstream processes to generate a safe and effective immunological product. It begins with cultivating microorganisms, such as viruses or bacteria, to obtain antigenic material. For viral vaccines, mammalian host cells are grown in bioreactors and subsequently infected with the target virus. The virus replicates within the host cells, which are lysed to release viral particles. This lysate is then clarified through filtration or...
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Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
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Bioreactors are engineered vessels designed to cultivate microorganisms under controlled conditions for industrial bioprocessing. They maintain sterility and allow precise regulation of pH, temperature, oxygen, and nutrient levels to optimize microbial growth and metabolite production. Bioreactors range from small laboratory units of 1 liter to industrial systems holding up to 500,000 liters, though only about 75% of their volume is actively used for fermentation. The remaining headspace...
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Growth media provide essential nutrients that support cell growth and metabolism, thereby enhancing the yield of valuable products such as enzymes, antibiotics, and biomass. Designing an effective growth medium involves balancing all components to prevent nutrient limitations or toxic excesses, both of which can impair growth and reduce product yields.Composition of a Typical Growth MediumA typical growth medium contains carbon and nitrogen sources, salts, vitamins, trace elements, and...
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A continuous viral vaccine biomanufacturing platform utilizing multiple bioreactor configurations.

Justin Sargunas1, Bradley Priem1, Dylan Carman1

  • 1Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore, Maryland, 21218, USA.

Journal of Biological Engineering
|April 24, 2026
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Summary

This study introduces a continuous biomanufacturing platform using Sf9/recombinant baculovirus (rBV) for virus-like particle (VLP) production. The novel reactor system achieved stable cell growth and sustained recombinant protein expression for scalable bioprocessing.

Keywords:
Continuous biomanufacturingDigital twinPlug flow reactor (PFR)Sf9 insect cellsViral vaccinesVirus-like particle (VLP)

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Area of Science:

  • Biotechnology and Biomanufacturing
  • Cell Culture and Bioreactor Engineering
  • Molecular and Cellular Biology

Background:

  • Continuous biomanufacturing is crucial for meeting demands for smaller bioreactors, reduced costs, and consistent product quality.
  • The Sf9/recombinant baculovirus (rBV) system is a promising platform for producing virus-like particles (VLPs) for vaccines and gene therapies.
  • Existing biomanufacturing processes often face challenges with scalability and product heterogeneity.

Purpose of the Study:

  • To develop and validate a continuous biomanufacturing platform integrating multiple bioreactor types for rBV-based VLP production.
  • To assess the performance of a novel plug flow reactor (PFR) for infection within a continuous Sf9 cell culture system.
  • To demonstrate the potential for in silico modeling and quantitative frameworks in designing and optimizing continuous bioprocesses.

Main Methods:

  • Integration of a growth continuous stirred-tank reactor (gCSTR), a plug flow reactor (PFR), and a production continuous stirred-tank reactor (pCSTR).
  • Utilized Péclet number-fit tracer studies to confirm plug flow characteristics in the PFR.
  • Employed Western blotting and electron microscopy (EM) for VLP characterization and digital twin mechanistic models for process prediction.

Main Results:

  • Achieved a steady state of 5×10^6 cells/mL with >90% viability in the gCSTR.
  • Confirmed near-ideal plug flow in the PFR with a 10-hour residence time and progressive infection.
  • Demonstrated sustained recombinant protein production in the pCSTR over a 5-day continuous run, with successful VLP detection (~100 nm).

Conclusions:

  • The integrated multi-stage reactor system provides a scalable and continuous platform for rBV-based production, suitable for cell host- and product-agnostic applications.
  • Digital twin models accurately predicted cell growth and death, highlighting their utility for in silico process design and optimization.
  • This work lays the foundation for a true end-to-end continuous biomanufacturing platform for diverse therapeutic modalities.