Tools for Vaccine Development and Production
The trend in vaccine manufacturing is towards increased capacity due to the development of vaccines for new applications such as cancer prevention. Revised recommendations for seasonal ﬂu prevention and the ever-present concern over a pandemic are also major drivers.
This means that fast method development and predictable scale-up to optimized cGMP-compliant manufacturing processes are required. Selecting the right strategy to efficiently generate large quantities of antigen with suitable vaccine properties (high immunogenicity/low pathogenicity) is a considerable challenge. Read on to find out how our tools and expertise can help you meet those requirements.
From Development to Manufacturing
A growing number of vaccines are based on well-defined materials, including those based on purified protein antigens of natural origin or produced by recombinant DNA technology, polysaccharides, oligosaccharide protein conjugates, and novel nucleic acid constructs.
These products raise challenges for identification, characterization, purification, and analysis. GE Healthcare has a comprehensive offering of tools and expertise for vaccine manufacturers and researchers throughout the vaccine development process, from target identification to batch release.
Learn more about our tools for efficient process development.
Fast Trak Bioprocess Development Services has extensive experience in biopharmaceutical manufacturing. Let us help you streamline your process development and transfer upstream and downstream processes to pilot or manufacturing scale.
The identification of suitable antigens as vaccine candidates depends on research that elucidates structural and functional interactions between pathogens and the host immune system.
Surface plasmon resonance (SPR) and Isothermal titration calorimetry (ITC) are orthogonal and complementary methods that advance vaccine research and design by providing accurate, information-rich characterization data about binding between viral epitopes and elicited antibodies. Binding properties, such as kinetics and thermodynamics, are important parameters in early research and structure-guided design of protein-based vaccines against viruses, parasites, and cancer.
Vaccine production has several stages. First, the antigen itself is generated. Viruses are grown either in primary cells (such as chicken eggs for the production of influenza vaccine), or in established cell lines. Bacteria, such as Haemophilus influenzae type b, may be grown in bioreactors. Alternatively, a recombinant protein derived from viruses or bacteria can be generated in a variety of expression systems such as in yeast, bacteria, or mammalian cells.
WAVE Bioreactor systems use a disposable Cellbag bioreactor that does not require cleaning or sterilization, making it particularly suitable for GMP-compliant production of therapeutic cells. Culture media can be supplemented with lectins or mitogenic agents to increase productivity or to activate cells for specific applications. Even anchorage-dependent cells can be expanded successfully by using Cytodex microcarriers.
GE Healthcare Life Sciences has decades of experience developing tools and methodologies to purify different types of vaccines—including viruses, plasmids, and proteins—using a range of filtration and chromatographic techniques.
As the majority of the approved vaccines are based on bacteria, viruses, or polysaccharides/conjugated polysaccharides, size-based separations play a prominent role in processing.
Depth or normal flow filtration (NFF) is generally the first membrane technique applied, used for clarification and/or bioburden reduction. This is usually followed by cross-flow filtration (CFF/TFF) using hollow-fiber cartridges for concentrating and washing feed streams. Sterile filtration at the end of the process assures final vaccine safety. In addition, depth filters are often used between chromatography steps to protect columns.
Chromatography offers several techniques for highly efficient purification of a range of biomolecules. Size-exclusion chromatography using Sepharose and Sephacryl gel filtration media for group separation has long been used in vaccine processing.
Today other chromatographic techniques such as affinity and ion exchange play an increasing role. GE Healthcare offers a number of chromatography media (resin) for vaccine purification, several based on the high-flow agarose base matrix such as Capto.
We also offer ready-to-use, disposable technologies for upstream and downstream processing of vaccines. The ReadyToProcess platform simplifies and speeds up bioprocessing by reducing time-consuming activities and increasing manufacturing agility. ReadyToProcess covers a range of products for cell culture and fermentation, filtration and purification, as well as fluid management and connectivity.
If you require a custom solution to suit your specific needs, GE Healthcare provides custom designed chromatography systems, columns, and media (resins).
Batch Release Testing
High quality analytical tools are required to measure the recovery, yield, and purity of viruses in vaccine process control and batch release. One problem in influenza vaccine development is that the analytical tools available to quantitate influenza virus are not satisfactory. The most commonly used method, single radial immunodiffusion (SRID), is labor intensive and is further limited by low sensitivity and high variability.
Surface plasmon resonance (SPR) biosensor technology used in GE Healthcare’s Biacore systems can be used for virus titration (for example, hemagglutinin (HA) quantitation for influenza virus) with higher sensitivity, less hands-on time, and higher precision than SRID and other commonly used methods such as ELISA. Biacore systems can also be used for accurate and sensitive quantitation of host cell protein (HCP) impurities during process development and batch release testing.
Characterization and Monitoring of Immune Responses
The successful development of a vaccine requires optimization of vaccine variants and immunization regimes, characterization of serum responses over extended time periods, and assessment of the biological efficacy of the generated antibodies. Label-free interaction analysis using Biacore systems offers a number of advantages in immune response studies, including the possibility to detect early antibody responses to vaccine candidates directly from serum samples.
Biacore systems provide data for multiple immune response characteristics such as specific binding levels, binding stability, isotype, and subclass determination. Together, this allows the optimization of immunization regimes by adjusting dosing schedules, adjuvant types, and concentration.
Cytokines are involved in all types of immune responses from inflammation and autoimmunity to antibody responses and T cell immunity. Biotrak Cytokine and Growth Factor ELISA Kits allow the convenient measurement of cytokine protein levels in serum, plasma, and cell culture samples.