Recombinant Protein Vaccine Process

Recombinant protein vaccines have an established track record in the industry, starting in the mid-1980s with the hepatitis B vaccine, now a routine vaccination around the world. These vaccines marked the first transition away from traditional manufacturing, overcoming many barriers in vaccine development and production. Unlike the purification of an antigen from an inactivated pathogen, recombinant production of antigens allows high expression levels and improves vaccine safety.


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What Are Recombinant Protein Vaccines?

Recombinant protein vaccines, also called recombinant subunit vaccines, are formulated using defined protein antigens that can be produced in heterologous expression systems. A great number of expression systems can be evaluated depending on the antigen to be produced: bacteria, yeasts, insect cells, mammalian cell lines or plants. The challenge of the industry today is supporting the scale-up of these various expression systems and developing downstream processes tailored to disease-specific antigens.

How It Can Serve the Industry, Including the Pandemic Response?

Recombinant protein vaccines revolutionized the vaccine industry years ago, enabling the development of vaccines to address unmet needs. Today, recombinant proteins represent a significant part of the vaccine pipeline, with promising candidates for a number of diseases, such as RSV and HIV, as well as a new generation of influenza vaccines. In the scope of the COVID-19 pandemic, over 30% of vaccine candidates rely on the recombinant protein vaccine process, most of them focusing on the virus’s spike protein. The advantage of using this proven strategy in a pandemic situation is the ability to produce a safe vaccine with a highly productive process that can be manufactured in existing facilities.

The Success of Virus-Like Particles.

Virus-like particles (VLPs) are multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome, potentially yielding better immune response at a lower dose when compared to the protein alone. VLPs are produced through the individual expression of viral structural proteins, which can then self-assemble into the virus-like structure. Enveloped VLPs assemble by budding out of the cells, while non-enveloped VLPs are assembled during the downstream process. A number of expression systems can be used: bacteria, yeasts, insect cells, plants or mammalian cell lines, depending on the VLP complexity. A successful example of VLP vaccine is the Human Papillomavirus produced in yeasts. 

The great variability of recombinant protein vaccines eliminates the possibility of a ready-to-use platform supporting all development steps, so strategic partners with innovative solutions are needed to enable the development of highly productive and safe recombinant protein vaccines.

 Recombinant Protein Vaccines

Cell Line Development

Upstream Processing (USP)

Downstream Processing (DSP)

Other Technologies

Advanced chemometric methods, such as Design of Experiments (DOE) and Multivariate Data Analysis (MVDA), give broad visibility into data, ultimately leading to greater process reliability and robustness in addition to cost savings.

Needs

Solutions

Quality by Design (QbD) relies on DoE to understand critical process parameters, which is dependent on implementing many experiments – a tool that can help design and plan experiments alleviates the burden.

Process Analytical Technologies generate a lot of data that is difficult to analyze, resulting in significant demand for a tool to evaluate historical data in order to identify correlations, conduct troubleshooting and gain process understanding.  

Most vaccine developers and manufacturers are not statisticians and rely on user-friendly interfaces and software.

The Umetrics® suite includes three user-friendly and intuitive software solutions designed for process developers and manufacturers to support data analytics through unique data visualization, extensive wizard functionality and customizable plots to maximize usability and versatility:

  • MODDE® is an advanced, high-quality DOE solution designed for ease of use. The benefit of DOE is to gain knowledge and estimate the best-operating conditions of a process or product, and with MODDE® the graphical interface and analytics support make it easy to interpret results with complete confidence  
  • SIMCA® Multivariate Data Analysis (MVDA) software is used for scale and batch-to-batch comparison investigations. SIMCA transforms data into visual information for easy interpretation, enabling decisions and actions to be taken rapidly and with confidence. SIMCA helps to analyze process variations, identify critical parameters and predict final product quality. An overview of the process status can be obtained in a few clicks  
  • SIMCA®-online is a highly efficient software for real-time multivariate statistical process monitoring and control. SIMCA® online provides a complete set of interactive and visual monitoring tools to production teams to ensure that batch and continuous operations run smoothly

These software solutions are fully integrated in most Sartorius systems and are available as stand-alone programs.

 

 The increasing development of single-use technologies with integrated single-use sensors has not only enabled real-time data gathering and analysis, it has resulted in process efficiencies, reduced risk of contamination, improved operator safety and overall titer improvements.

Needs

Solutions

Vaccine manufacturers want to better understand and control their processes, which are very complex and highly regulated, but to do so requires real-time measurement of critical process parameters to allow process monitoring, set-point control (feed control and bleed control), event time point predictions (harvest and infection) and timely identification of process deviations.

A range of PAT sensors would be required to effectively apply QbD principles and ensure consistency in product quality and quantity, quickly identifying and correcting process deviations to reduce the risk of lost batches.

The ability to integrate PAT into single-use systems would mitigate risk of spillages and contamination during sampling.

BioPAT® toolbox, an expending range of fully qualified single-use sensors, are integrated across the Sartorius portfolio making Sartorius the market leader for PAT

  • Available in process development and manufacturing technologies for full process understanding, monitoring and control
  • Data analysis is straightforward thanks to the full integration in the Sartorius products and technologies  
  • BioPAT® Viamass for inline monitoring of viable cell density and automated cell bleed control
  • BioPAT® Trace for online monitoring of glucose and lactate and automated feed control
  • BioPAT® Xgas for inline monitoring of CO2 and O2
  • BioPAT® Spectro platform for Raman spectroscopy integration in Ambr® and STR bioreactor systems for non-invasive, inline measurement of multiple analytes
  • BioPAT® Single-Use Sensors for accurate monitoring of critical process parameters, including pH, conductivity, dissolved oxygen, flow rate and pressure. These sensors are integrated throughout the Sartorius portfolio of Bioprocessing Systems, according to each unit operation’s specific needs

 

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