shutterstock_533717317This field of vaccine research, development and manufacture of viral therapeutics has not received the attention it has warranted in the past, presumably as higher returns from other therapeutic areas have taken priority, however, this is changing. In this article, I will look at how analytical technologies are, and can be, used for the design and manufacture of vaccines, but also into the research of potential therapeutics. For those also interested in genomic-based approaches to viral research, please visit our extensive information online here.

Research

Analytical technologies are frequently used in the research phase of both vaccine development and identification of therapeutics. Liquid Chromatography Mass Spectrometry (LC-MS) is commonly employed to characterise the virus, determine its components and, with the aid of cyro-electron microscopy, the viral structure as demonstrated in this recent publication. Another use of LC-MS is to determine the host cell response to viral infection to identify possible therapeutic targets. Such an approach has recently been used in this article. Here they infected cells with SARS-CoV-2 and used LC-MS, specifically the Thermo Scientific™ Q Exactive™ HF Hybrid Quadrupole Orbitrap™ Mass Spectrometer, to measure changes in the host cell proteome in response to the virus. They then tested drugs targeted at the identified pathways and found a number that could prevent viral replication.

Development

In the development phase, a wider range of chromatographic techniques are typically used. At this stage, likely therapeutic or vaccine candidates are identified and are assessed for efficacy. The therapeutic could be either a small molecule or large molecular drug, such as an antibody-based therapeutic, and in most cases would function by preventing virus entry into the host cell or disrupting its replication in some way. A vaccine is a biologic that is used to promote antibody production against a viral antigen to again prevent virus entry or replication. The vaccine is typically a disabled or modified form of the virus or a specific viral antigen that is given to the recipient who then ideally produces antibodies against those viral antigens and can then mount an effective immune response when exposed to the actual virus.

With both a vaccine and therapeutic, analytical technologies used to assess whether the right product has been produced for the development work, an estimation of yield and the presence of any impurities or contaminants. Again, LC-MS is likely to be used initially for discovery and identification, however, methods are then switched to liquid chromatography where possible for more routine analysis. Large molecule therapeutics, such as antibodies, do require a great deal of characterisation using a variety of liquid and ion chromatography and LC-MS applications and different column chemistries. For more information on the wide range of biotherapeutic characterisation techniques, please visit our learning centre. Finally, at this stage, the binding kinetics of the therapeutic are also assessed using technologies such as Surface Plasmon Resonance (SPR).

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Manufacture

At this stage, the final product has been developed and is now produced, formulated and packaged. Post-production, the product must go through extensive quality control to ensure efficacy and safety; is the product what we think it is, does it perform as expected, and is it free from impurities. This is considered a routine application so analytical techniques are required to be robust, simple to perform and running continuously to give the required throughput.

In these environments you typically encounter HPLC (High Performance Liquid Chromatography) being used for this QA/QC work; UHPLC (Ultra High Performance Liquid Chromatography)  is more commonly seen in the research and development stages. The HPLC will commonly use UV detection, or potentially single quadrupole mass spectrometry, to keep things simple. However, especially with vaccines and large molecule therapeutics, the added complexity eluded to earlier will require greater characterisation in QA/QC and will require LC-MS as well as standalone HPLC for full characterisation. The final step in the process is commonly referred to as formulation and fill. This is when the final product is mixed and prepared for use and then placed in its packaging for shipment and storage until use.

In summary, at each stage of the vaccine and therapeutic production workflow, there is a requirement for analytical technologies. The burden falls mainly to (U)HPLC and LC-MS, but even here, there are many different choices to make as to the appropriate HPLC instrumentation, chemistries and mass spectrometry system. When coupled with other approaches such as genomics, then you have a powerful suite of tools for fast and effective vaccine and therapeutics research and development.

Additional Information

  • To learn more about how Thermo Scientific™ Chromeleon™ Chromatography Data System (CDS) Software can be used for efficient and compliant vaccine and therapeutic research, development and production, please click here.
  • Discover more about biopharmaceutical analytical testing in the learning centre.