by Nelson Landrau, CEO/Founder, Landrau Scientific; Malcolm G. Pluskal, PhD.
This article was published by the North Central Massachusetts Chamber of Commerce in their Guest Columnist series.
Massachusetts has encouraged and supported Biopharmaceutical R&D and large-scale Biologics manufacturing throughout the last 30+ years and has become one of the world leaders in development of new technology platforms. Influenza, SARS, and the recent COVID-19 pandemic have increased the demand for novel vaccine production technologies to bring these vaccines to market quickly and in large quantities.
This demand has stimulated development of new mRNA-based vaccines by local companies in the Boston area. These new oligonucleotide-based vaccines offer great flexibility with respect to production and applications. This scientific approach will enable any protein to be encoded and expressed by an in vitro transcribed mRNA, in principle enabling the development of wide range of prophylactic and therapeutic vaccines to fight a broad range of diseases. To illustrate this diversity, this technology platform is being applied to fight diseases such as viral infections, cancer, and protein replacement therapy. During the production of this novel therapy only the mRNA sequence of the therapeutic target molecule is optimized. This enables diverse products to be manufactured using the same established production process, saving time and reducing cost as compared with other vaccine platforms.
Although mRNA therapy is diverse and can create new vaccines in relatively a short time period (as compared to other vaccine technology approaches), new manufacturing challenges have arisen to produce the large quantities of these novel vaccines to fight outbreaks such as COVID-19. As we react to this pandemic with this new class of vaccines based on mRNA and large molecule biologics such as monoclonal antibodies, future large-scale purification workflows will be challenged to meet production goals, regulatory requirements, and cost. Large scale production, packaging, and formulation to facilitate long term storage and deployment of these new vaccines will be key to their success. For example, mRNA-based vaccines are being formulated in charged liposomes to enhance their intra-muscular uptake and delivery to the body’s immune system, leading to in vivo production of therapeutic and viral neutralizing autoantibodies.
To meet some of these vaccine production demands several new purification technologies are under development in Leominster MA, to accelerate bringing these COVID-19 vaccines to market:
- Immunoaffinity resins for harvesting recombinant vaccine candidates from cell culture. This approach, taken by the University of Queensland for their “clamp” viral antigen, was first evaluated on a new orientated immobilization affinity bioprocess optimized resin developed by LANSI. This new resin offers high antibody binding capacity while preserving full antibody-antigen binding efficiency.
- mRNA vaccine candidates generated by in vitro transcription are being purified on oligo dT affinity resins targeting Poly A+ sequences on the 3’ end of the mRNA molecule. Existing first generation R&D oligo-dT affinity resins were based on cellulose beads not fully optimized for large-scale bioprocess applications. A new cellulose-based Oligo dT resin is under development at LANSI in collaboration with the Oligo Factory (Holliston, MA) based on resin beads that have been optimized for large scale bioprocess applications. Formulation of these novel vaccine candidates to confer stability and enhanced immunogenicity and delivery are in development at LANSI to support bringing these new vaccine molecules to market.
If your company has an mRNA or expressed protein viral antigen that you are looking for assistance in scale-up, purification, or formulation, please feel free to reach out to us for a complimentary confidential consultation at 978-537-2890 or write to us at info@landrauscienific.com. We have many years of experience in these fields and we are available to help you with your technical and product development needs.