The genetic material of nucleic acid vaccines can be DNA or mRNA, which is also encoded to produce targeted antigens in situ. A variety of vectors can be used to deliver genetic material to target tissues, including lipid nanoparticles (LNP), viral vectors, and plasmid DNA, or techniques such as electroporation can be used to enhance uptake. Alfa Chemistry provides customers with complete solutions to support their vaccine development process.
This new type of vaccine is chemically synthesized and encoded to directly produce specific disease antigens, which can be rapidly developed and scaled so that clinical materials can be used for trials and commercialization. They are also expected to prevent and treat various cancers by targeting tumor-associated antigens. Compared with more complex biological processes, the synthetic nature of such vaccines simplifies manufacturing challenges and is therefore generally considered to have strong and predictable safety. Despite these obvious advantages, there are still challenges related to the stabilization and delivery of genetic material to target cells and may bring special challenges in the production of the entire drug substance and the final formulation and filling process.
Fig.1 Innate immune sensing of mRNA vaccines. (Pardi N, et al. 2018)
Specifically, the use of lipid nanoparticles (LNP) as a delivery mechanism is being studied, but it is well known that these complex formulations may be affected by the low throughput of certain sterile-grade filters, and if not carefully filtered, The risk of bacterial infiltration increases selection and verification.
Ultrafiltration membranes used in the diafiltration and product concentration stages can be used for size-based purification.
Anion exchange membrane chromatography can be used for endotoxin control and change-based pollutant removal.
Complex formulations will bring unique filtration challenges, requiring careful selection of filters to maintain high yields. High-throughput capsules reduce product losses related to filter size and maintain high yields.
Keeping the manufacturing process clean is a core element of cGMP-compliant manufacturing. The use of single-use systems can range from collecting and transferring process components in biological treatment bags to complete integrated single-use manufacturing processes. This supports closed manufacturing processes and facilitates multi-product manufacturing to provide cost-effective, responsive, and agile processes.
DNA Vaccine - Plasmid Vector / Viral Vector
Vaccines that use plasmid DNA to transfect cells will cause one or more antigens associated with the target pathogen or cancer cell to be expressed in the cell. Although plasmids may encode different changes, these changes are similar to some stages in the production of viral vectors for gene therapy applications. The scale will vary according to the target disease, but the production process is basically the same.
Viral vector DNA vaccines use harmless viruses, such as poxvirus and adeno-associated virus (AAV), to deliver carefully designed genetic instructions to target tissues. These sequences are encoded to cause these tissues to produce the desired antigen, which then stimulates the immune system to produce antibodies. These processes share and utilize the same technologies like gene therapy applications, especially industrial-scale solutions that support adherent and suspension cell cultures used to propagate these viruses. Combined with the platform purification process, these vaccines can be rapidly developed and industrialized.
From media preparation to cell culture and purification, the use of disposable systems and bioreactors, coupled with sterile connectors and disconnectors, helps to maintain safety at all stages of the vaccine production process, final formulation, and filling.
- Pardi N, et al. (2018). "mRNA Vaccines - A New Era in Vaccinology." Nature Reviews Drug Discovery. 17: 261-279.