Owing to their suitability for rapid pandemic response, leading candidates for SARS-CoV-2 vaccines, such as those from Moderna and BioNTech/Pfizer, are based on mRNA lipid nanoparticles (LNP). The genomic vaccine toolkit discussed below provides essential lipid nanoparticle formulation technologies and a manufacturing framework that accelerates drug candidates for vaccine development across indications from discovery to the clinic. The end-to-end solutions aim to support the development of RNA vaccines that are transforming a wide range of therapeutic fields including immunology.
Developing an RNA vaccine: a framework
Cytiva's genomic medicine development framework outlines a clear pathway for developing RNA vaccines, from antigen selection to scalable manufacturing processes. Each stage in the framework is supported by our genomic medicine toolkit which accelerates different phases of vaccine production.
Fig 1. Genomic medicine toolkit
1. Antigen selection: engineering for potency and safety
An effective vaccine development starts with proper antigen design. RNA vaccines facilitate the rational engineering of antigens. For example, mutations can stabilize the pre-fusion form of the coronavirus spike protein, enhancing vaccine effectiveness. Researchers from Moderna and Washington University in St. Louis engineered a Zika antigen to limit cross-reactivity with the dengue virus, making the vaccine safer (1). Our NanoAssemblr™ platform technologies are modular, allowing encapsulation, delivery, and manufacturing of nearly any encoded antigen, including large sequences over 10 kb.
Fig 2. LNP size is unaffected by RNA payload size.
Fig 3. Encapsulation efficiency (EE) unaffected by RNA payload size
2. Vector selection: self-amplifying RNA (saRNA) as a potent tool
saRNA vectors encode the antigen sequence along with RNA replication machinery. saRNA requires 10 to 100-fold lower doses than base-modified mRNA, significantly reducing the manufacturing burden (2). Projections suggest that enzymatic synthesis could yield 5 million human doses per liter, meeting the presentation and accessibility (manufacturing) requirements for widespread vaccine distribution. saRNA closely mimics natural infection without the risk of illness and possesses adjuvant properties, stimulating potent immune responses for durable protection.
Fig 4. saRNA encodes non-structural proteins 1-4 (nsP1 - nsP4) that are responsible for making more copies of the saRNA. Thus, more copies of the protein antigen are made per molecule of the RNA drug substance dosed.
3. Delivery and formulation technology: the role of lipid nanoparticles
LNP formulations are currently used in all RNA vaccines providing a desirable alternative to viral delivery. We offer a lipid portfolio that offers over a hundred ionizable lipids developed to optimize delivery efficacy and pharmacokinetic profiles suitable for intramuscular vaccination, making vaccine administration practical. Our LNP technology and GenVoy-ILM™ delivery platforms enable vaccine development without complications related to a packaging cell line, contamination with a replication-competent virus, and anti-vector immunity.
4. Scalable manufacturing process: from lab to commercial production
The NanoAssemblr™ technology allows LNP formulations to be prepared on demand in seconds. Non-turbulent microfluidic mixing provides exceptional control over the microenvironment of LNP formation, which influences physicochemical properties and biological activity. The NanoAssemblr™ family of instruments for lab scale to clinical scale share the same NxGen™ microfluidic architecture, therefore processes can be rapidly and easily scaled from discovery to commercial production.
RNA vaccines hold immense potential for democratizing access to life-saving vaccines, however, regulatory approval is a critical step in the commercialization of any vaccine, and the regulatory landscape for RNA vaccines is evolving. For mRNA and saRNA vaccines, demonstrating safety and efficacy in clinical trials remains the primary focus. Our LNP platform technology is designed to help drug developers navigate these regulatory hurdles by providing reproducible and scalable manufacturing technology that meets regulatory standards.
RNA vaccines can be rapidly produced and distributed even in resource-limited settings with our platforms making the manufacturing process more efficient and scalable. With our comprehensive genomic medicine toolkit for vaccine development, we aim to accelerate the development of RNA-based vaccines, including mRNA and saRNA candidates. Our end-to-end solutions from antigen design to manufacturing can enable faster and more efficient development of vaccines for diseases and future pandemics.
- Richner JM, Himansu S, Dowd KA, et al. Modified mRNA Vaccines Protect against Zika Virus Infection [published correction appears in Cell. 2017 Mar 23;169(1):176. doi: 10.1016/j.cell.2017.03.016]. Cell. 2017;168(6):1114-1125.e10. doi:10.1016/j.cell.2017.02.017
- Vogel AB, Lambert L, Kinnear E, et al. Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses. Mol Ther. 2018;26(2):446-455. doi:10.1016/j.ymthe.2017.11.017