NanoMedU
Learn more about Early Pre-clinical Development Level 1: RNA Vaccines. A focused virtual classroom and hands-on training to kick-start RNA-LNP vaccine development
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Vaccines
Owing to their suitability for rapid pandemic response, the leading candidates for SARS-CoV-2 vaccines from Moderna and BioNTech/Pfizer are based on mRNA lipid nanoparticles.
Precision NanoSystems' Genetic Vaccine Toolkit provides essential technologies to facilitate development of mRNA vaccines that are revolutionizing the field.
Vaccine Toolkit
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Genetic Payload Platform -
GenVoy™ Delivery Platform -
NanoAssemblr® Manufacturing Platform
PNI Vaccine Technology
PNI is developing a SARS-CoV-2 vaccine that leverages our self-amplifying RNA technology, our proprietary lipid library for delivery, and our NanoAssemblr™ Platform for manufacturing. Recently, collaborators at Imperial College London tested some of our prototype formulations and found they mediated a potent response in a mouse model for influenza.
Watch the webinar presented by Anna Blakney, Imperial College London
How to Develop an RNA Vaccine
PNI’s framework for genetic medicine development provides guidance on the key stages and milestones for developing genetic medicines. Below is an example of how the parts of the Genetic Medicine Toolkit fit within the framework to accelerate different stages of vaccine development.
PNI’s Genetic Medicine Development Framework and Toolkit for RNA Vaccines
During drug development, selection of different materials, technologies and formulations are guided by the target product profile (TPP). While the specifics of the TPP for a given vaccine depends on the target, and the market landscape, some characteristics can be generalized:
Vaccine Characteristics
General Requirements
Durability of Protection
Confers protection for at least 6 months.
Route of Administration
Any route of administration is acceptable, if vaccine is safe and effective. Intramuscular is common.
Product Stability & Storage
Outbreak: shelf life of at least 6-12 months as low as -60℃ to -70℃, demonstration of at least 2 week stability at 2-8℃.
LT: storage at -20℃ or higher.
Presentation
Multi- or mono-dose presentations are acceptable.
Maximum parenteral dose volume: 1mL.
Accessibility
Outbreak: Capibility to rapidly scale-up production at cost/dose that allows broad use, including in LMIC.
LT: Availibility of sufficient dose at cost/dose that allows broad use, including LMIC.
Abbreviations: LT = Long Term; LMIC = Low- and Middle-Income Countries
1. Antigen Selection
An effective vaccine starts with proper antigen design. RNA vaccines facilitate rational engineering of antigens. For example, mutations can be engineered into the antigen code to stabilize the pre-fusion form of corona virus spike protein to improve vaccine effectiveness. In another example, researchers from Moderna and Washington University in St. Louis, engineered a Zika antigen that limited cross-reactivity with dengue virus [1] thus making the vaccine safer. PNI’s technologies are modular, allowing encapsulation, delivery, and manufacturing of nearly any encoded antigen including large sequences over 10 kb.
LNP size unaffected by RNA payload size
Encapsulation efficiency unaffected by RNA payload size
2. Vector Selection
Self-amplifying RNA (saRNA) are vectors that encode the antigen sequence along with RNA replication machinery. Self-amplifying RNA requires 10- to 100-fold lower doses than base modified mRNA [2], thus significantly reducing the manufacturing burden. Projections suggest 5 million human doses can be produced per litre via enzymatic synthesis, which is ideal for meeting the presentation and accessibility (manufacturing) requirements.
saRNA also closely mimics a natural infection without the risk of illness and has adjuvanting properties, meaning saRNA stimulates potent immune responses to confer durable protection.
Self-amplifying mRNA
Non-amplifying mRNA
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
PNI offers a lipid library for vaccine applications that are suitable for intramuscular vaccination, making them more practical to administer than intravenous injections. PNI’s lipid nanoparticle (LNP) technology enables a synthetic vaccine without the complications of a packaging cell line, contamination with replication-competent virus and anti-vector immunity. LNP formulations are being used for all RNA vaccines currently being developed for COVID-19 because they offer a desirable alternative to viral delivery.
PNI’s LNP Delivery Technology
4. Manufacturing
PNI’s NanoAssemblr® technology, allows LNP formulations to be prepared on demand in seconds. Non-turbulent microfluidic mixing affords exceptional control over the microenvironment of LNP formation that ultimately influences physico-chemical properties and consequently biological activity. Because the Spark, Ignite, Blaze and GMP systems share the same NxGen microfluidic architecture, processes can be rapidly and easily scaled from discovery to commercial production.
PNI’s NanoAssemblr™ Technology
The NxGen mixer enables the reproducible scale-up of mRNA-LNP and other complex nanomedicine formulations
Test batches of up to 12 L/h produced with a single NxGen mixer
Particle characteristics (size and PDI) are consistent
Biological activity maintained
End-to-end RNA Vaccine Development Solutions
We are committed to supporting our clients’ RNA vaccine programs with a full stack of technologies and solutions with leading experience to accelerate the design, development and manufacturing of promising vaccines.
Genetic Medicine Toolkit
Essential technologies to facilitate development of mRNA vaccines
References
1. Richner, J. M., Himansu, S., Dowd, K. A., et al. (2017). Modified mRNA Vaccines Protect against Zika Virus Infection. Cell, 168(6), 1114-1125.e10. https://doi.org/10.1016/j.cell.2017.02.017
2. Vogel, A. B., Lambert, L., Kinnear, et al. (2018). Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses. Molecular Therapy, 26(2), 446–455. https://doi.org/10.1016/j.ymthe.2017.11.017
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