Electrospun mucoadhesive matrices for polymersome-mediated mRNA vaccine delivery

Immunisation is of utmost importance for global health, as it plays a crucial role in preventing millions of deaths worldwide each year. It has proven highly effective in the prevention and, in some cases, near-eradication of life-threatening diseases like polio, measles, and whooping cough. The emergence of the coronavirus pandemic accelerated the development of vaccines, with messenger RNA (mRNA)-based vaccines pioneered by companies such as Moderna and BioNTech leading the way in combating COVID-19. This breakthrough in vaccine development has opened up new possibilities for preventing the spread of other diseases that were previously very difficult to address. However, mRNA vaccines come with specific challenges. Current mRNA vaccines necessitate strict cold storage conditions, which pose difficulties in terms of storage, transportation, and quality control. They are administered by injection that requires access to sterilised equipment as well as trained healthcare professionals such as nurses and doctors. Many of these requirements are not available in parts of the world where vaccines are most needed. Furthermore, offering alternative methods of vaccine administration that do not involve injections would enable individuals with needle phobias to receive vaccinations.

To address these challenges, our goal is to transform vaccine delivery by developing an mRNA vaccine loaded within a patch that can be deployed safely to soft tissues in the mouth. This innovative technology involves enclosing the mRNA within tiny synthetic polymer capsules that provide protection and stability. These polymer capsules are delivered from microfibers that make up the mesh of the patch, and allow for storage at ambient temperature, simplifying transportation and storage logistics.

To administer the vaccine, the patch may be pressed against the surface of the inside of the cheek. Upon contact with saliva, the microfibers within the patch gel, facilitating its adhesion while simultaneously releasing the polymer capsules containing the mRNA. These polymer capsules then penetrate the cheek tissue, delivering the mRNA to immune cells residing within it. Once the immune cells uptake the mRNA, they become activated, triggering an immune response by generating T-cells and producing antibodies that protect against the targeted disease. In addition to transforming vaccine delivery, a further aim is to develop more efficient manufacturing methods for these vaccine-containing patches, ultimately reducing production costs. The creation of these patches would benefit numerous individuals. By providing a needle-free, self-administered vaccine option that can be stored at ambient temperature, our technology has the potential to improve vaccine accessibility, especially for underserved populations in remote regions. Furthermore, it offers a more convenient and accessible immunisation method for individuals who experience needle-phobia.

Immunisation is a cornerstone of global healthcare, preventing millions of deaths per year worldwide. The SARS CoV 2 pandemic catalysed rapid vaccine development, with messenger RNA (mRNA)-based vaccines at the forefront of strategies to combat COVID-19. This technology has created the opportunity to expand vaccine coverage to many other diseases not previously possible. However, mRNA vaccines are not problem-free. mRNA and their carrier, lipid nanoparticles (LNP), are heat labile and require strict cold-chain storage, causing logistical and quality control challenges. They are administered by injection requiring access to sterilised equipment and trained healthcare professionals. Many of these requirements are not available in parts of the world where vaccines are most needed. Moreover, availability of self-administered, needle-free delivery would also enable vaccination to people with needle-phobia. To resolve these problems, we aim to transform vaccine delivery by developing a mRNA vaccine-containing mucoadhesive matrix that will deliver mRNA directly to immune cells within the oral epithelium to initiate a protective immune response. To achieve this, target mRNA will be loaded into polymersome vesicles that permit greater drug-loading capacity, higher stability, enhanced drug retention, and controlled drug release compared to LNP. mRNA loaded-polymersomes will be incorporated into a mucoadhesive microfibre matrix that upon contact with the oral mucosa release polymersomes that then enter the oral epithelium where they are preferentially taken up by dendritic cells. Once inside, polymersomes disassemble, rupturing endosomes, releasing mRNA into the cytosol. Peptides derived from mRNA translation are displayed on the surface of antigen-presenting cells which then engage with T-cells, driving both cell- and antibody-mediated immunity. Simultaneously, continuous scalable production strategies will be developed for enhanced vaccine biomanufacturing of these matrices.