An article in Nature Biotechnology in April 2023 explores the possibility presented through an automated process for printing microneedle patch (MNP) mRNA vaccines for COVID-19 in a standalone device. The hope that this format could “enhance vaccine access in low-resource communities” was supported by the research, suggesting that “efficacious, microgram-scale doses of mRNA encapsulated in lipid nanoparticles” can be delivered through a single patch.
The question of access
The paper begins by exploring the vulnerability of unvaccinated communities in low- and middle-income countries, which are at risk of repeated outbreaks of COVID-19 and other infectious diseases. These risks “increase mortality, promote the emergence of more dangerous variants and negatively impact the economy”.
Despite mass vaccination attempts, efforts in these communities have been “hampered” by issues like “inadequate cold-chain-compatible storage and transport infrastructure” as well as an “insufficient number of healthcare personnel”. The authors identify a “potential solution” in distributed, local systems for manufacturing suitable vaccines, and explore the possibility of MNPs as a “promising vaccine format”.
The perks and challenges of MNPs
MNPs (microneedle patches) can be self-applied, are less painful than intramuscular injection, create no sharps waste, and can be formulated to be shelf stable for months. Furthermore, they have been used with several types of vaccines. For COVID-19, lipid nanoparticle (LNP)-encapsulated mRNA vaccines have proven “highly effective in preventing severe disease”. However, “intradermal delivery of an mRNA vaccine in an LNP vehicle using an MNP with long-term thermostability” has not been previously reported.
Although there are clear benefits to the development of MNPs, their manufacturing introduces “new challenges” in “fabrication, loading, and scalability”.
“For accurate dosing and adequate skin penetration, microneedles must be sharp and consistent in size from batch to batch.”
Furthermore, they are limited by the “small volume available for vaccine loading” and are typically handmade with “labour-intensive, manual, and imprecise steps”. These issues make “consistent, automated manufacturing” a challenge.
In the study the authors present a microneedle vaccine printer (MVP). This fabricates dissolvable MNPs loaded with LNP-encapsulated mRNA vaccines or similar. The approach does have its own challenges. Microneedle formation must produce “sharp, accurate, and micron-scale” microneedles. Mould filling “must be driven by a repeatable process that minimises waste, reduces moving parts, requires no user interaction, and integrates into an automatable machine-driven workflow”.
“The process used in the device is based on vacuum application, compatible with a wide range of MNP designs, and optimised to minimise vaccine waste.”
This technique drives viscous vaccine inks into moulds, “based on air’s permeability and solubility in polydimethylsiloxane (PDMS)”. To reduce waste and drying time, the minimum possible volume of vaccine ink was dispensed. To reduce use interaction and the need for on-site training, several processes were automated with programmable components. The first-generation printer is capable of manufacturing 100 patches in 48 hours. However, this can be increased by altering the size and complexity of the dispensing stage and drying area.
What does the approach show?
Although the “magnitudes” of humoral responses were similar, the researchers identified “interesting differences” between intramuscular administration and intradermal delivery. The results suggest that MNPs may be sensitive to ionisable lipid composition, and that humoral responses develop faster intramuscularly.
“MNPs containing mRNA-LNPs offer new opportunities to streamline vaccine administration and improve vaccine efficacy.”
Furthermore, room-temperature-stable vaccines would “greatly facilitate deployment in the developing world” and allow for vaccines to be “cost-efficiently stockpiled” in anticipation of future outbreaks.