No one likes getting a shot. Dissolvable skin patches are the way of the future for delivering vaccines. They are effective, safe and virtually painless. Why aren’t they a reality yet?
How do Dissolvable Microneedle Skin Patches Work?
Skin serves as our body's barrier to the outside world; regulating what gets in and what gets out. Researchers can capitalize on the skin's natural ability to respond to an invading pathogen. Dissolvable microneedles can deliver vaccines directly to the dermis and the immune cells that reside there, but the term “microneedle” is a little misleading.
A microneedle patch is about the size of a stamp. The cone like structure of the microneedle has a height of 450 µm, which is more than 50x smaller than 1 inch. Microneedles produced by Tinker laboratory at Boise State University in collaboration with the Idaho Microfabrication Laboratory. Microneedle image collected at 0.64x on a Zeiss Stemi 2000-C Stereo Microscope.
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Microneedles are really patches about the size of a stamp and are composed of about 100 microscopic cones. These cones are referred to as microneedles simply because they can penetrate the skin, but they are not painful like an intramuscular needle. The texture of a microneedle patch has been described as feeling like a cat’s tongue.
While there are many microneedle formulations being investigated, they are often composed of sugar and salt solutions. The skin naturally allows sugar and salt into the body. Any type of vaccine, whether a protein, mRNA covered in a lipid nanoparticle or other cellular component of a pathogen, can then be added to the sugar and salt solution and dried. Once the microneedles are applied to the skin, the moisture in a patient’s skin can dissolve the microneedles and absorb the vaccine components. The immune cells in the skin, called Antigen Presenting Cells (APCs), then recognize the foreign particles of the vaccine and activate B and T cells. Within a few weeks, these cells create the memory that is necessary to prevent future invasions of the pathogen. The memory cells will be systemic and can recognize pathogens throughout the body as well as pathogens entering through the skin or mucosal membranes.
Why are Dissolvable Skin Patches Better than Needles for Delivering Vaccines?
Microneedles Prevent Transmission as Well as Infection
Microneedles deliver vaccine to the skin, whereas intramuscular vaccines must travel through the skin, fat and into the muscle.
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Intramuscular vaccination uses a needle to deliver vaccines (e.g., pathogen genetic material or antigens) to a large muscle group, often of the upper arm. This type of vaccine delivery is effective at preventing an infection from taking hold and causing disease, but the pathogen must be inside the body for the immune system to recognize it. This is 1 reason you may still get infected with COVID-19 or the flu after being vaccinated.
Dissolvable microneedle patches, on the other hand, deliver the vaccine to the skin, triggering the immune response in the skin. The body then learns to search for this pathogen in our skin and mucosal membranes, as well as inside the body. For example pathogens that are spread through droplet transmission and enter through mucosal membranes will be recognized and neutralized before taking hold in the cells of the respiratory tract.
Importantly, since individuals can often spread a pathogen before they demonstrate symptoms, blocking the pathogen from entering the body by vaccinating through the skin, also prevents it from replicating to a spreadable level and effectively reduces transmission.
Unfortunately, the immune system does not always catch invading pathogens, even when it is primed to look for them. Vaccinating with a dissolvable microneedle patch allows for the skin and mucosal membranes to be on the lookout for invading pathogens, but if a pathogen gets past the skin and into the body, the host is still protected. Once the APCs in the skin recognize the foreign particles, the APCs travel to the lymph nodes and activate B and T cell for a systemic immune response. Dissolvable microneedle patches give the distinct advantage of activating both a local, skin level protection, as well as a system, whole body protection.
Microneedles Cause Fewer Side Effects Than Intramuscular Injections
The amount of time it takes to dissolve a microneedle patch is determined by the composition of the sugar solution. The microneedle patches can be designed to dissolve within minutes to hours, allowing for a slower release than an intramuscular injection, which hit the immune system with the entire dose of vaccine all at once and cause the injection site to often feel hot, swollen and sore. While this is a positive sign and means that the vaccine is being recognized by the immune system, it can be uncomfortable.
Additionally, localized immune responses from intramuscular injections can trigger systemic immune responses, which is why you can get a runny nose, sore throat or headache after vaccination. But delivering the vaccine slowly through a dissolvable patch elicits immune activation without a massive inflammatory response, meaning the dissolvable microneedle vaccine delivery allows for an effective immune response with fewer side effects. These properties (effectiveness and reduction in side effects) have been evaluated for a variety of vaccines delivered by microneedle patches.
Dissolvable Skin Patch Vaccines are Painless
The last major benefit of the dissolvable skin patch vaccination over the traditional intramuscular delivery is that there is no pain. According to the U.S. Centers for Disease Control and Prevention (CDC), one of the biggest barriers to vaccination is the fear of pain associated with needles. The most pain associated with dissolvable microneedles is the removal of the adhesive patch.
What is Needed to Make Dissolvable Skin Patch Vaccines a Reality?
Overall, dissolvable microneedles patches have many benefits over intramuscular vaccines, yet there are no licensed vaccines using this delivery method in the U.S. Why?
Microneedles are designed to penetrate the epithelial and part of the dermal skin layers. The amount of vaccine a person receives will depend on their skin thickness, amount of moisture in the skin and the size and solubility of the vaccine.
While this variability from human to human is also a challenge faced when administering intramuscular vaccines, it can be overcome by following age and weight recommendations for dosages. These recommendations will be set for each vaccine and its mode of delivery, based on the data accumulated from both the R&D phase and the clinical trail stage.
For dissolvable microneedle delivered vaccines, during the R&D phase, the type of sugar solution (e.g. sucrose or cellulose, etc.) being used and the type of vaccine (mRNA, DNA, or protein subunit, etc.) being delivered will be optimized. During the clinical trail stage, the safety and efficacy in a small group of volunteers will allow for quantifications of human to human variability on the dosage response.
Storage
Because microneedle patches are built to dissolve upon contact with the skin, they must be stored in a dry environment in order to keep them intact prior to administration. In practice, this can be as simple as storing the patches in a desiccant or sealing them until use.
Using a dried sugar and salt solution to carry the vaccine makes most vaccines more stable, but the optimal storage conditions will depend on the type of vaccine (e.g. mRNA, DNA, or protein subunit) being delivered. For example, mRNA vaccines in a microneedle patch may be more stable, but they will still need to be kept frozen, whereas some protein subunit vaccines in microneedles can be kept at room temperature or in a standard fridge.
Sterility
The final challenge to vaccine development is sterility. Sugar is a common fuel source for humans and pathogens alike. Building dissolvable microneedles out of sugar requires the use of sterile techniques and sterile storage to prevent bacterial growth in the vaccine. To overcome this hurdle, standardized laboratory practices and rigorous post-production testing will be needed. This is a challenge for many areas of the food and drug production industry, and many of the techniques can be adapted to produce dissolvable microneedle patches.
Dissolvable microneedle skin patches may face challenges to production, as does any new technology, but the benefits are pushing scientists to develop this new platform for vaccine delivery. There are many vaccines that are currently in clinical trails for delivery through dissolvable microneedle patches, including vaccines against Influenza, MMR and SARS-CoV-2. Keep your eyes open for needle-free vaccines coming soon.
Interested in learning more about vaccine reserach?
Haley Bridgewater, M.S., is a doctoral candidate in the BioMolecular Sciences program at Boise State University working on the development of adjuvanted Staphylococcus skin-delivered vaccines.
