3D-Printed Vaccine Patch Offers Enhanced Immune Response, Comfort Level

3D Patch/courtesy UNC

3D Vaccine Patch/Courtesy of University of North Carolina School of Medicine.

A vaccine patch that generates an immune response ten times greater than that of a traditional intramuscular injection has been developed by researchers at the University of North Carolina at Chapel Hill and Stanford University. Its T-cell and antigen-specific antibody response is even greater. That’s 50-fold higher than with subcutaneous injections. Consequently, the patch is not only painless, it requires less vaccine to generate the same or greater effects.

This 3D-printed patch enhanced vaccine retention in the skin and increased immune cell activation in the lymph nodes. That was evidenced by higher total levels of immunoglobulin G (IgG), more balanced IgG1/IgG2a and more functional cytotoxic CD8+ T cells and CD4+T cells secreting T helper type 1 (TH1) cytokines.

The patch consists of 700 µm PEG microneedles 3D-printed on a 10x10mm polymer patch. The needles were coated with vaccine and then the patch was placed on the skin. The result is a painless, less invasive vaccine delivery method that can be administered by patients themselves without the need for medical personnel. Details appeared recently in Proceedings of the National Academy of Scientists.

As lead author Shaomin Tian, a researcher in the department of microbiology and immunology in the UNC School of Medicine, told BioSpace, there are two key mechanisms that make the vaccine patch more effective than standard intramuscular injections.

First, she said, “skin is the first line of bodily protection. The density of cells that sample invading pathogens is 1,000 times higher (in skin) than those found in the muscles. Therefore, intradermal vaccination via microneedles inherently targets the vaccines to the rich immune cell populations in the skin and (thus) helps mount faster and stronger immunity.”  

Furthermore, Tian continued, “the dry solid film microneedle vaccines are specially formulated with highly viscous components. Upon vaccine administration, an antigen depot can be formed that supports sustained antigen exposure to immune cells, and therefore, helps induce stronger immune responses.”

This delivery method can be adjusted to deliver many different vaccines or biologics (including mRNA vaccines) for COVID-19, seasonal influenza, measles, hepatitis and other conditions. Importantly for global distribution, microneedle formulations are stored in a dried form, so there is no need for vaccine reconstitution, or possibly, for cooling during shipping and storage. The researchers are collaborating with VLP Therapeutics to formulate RNA-based microneedle patch vaccines.       

“Custom formulation of various types of vaccines – including mRNA – on microneedle patches requires upfront investigation time,” Tian pointed out. “We anticipate that once standardized formulations are established for each class of vaccines (which we are now working on), this will be a quick process, especially for already approved vaccines.”

The next step will be to test those microneedle formulations and the patch in non-human primates. Ultimately, Tian said, “I envision a normal regulatory review process, including evaluation of the vaccine safety and efficacy/protection, will still be required for microneedle patch-based mRNA vaccine formulations.”

The other key challenge to commercialization is manufacturing the patches in massive quantities under GMP conditions. “This could be addressed relatively easily by establishing clean manufacturing facilities that house large numbers of 3D printers for mass fabrication,” she suggested.

The anticipated benefits are likely to outweigh any challenges, though. Design flexibility is one of the key benefits of 3D printing vaccine patches. The 3D printing process enables the microneedles to be sharper – and thus yield more reproducible results – than is possible when using the traditional master templates and molds used to make microneedles commercially today. This new method also enables needles with different shapes to be included on the same patch to avoid what the authors called a “bed of nails effect.”

This novel 3D printing process uses continuous liquid interface production (CLIP) technology developed by study author Joseph M. DeSimone, professor of translational medicine and chemical engineering at Stanford University and professor emeritus at UNC-Chapel Hill. CLIP technology created faceted microneedles with greater surface area than the smooth square pyramidal design. This difference allowed the needles to carry more vaccine than traditional microneedles – 27.6 μg vs 20.3 μg ovalbumin, for 36% higher loading.

Additionally, CLIP “allows the direct fabrication and rapid screening of a multitude of microneedle properties (such as geometry, composition and density) in an iterative design process, with the need to consider the parameters associated with mold filling or the limitations of needle geometries that cannot be molded,” the authors wrote.

Because microneedle patch vaccinations are painless when compared to traditional hypodermic needle injections, “this would be an ideal vaccination approach for children, the elderly and those who may have needle phobia. It thus could help enhance the vaccination rate,” Tian speculated.

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