COVID-19 vaccines might soon be delivered via a microneedle patch if results from an animal model are repeated in humans. A group of scientists has reported the recent breakthrough in the journal ACS Nano.

Both in vitro and in mice, the team reported that a microneedle patch can deliver a COVID-19 DNA vaccine and elicit a strong immune response. The patch can be stored for 30 days at room temperature, making it a lot more versatile in terms of storage than the three vaccines currently authorized in the US, which must be kept refrigerated or frozen.

While this approach still needs testing in humans it would be the first approved COVID-19 DNA vaccine although it wouldn’t be the first one to be needle-free. The other one is ZyCoV-D, an intradermal vaccine applied in three doses via a specific needle-free delivery system, which was approved in India last month.

ZyCoV-D still needs to be refrigerated so the microneedle patch has that specific advantage. This is one of the reasons why this could be a game-changer for immunization, especially in developing countries. Another reason that makes this approach particularly exciting is where it delivers the vaccine.

Conventional vaccines are delivered intramuscularly, but delivery in the skin is believed to lead to better immune responses. Our skin – the human body's largest organ – has an abundance of antigen-presenting cells (APCs), so delivering a vaccine there allows the body to learn about the pathogen in a more effective way. As with the other, intramuscular vaccines, this approach teaches the immune system to recognize the SARS-CoV-2 spike protein – the molecular hook used by the COVID-19 virus to attach itself to the cells before penetrating them. Alternatively, it can also use the virus nucleocapsid protein.

DNA vaccines tend to be more stable and easier to make than RNA ones such as Moderna and Pfizer/BioNTech, but the DNA molecule has more difficulty being taken into the cell nucleus. And that’s why having lots of APCs matters, as it allows a higher chance for the DNA to enter the nucleus of many of these cells.

The microneedle patch is coated with DNA sequences on the surface of non-toxic nanoparticles that help to generate an immune response. The patch is made of 100 biodegradable microneedles, each smaller than one-tenth of a bee-stinger. But unlike a sting, this is completely painless, penetrating the skin's outer layer. In mice, it produced strong antibody and T-cell responses and had no observable side effects.