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A needle-free vaccination method protected mice against the viruses that cause COVID-19 and flu, offering a possible new way to deliver mRNA vaccines while limiting unwanted inflammation.

The Journal of Clinical Investigation study by researchers at Rutgers and Japanese institutions tests experimental improvements to mRNA vaccine delivery. The approach combines a high-pressure liquid jet that delivers mRNA into the skin with two substances that strengthen the immune response.

"Showing that a carrier-free, needle-free vaccine can be made protective opens a different design space than the one the field has been working in," said co-author Renata Pasqualini of Rutgers New Jersey Medical School and Rutgers Cancer Institute, New Jersey's only National Cancer Institute-designated comprehensive cancer center, together with RWJBarnabas Health.

mRNA vaccines give cells temporary instructions to make a protein that trains the immune system to recognize a threat. In existing vaccines, tiny fat-based particles form capsules around the fragile mRNA, helping it enter cells and stimulate immunity.

The researchers explored another approach: delivering unencapsulated, or "naked," mRNA into the skin, which is rich in immune cells. Earlier work showed that jet injection could effectively deliver mRNA, but the resulting immune response was weak.

Researchers tried to bolster the effect by adding adjuvants, substances that enhance conventional vaccines. Unfortunately, these adjuvants offered little benefit when used individually with the mRNA. Some actually weakened parts of the response.

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