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. Researchers at Rutgers and Japanese institutions published these findings in The Journal of Clinical Investigation, testing experimental improvements to mRNA vaccine delivery.
High-Pressure Liquid Jet Delivers mRNA Into the Skin
The experimental approach combines a high-pressure liquid jet that delivers mRNA directly into the skin with two substances that strengthen the immune response. Skin is rich in immune cells, making it an attractive target for delivery. Earlier work showed that jet injection could effectively deliver unencapsulated, or "naked," mRNA, but the resulting immune response remained too weak to offer full protection on its own.
Researchers tried to bolster the effect by adding adjuvants, which are substances that enhance conventional vaccines. Unfortunately, these adjuvants offered little benefit when used individually with the mRNA. Some additives actually weakened parts of the immune response instead of helping.
Adjuvant Combination Boosts Antibody and Cellular Responses
To overcome weak single-adjuvant performance, the team combined two different substances: aluminum phosphate and short DNA molecules called CpG. This specific combination successfully boosted both antibody and cellular responses in the treated subjects. The researchers traced part of the benefit to immune signals activated directly in the skin and nearby lymph nodes.
“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 coauthor Renata Pasqualini of Rutgers New Jersey Medical School and Rutgers Cancer Institute.
In the COVID-19 experiment, lung viral RNA was about 24 times lower in boosted mice than after vaccination without the adjuvants. After three doses, infectious virus fell below detection limits in lung samples from mice given the boosted vaccines when they were later exposed to SARS-CoV-2 or influenza A. Both flu vaccine groups survived the challenge, meaning researchers could not establish an additional survival benefit from the boosters for influenza.
Next Steps for Needle-Free Delivery Before Human Trials
Despite success in mice, the new approach still needs testing in larger animals before human trials can begin. Scientists must also establish suitable doses for larger subjects. However, the study authors find encouragement in the specific components used in the experiment.
“What encourages us is that we achieved protective immunity in mice with a delivery device and adjuvant components that have each already been clinically used in human patients,” said coauthor Wadih Arap of Rutgers New Jersey Medical School and Rutgers Cancer Institute.
Questions About Needle-Free mRNA Vaccine Delivery
How does the jet injector deliver the vaccine?
The device uses a high-pressure liquid jet to push unencapsulated mRNA directly into the skin, bypassing the need for a traditional hypodermic needle entirely.
Why were aluminum phosphate and CpG used together?
Individual adjuvants offered little benefit or weakened parts of the immune response when tested alone, but combining aluminum phosphate and short DNA molecules called CpG successfully boosted both antibody and cellular responses.
Are these components already approved for humans?
Yes, coauthor Wadih Arap noted that the delivery device and the adjuvant components have each already been clinically used in human patients, though the combined mRNA delivery method still requires large-animal testing.
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