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 from researchers at Rutgers and the 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 coauthor 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.
However, combining two different adjuvants--aluminum phosphate and short DNA molecules called CpG--boosted both antibody and cellular responses.
The researchers traced part of the benefit to immune signals activated in the skin and nearby lymph nodes. Their findings suggest that selecting the right immune stimulation and delivering mRNA into cells are essential to making this method work.
“One of the most exciting discoveries in developing our carrier-free mRNA vaccines was that a combination of adjuvants could markedly improve vaccine efficacy while maintaining a favorable safety profile in our animal studies,” said senior author Satoshi Uchida of the Institute of Science Tokyo.
After three doses, infectious virus was below detection limits in lung samples from mice given the boosted vaccines and later exposed to SARS-CoV-2 or influenza A. In the COVID-19 experiment, lung viral RNA was about 24 times lower than after vaccination without the adjuvants. Both flu vaccine groups survived, so no additional survival benefit from the boosters was established.
Separate experiments found less local and systemic inflammation than with laboratory lipid-particle formulations of mRNA vaccine.
Despite its success in mice, the new approach still needs testing in larger animals before human trials, including establishing suitable doses.
“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.
Funding for this project was provided by the Japan Agency for Medical Research and Development; the Japan Science and Technology Agency; the Japan Society for the Promotion of Science; the Program for Promotion of Fundamental Studies in COVID-19 of the Tokyo Metropolitan Government; Nanken-Kyoten, Science Tokyo; the Medical Research Center Initiative for High Depth Omics, Science Tokyo; and the Levy-Longenbaugh Donor-Advised Fund.
Disclosure: Satoshi Uchida is a founder and Chief Medical Officer of Crafton Biotechnology Co., Ltd. Renata Pasqualini and Wadih Arap are founders and equity shareholders of PhageNova Bio and of MBrace Therapeutics, and serve as paid consultants. Pasqualini serves as Chief Scientific Officer of PhageNova Bio.
About Rutgers Cancer Institute
As New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, Rutgers Cancer Institute, together with RWJBarnabas Health, provides patients access to the most advanced treatment options, including clinical trials close to home at our facilities throughout the state. Our groundbreaking cancer research is the engine that drives access to the most advanced cancer treatments, where our discoveries become your care. This has been enhanced with the opening of the state’s first and only freestanding cancer hospital, the Jack & Sheryl Morris Cancer Center. Visit: www.cinj.org .
Journal of Clinical Investigation
Experimental study
Animals
Jet-injected combinational adjuvants potentiate naked mRNA vaccines for protection against respiratory viral infections in mice
20-Oct-2026
SU is a founder and Chief Medical Officer in Crafton Biotechnology Co., Ltd. RP and WA are founders and equity shareholders of PhageNova Bio. RP serves as the Chief Scientific Officer and paid consultant of PhageNova Bio. RP and WA are founders and equity shareholders of MBrace Therapeutics and serve as paid consultants. RP and WA have Sponsored Research Agreements (SRAs) with PhageNova Bio and MBrace Therapeutics, which are managed in accordance with the established institutional conflict-of-interest policies of Rutgers, The State University of New Jersey. The work presented in this manuscript falls outside of those SRAs. None of these conflicts affected the experimental design, interpretation, or reporting of the results. Other authors declare that they have no competing interests related to this work.