Skin stretching enables needle-free vaccine delivery in mice

Researchers show that stretching the skin stimulates immune cells and increases the skin’s ability to absorb large molecules, including those present in vaccines. Publishing September 17 in the Cell Press journal Cell Reports, they report that applying vaccines topically while stretching the skin resulted in more effective immunization than subcutaneously injecting the vaccine in mice. 

“You should be really careful about what you apply on your skin,” says senior author and immunologist Elodie Segura of INSERM, France. “We showed that we can use this pathway into the skin for vaccine delivery, but it could also allow the penetration of toxic compounds or stimulate inflammation or allergy.” 

When receptors within the skin detect injuries, they stimulate an immune response. Other skin receptors detect stretching—which occurs during massage or when skin care products are rubbed in, but it was unclear whether skin stretching without damage could also activate the skin’s immune system. 

To examine the impacts of skin stretching on skin permeability and the immune system, the researchers used a device that stretches the skin by applying suction pressure. When applied for 20 minutes, the device temporarily increased the permeability of both mouse and human skin to fluorescently labelled large molecules by rearranging the skin’s collagen fibers in a way that caused the hair follicles to open. The skin retained its usual impermeable nature after around 15 minutes.  

The team also showed that skin stretching activates a local immune response. In mice, the device resulted in an increased number of immune cells within the skin 24 hours later, suggesting that immune cells were migrating to the skin in response to stretching. Stretching also triggered changes in gene expression for more than 1,000 genes, including several genes that encode immune signaling molecules (cytokines). 

“It was quite surprising—I would not have expected so much production of inflammatory molecules just from stretching the skin,” says Segura. 

To test whether these changes in immune surveillance and skin permeability could enable needle-free vaccine delivery in mice, the researchers applied a topical lotion containing a fluorescently labeled flu vaccine in conjunction with the skin-stretching device.  

The vaccine’s fluorescent marker revealed a slow, controlled uptake of the vaccine into the mice’s bloodstreams and an accumulation of vaccine antigen in nearby lymph nodes, which is where immune responses are coordinated. 

Compared to intramuscular vaccine delivery, the needle-free method resulted in higher antibody levels against the H1N1 flu antigen. Including an adjuvant in the vaccine formulation (a chemical that enhances immune response to vaccination) did not improve the immune response when the vaccine was delivered via the skin, suggesting that skin-stretching alone was sufficient to boost immunization. 

“Just stretching the skin was more effective than delivering the same vaccine with a needle, which shows the practical relevance of this immune activation,” says senior author Stuart Jones of King’s College London. “This new pathway into the skin could be used in lots of different ways—we showed its potential for vaccine delivery, but we're also starting to think about delivering cell therapies and whether it could be used for diagnostics.” 

Because most of these tests were conducted in mice, more work is needed to examine whether skin stretching results in similar immune activation in humans and whether it could facilitate vaccine delivery. The team also plans to investigate whether this skin-opening pathway could stimulate unwanted immune responses or allergies. 

“Human skin is usually much less permeable than mouse skin because it has a thicker outer layer, but in this case, it responded in the same way because the molecules are moving through the hair follicles, not through the outer skin layer,” says Jones. “We believe this gives a really solid foundation for our results to be translated into humans.” 

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This research was supported by funding from INSERM, the Agence Nationale de la Recherche, the European Joint Programming Initiative, the European Research Area Networks (ERA-NET) Cofund, and the Engineering and Physical Sciences Research Council (EPSRC). 

Cell Reports, Benaouda et al., “Transient skin stretching stimulates immune surveillance and promotes vaccine delivery via hair follicles” https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00995-7

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