Research Finds Needleless Flu Vaccine Patch to be Effective

Researchers from the University of Rochester Medical Center have recently created a needleless patch that effectively vaccinated mice for the flu in a preclinical study. This work, published in the Journal of Investigative Dermatology,  found that this innovative patch triggered an immune response that closely resembled that of a traditional flu shot with no side effects. The patch’s success in this animal study is an important step in the development of an alternative to needle-based vaccines.

“Scientists have been studying needle-free vaccine approaches for nearly two decades, but none of the technologies have lived up to the hype,” said Benjamin L. Miller, PhD, corresponding author and Dean’s Professor of Dermatology at the University of Rochester Medical Center. “Our patch overcomes a lot of the challenges faced by microneedle patches for vaccine delivery, the main method that’s been tested over the years, and our efficacy and lack of toxicity make me excited about the prospect of a product that could have huge implications for global health.”

Challenges in Crossing the Skin Barrier

Being that the protein molecules in the flu vaccine are particularly large, they are unable to naturally diffuse through the skin. To address this issue, Miller and colleagues looked to an existing skin disease that causes patients to have excessively permeable skin. Atopic dermatitis, also known as eczema, is a condition characterized by a leaky skin barrier that allows mold, pollen, and other allergens to pass through the skin and trigger the immune system.

Corresponding author Lisa Beck, MD, found that the expression of the claudin-1 protein contributes to the normal barrier strength of the skin. This protein is expressed much less in patients with eczema, leading to the skin permeability seen with this disease, and Beck has noted through previous research that decreasing claudin-1 expression in healthy skin cells makes the skin more permeable.

Alongside Miller and first author Matthew Brewer, PhD, Beck aimed to modify this claudin-1 expression to possible allow the flu vaccine to permeate the skin. The skin’s permeability must be increased for just long enough for the vaccine to enter, but not so long that unwanted allergens can cross the skin barrier.

Creating the Needleless Flu Vaccine Patch

Miller and Brewer collaborated to create synthetic peptides that bind and inhibit claudin-1. They tested this compound in human skin cells to ensure that it could increase permeability without inducing any toxicity as well. After doing so, they created a patch that contains this synthetic peptide and a flu vaccine and tested it in two different scenarios.

The first of which involved the use of the patch in mice to prime their immune system, followed by an administration of a flu shot to boost their immunity. The second case involved these same procedures in reverse order. The flu patch was placed on the backs of the mice for 18-36 hours in this study and was found to effectively increase the skin’s permeability as measured by water loss.

patchThere was no significant immune response when the patch was administered before the injection, indicating that it may not be successful as one’s first vaccination for the virus. In the patients who received the injection first and the patch second, however, there was a profound immune response to the patch. This indicates that the patch could enhance preexisting immunity in a manner that mimics the seasonal flu shots we get every year. There were no adverse effects seen in the skin during the three months of observation as well, indicating that the permeability did not linger and produce unwanted side effects.

“When we applied the patch with the peptide the mouse skin became permeable for a short time,” said Brewer, a postdoctoral fellow in both the Beck and Miller labs. “But as soon as the patch was removed the skin barrier started to close. We saw significant differences as early as one hour after removal, and by 24 hours the skin was back to normal, which is great news from a safety standpoint.”

Going Forward

The team notes that further preclinical research is needed before the patch can be administered to humans, particularly to optimize the amount of time the patch must remain on the skin. They hope to advance into clinical trials soon and are confident that the patch could be used to replace various injected vaccines if found to be effective.

This patch has the potential to greatly enhance vaccination efforts in developing countries as well, being that they do not require a trained professional to be administered. Being that the patch doesn’t have to be refrigerated or prepared in solution using equipment, it can be administered by anyone.

“These countries don’t have the manpower to vaccinate entire populations,” said Beck, who is also the Dean’s Professor of Dermatology at the University of Rochester Medical Center. “On top of that, there’s an aversion to health care in many of these communities. A needle is painful, it’s invasive, and that makes things more difficult when you are dealing with a cultural bias against preventative medicine.”

“If you want to vaccinate a village in Africa you don’t want to do it with needles,” added Miller. “A patch doesn’t have to be refrigerated, it can be applied by anyone, and there are no concerns about disposal or needles getting reused.”