Future flu vaccine: skin patch with tiny, soluble needles?

Jul 19, 2010 (CIDRAP News) – A study published yesterday raises the possibility of a new influenza vaccine platform that replaces the traditional hypodermic needle with a small skin patch studded with dozens of tiny needles that poke painlessly into the skin and dissolve, delivering the vaccine to the skin's specialized immune cells.

Researchers from the Georgia Institute of Technology and Emory University say the new "microneedle" patch could end the need for trained personnel to administer vaccines, eliminate sharps disposal issues, and, on the basis of testing in mice, perhaps provide better immunogenicity.

The technology and the mouse testing are described in an ahead-of-print report published by Nature Biotechnology. The senior author, Mark R. Prausnitz, is a professor at both schools and also a consultant and inventor working with companies that are developing microneedle-based products.

"Overall, these results show that dissolving microneedle patches offer an attractive approach to administer influenza vaccine with improved safety, immunogenicity and logistical operations that may enable an increased population coverage for influenza vaccination," the researchers write. They add that the microneedle patch also could be used to deliver other vaccines and medicines.

Intradermal flu vaccination—injecting flu vaccine into the dermal layer of the skin instead of all the way into muscle—has been considered and tested for years, but no intradermal vaccine has been approved in the United States. Last year, however, the European Union approved an intradermal flu vaccine made by Sanofi Pasteur, which uses a shielded needle that penetrates only 1.5 millimeters.

The new report says patches with nondissolving microneedles made of metal and silicon have been tested in animals, and soluble microneedles for administering drugs have been tested. But vaccination using this approach has not been studied before, the authors say.

If the experimental platform eventually reaches the market, it would join FluMist, the intranasal vaccine, to become the second flu vaccine formulation not requiring a conventional hypodermic needle.

To make the vaccine patch, the researchers mixed freeze-dried flu vaccine with a polymer material called polyvinyl pyrrolidone, which has been shown to be safe in the body, according to a Georgia Tech press release. It says the patches could be mass-produced at about the same cost as conventional needle-and-syringe formulations.

The patch used in the study was an array of 100 needles 650 microns in length, according to the release. When the patch is pressed into the skin, it dissolves quickly, leaving the water-soluble backing, which can be discarded.

In the study, the researchers treated one group of mice with the vaccine patch, another group with a conventional needle vaccine, and a control group with a microneedle patch containing no vaccine. All the mice were infected with flu 30 days later, after which the two vaccinated groups remained healthy, while the control mice died.

In a further test, groups of mice were vaccinated with the microneedles or conventional needles and were exposed to flu 3 months later. Mice in the microneedle group cleared the virus from their lungs more efficiently than the other group, indicating better immunologic recall, according to the report.

The investigators also assessed the mice's humoral (antibody) and cellular immune responses to the microneedle and conventional immunizations. They concluded that the two groups had similar responses by some measures but that the responses in the microneedle group were stronger by other measures.

"Overall, microneedle immunization yielded enhanced recall cellular immune responses, increased numbers of antibody-secreting cells and, notably, more efficient viral clearance," the report states.

Gregory Poland, MD, a flu vaccine expert at the Mayo Clinic in Rochester, Minn., who was not involved in the study, hailed the new vaccine platform as an exciting development.

"I think this is very exciting, for a couple of reasons," he said. "The skin is populated with large numbers of Langerhans dendritic cells—primary antigen-presenting cells—and taking advantage of those is a good thing to do."

In addition, he said, it appears that the microneedle patch "will be relatively inexpensive to develop, manufacture, and distribute."

Also, the patch promises to be very easy to use. "Literally you're putting a patch on that's less than the size of a penny," he said. "That really would not require a sophisticated healthcare setting or trained healthcare workers. And that's always been a limitation of the trivalent inactivated [conventional] vaccine. You have to have a reasonably highly trained healthcare worker to deliver it one at a time."

Poland added that the patch also seems to be an antigen-sparing approach. Doses of 3 to 6 micrograms were used in the study, as compared with 15 mcg for each viral strain in a conventional vaccine, he said.

But he also noted several caveats.

"This is a small mouse study, and whether the findings would translate into humans is always unclear until the research is done," he said, adding that, as with any new vaccine, clinical studies will be necessary to demonstrate the vaccine's safety, immunogenicity, and efficacy.

Also, Poland said, "One would need to know that repeated application of a technology like this wouldn't induce increased local side effects. One could imagine revving up dendritic cells on your arm, and then repeating that another season at the same site, causing an increase in local side effects."

Other questions include how well the approach would work in elderly people, who have fewer dendritic cells and less elasticity in their skin than younger people, and in those who are immunocompromised, he said.

Poland said a number of studies have looked at intradermal delivery of flu and hepatitis B vaccines, with varying results. "Many think the technique involved in taking a syringe and injecting it intradermally is somewhat sophisticated and very hard to do," he said. "This patch idea gets around that problem because it wouldn't require any training to use."

Sullivan SP, Koutsonanos DG, del Pilar Martin M, et al. Dissolving polymer microneedle patches for influenza vaccination. Nature Med 2010 (early online publication Jul 18) [Abstract]

See also:

Jul 19 Georgia Tech press release
http://gtresearchnews.gatech.edu/dissolving-microneedles-patch/

Feb 26, 2009, CIDRAP News story "Europe approves Sanofi's intradermal flu vaccine"

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