Flu Shots No More?

Flu (Influenza)Flu Shots No More?
NIAID Grantees Use New Skin Patches to Deliver Flu Vaccine in Mice

You’ve probably heard of patches for delivering nicotine-replacement therapy or hormones for birth control. But what about other uses, such as vaccination? For many years, researchers have been working to find a way to deliver flu vaccine – whose components are much larger than those of nicotine and hormones – using a transdermal (across the skin) patch. One method, developed by scientists at the Georgia Institute of Technology and Emory University, uses a new type of patch made of dissolving microneedles, which are tiny, painless needles that allow flu vaccine to pass through the skin.

A new study led by Mark Prausnitz, Ph.D., and Sean Sullivan, Ph.D., of Georgia Tech, and Dimitrios Koutsonanos, Ph.D., Ioanna Skountzou, Ph.D., and Richard Compans, Ph.D., of Emory University, compared microneedle patches to traditional hypodermic needles to vaccinate mice against the flu. The microneedles in this study were made of the polymer polyvinylpyrrolidone, a compound that has been previously tested and found to be nontoxic. The investigators found microneedles to be at least as effective as hypodermic needles, and by some measures, more so. The research was supported by NIAID and the National Institute of Biomedical Imaging and Bioengineering (NIBIB).

Microneedle Patches: A Melding of Engineering and Biology
Dr. Prausnitz’s lab has spent several years studying vaccine delivery. “Our goal is to use engineering technology to solve drug delivery problems,” he explains. “We want to administer vaccines in a way that would be easy for patients.”

The investigators used an innovative method to create the microneedle patches. In a process known as in situ polymerization, they mixed liquid vinylpyrrolidone with the vaccine, poured the mixture into a microneedle mold, and exposed it to ultraviolet light. This induced polymerization, creating much larger molecules.

Once placed on the skin, the microneedles pass through the surface skin layers, moisten, and dissolve, delivering flu vaccine to antigen-presenting cells in the skin. These cells then break down antigens and display them to other immune cells. The body mounts an immune response to those antigens, and is thereby prepared to fight off the virus in the future. When the microneedles fully dissolve – within a few minutes – the patch can be removed and disposed.

Testing Immunity from Microneedle-Delivered Vaccine
After vaccination, the researchers measured flu antibody levels in the blood and found no difference between mice who received the microneedle vaccine and those who received a hypodermic injection. In fact, when vaccinated mice were exposed to flu virus, those that received the microneedle vaccine were significantly better protected than those that received a hypodermic injection. Four days after being exposed, mice in the microneedle group were able to clear the virus out of their lungs 1000 times more efficiently than mice in the hypodermic group.

“Viral load is an important measure because it addresses the source of the problem: virus in the lungs. Microneedle vaccination brought the viral load in the lungs almost to zero,” says Dr. Prausnitz. A reduced viral load may also have implications for the infectivity of flu; if a person expels less virus with a cough or sneeze, transmission may be reduced.

Microneedle patches also have practical advantages over traditional hypodermic injections: they take up less space in clinics, do not require special disposal (as hypodermics do), are inexpensive to make, and may be simple enough for patients to self-administer at home. Because of these advantages, they could have important benefits for public health. If these results can be replicated in humans, not only would people who receive the vaccine be better protected from the flu, but it may be easier for more people to get vaccinated. If more people are vaccinated, fewer people are likely to get sick and be able to pass the virus on to others, lowering everyone’s chances of being exposed.

Looking to the Future
The researchers are currently exploring the reasons why microneedle delivery resulted in reduced viral load in mice. Microneedle skin patches target a different set of immune cells than conventional intramuscular injection, notes Dr. Prausnitz. “I don’t think the improvement in immunogenicity is something unique to microneedles, but rather is unique to delivery through the skin. Microneedles enable that to take place,” he says. In answering this question, they are studying the immunologic pathways triggered by delivery to the skin, and hoping to harness these pathways to improve immunogenicity.

They are also reaching out to experts in other infectious diseases, to test this delivery approach with different vaccines. Dr. Prausnitz cites the growing importance of collaboration in this research. “This study is one of more and more examples where the tools of engineering can be combined with the expertise of bioscientists, to obtain results that would have been hard to get without collaboration.”

Citation:
Sullivan SP, Koutsonanos DG, del Pilar Martin M, Lee J-W, Zarnitsyn V, Murthy N, Compans RW, Skountzou I, Prausnitz MR. (online, 18 July 2010). Dissolving polymer microneedle patches for influenza vaccination. Nature Medicine.
http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.2182.html

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Flu Shots No More?