Monday July 19 2010
The tiny dissolving spikes are only 0.65mm long
“The conventional flu jab could be replaced by a skin patch,” says The Guardian. The patch, which is coated in microscopic dissolving spikes, is designed to deliver the flu vaccine into the skin without a syringe.
The news is based on important research, and the patch’s animal trial has been covered widely. Some papers have focused on the patch as a means of delivering the flu vaccination, while others have concentrated on the potential for the patch to eliminate all injections.
While the technology worked in mice, the immune response and safety issues need to be tested in human trials before this will become an acceptable alternative to intramuscular injections for vaccinating humans. If testing is successful, the patch will be an attractive option because, as many of the newspapers report, it is easier to administer than a normal injection. It might also reduce some of the difficulties associated with traditional mass vaccination campaigns. This is a technology to watch, and more research will undoubtedly follow.
Where did the story come from?
The study was carried out by researchers from Georgia Institute of Technology and the Emory University School of Medicine in Georgia, USA. The research was funded in part by the US National Institutes of Health and was published in the peer-reviewed medical journal Nature Medicine.
The coverage in the papers is optimistic and all herald this as a discovery that could revolutionise the way that vaccines are delivered, so that they can be given without needles and without the need for medical experts. Testing on humans will undoubtedly follow and is the only way to assess the full potential of this new technology.
What kind of research was this?
This was a laboratory study in mice, that assessed the efficiency of delivering a flu vaccine intradermally (into the skin) using patches coated in dissolvable microneedles. Some studies have shown that intradermal vaccination is better than intramuscular injections, although this finding has not been consistent across research.
The tiny spikes soon disolve into the skin (magnified)
The researchers say that the effectiveness of a flu vaccination is limited by the quality of the immune response and by how long it takes to deliver the vaccine. The study was motivated by the consideration that vaccination against influenza would benefit from a method that simplified the distribution and administration of the vaccine, in particular one that avoided the dangers posed by hypodermic needles.
The problems inherent in using hypodermic syringes include the relatively common phobia of needles, which can make even a vaccination a traumatic event for some, as well as the biohazardous waste produced, which needs to be disposed of carefully. Finding a solution to these issues could enhance the success of vaccination programmes.
What did the research involve?
In this study researchers compared standard intramuscular approaches to vaccination with the use of a dissolvable microneedle patch as a means of delivering inactivated influenza vaccine to mice. The patch was coated with about 100 ultrafine microneedles, measuring 0.65mm in length, that collectively delivered 3µg of inactivated influenza virus.
The microneedles were moulded at room temperature out of a highly water-soluble substance called polyvinyl pyrrolidone and the freeze-dried vaccine. This means that the patches can be transported cheaply and easily as they do not need to be kept in a fridge after manufacture, another problem with injectable liquid vaccines.
The researchers tested the application of the patch on pig skin to see how much force was needed to pierce the skin and to what depth the needles penetrated. They were also interested in where the needles deposited the vaccine, in order to confirm that this was largely within the skin layer as intended. They also determined how long the needles took to dissolve.
They then went on to test the patch in living animals (mice), testing the penetration and how long the needles took to dissolve. They were particularly interested in testing the effects of freeze-drying the flu virus and its addition to the microneedle polymer. To determine whether the process had damaged the virus, they compared the immune responses of live mice given one of four different administrations: normal intramuscular vaccination, a freeze-dried vaccine (the first step in preparing it for formation into the microneedles), a freeze-dried vaccine mixed with the polymer solution or a virus moulded into polymer needles.
In a further set of experiments they tested whether the vaccine worked to prevent influenza when delivered via the microneedle patch. Mice received a single dose of vaccine via the patch, which was placed on the skin for 15 minutes. They compared the full immune response (that is, presence of influenza-specific antibodies 14 and 28 days after vaccination) and whether the vaccination protected the mice from flu when they were exposed to very high levels of flu virus 30 days after vaccination.
Finally, the researchers compared delivery using their dissolving microneedles with delivery by metal microneedles coated with the vaccine.
What were the basic results?
The researchers note that the patch is likely to penetrate human skin to the same degree as it did pig skin (which is of similar thickness). About 89% of the needle mass had disappeared after five minutes. When inserted into living mice, the needles dissolved more slowly but had nearly disappeared by about 15 minutes.
The vaccine preparation process did not alter the effectiveness of the vaccination, which was gauged using the strength of immune response that it produced in mice. The vaccine patch compared well with traditional intramuscular delivery, and levels of antibodies 28 days after the vaccination were similar to those seen in mice vaccinated intramuscularly.
When the mice were exposed to the flu virus, mice who received vaccination using the patch had a better cellular response than other mice and were able to clear an infection from the lung more efficiently. Overall, the dissolving microneedles were better than traditional intramuscular injection and offer advantages over coated metal microneedles.
How did the researchers interpret the results?
The researchers say that, overall, their results show that dissolving microneedle patches offer an attractive approach to administering influenza vaccine. They note that the technology offers “improved safety, immunogenicity [immune response] and logistical operations” that they say may enable increased population coverage for influenza vaccination.
This well-conducted and well-reported laboratory and animal study describes the early investigations into a new technology to deliver the influenza vaccine. Research in mice has produced good results, and the technique compares well with the traditional intramuscular approach to vaccination. The patch is also seen to penetrate pig skin (which researchers note is of similar thickness to human skin) to the required degree and to dissolve well.
The technology may allow the simple administration of other vaccines and medicines to the skin without the need for hypodermic needles, although human studies will demonstrate its real value. Studies in humans look likely given the importance of this laboratory research and the potential this technology may hold.
There are a few other points to note:
- This research only looked at vaccines against the influenza virus, which use deactivated or ‘dead’ viral particles to induce an immune response. Other types of vaccine, particularly ‘live vaccines’ that feature weakened versions of viruses may not be effective when delivered using this method. This question will also need to be addressed through further research.
- Newspaper reports suggest that future vaccinations using this method might not need medical supervision but, again, this will need testing if human trials eventually confirm that patches are effective.
- The costs involved in this method are unclear, and it may prove less cost-effective than intramuscular vaccination. However, it does appear to avoid some of the expensive practicalities that come with traditional vaccines, such as the need for constant refrigeration.