Research Profile - Getting under the skin

Vaccines do enormous good, protecting broad swathes of the population from infectious diseases. But there's always room for improvement.

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When Edward Jenner first induced immunity to smallpox, back in 1796, he did it by scratching the skin to allow small amounts of the cowpox virus to enter the body. (Cowpox, which isn't fatal to humans, is closely related to smallpox). Today, most vaccines are administered by injecting them into a muscle.

This method of vaccination has worked for many years, but it's not problem-free. Often, multiple shots are needed to provide protection. This situation is far from ideal with hard-to-reach populations, for whom giving one shot is enough of a challenge, much less two or three shots. And, vaccines simply don't work for everyone. For instance, 10% of people who are immunized for hepatitis B never become immune, no matter how many shots they have.

Jan Dutz wants to change the way we deliver vaccines, to help overcome these problems. The University of British Columbia researcher is examining whether it could be more effective to deliver vaccines through the skin and whether making changes to the skin could make vaccines more effective.

First, he says, you need to understand how vaccines work. When your body senses inflammation, it suspects infection and sends out an immune response. So when a vaccine is administered, the resulting inflammation is a good thing. It tells the immune system to start responding. The immune system forms antibodies to the infectious agent that's been introduced by the vaccine. Those antibodies are what provide people with immunity against that specific infectious disease, whether it's chicken pox, measles or influenza.

But too much inflammation, though, isn't quite so good. Dr. Dutz's lab is trying to improve vaccine design to elicit a stronger immune response with less inflammation, by gaining a better understanding of the skin's immune system.

"People moved away from the skin [in vaccine delivery] because of inflammation," says Dr. Dutz. "But people who don't respond to the hepatitis B vaccine delivered by needle respond when it's delivered under the skin. And you can use much less vaccine – about 80% less in the case of the influenza vaccine."

Dr. Dutz isn't looking at vaccines directly. Rather, he's looking at how vaccines can be improved by other means. Some vaccines use adjuvants, such as alum, to make them more effective. But Dr. Dutz has a different strategy, using creams that, when applied to the skin, make it more responsive to vaccines.

"They fool the immune system into thinking there's a viral infection going on at the time of injection," he says. "And they don't cause as much inflammation as adjuvants."

The creams also offer more flexibility. For example, using the cream three times a day after injection improves the immune response. But if someone finds the cream irritating or that it causes too much inflammation at the site of the injection, they can simply use it once a day.

So far, Dr. Dutz has conducted preliminary trials of creams that will make vaccines more effective. He wants to continue with further trials.

The Study

Dendritic cells are specialized cells found in the skin whose job is to activate the immune system. Other skin cells can also produce inflammatory cells called cytokines that interact with the dendritic cells. When they encounter a vaccine, these cells regulate the production of T-cells, the cells that create antibodies in response to the vaccine. Dr. Dutz is using mice to learn more about this response and about how topical creams can increase the response. His work will help in optimizing strategies to make vaccines and the vaccination process more effective.

"It's such an accessible area and there are so many immune responsive cells in the skin – it's very exciting."