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Microbial Superglue May Lead To Faster, Safer Vaccines

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VACCINE
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The development of a vaccine is a rather long and complicated process. Also, it isn't always successful. While we may hear of great advancements in the media, such as last year's successful trial of the Ebola vaccine, usually the news comes after decades of work in the laboratory examining potential candidates. Taking the Ebola vaccine as an example, the first attempts occurred nearly two decades ago.

The trouble with vaccine development is not a result of scientific error but rather due to the complex nature of the immune system and its ability to respond to a threat. Three specific criteria need to be met in order to attain a proper vaccine candidate. If any one of these proves to be too great, the entire process may be stopped.

The first hurdle is rather simple in nature: the candidate has to efficiently stimulate the immune system. This trait is known as immunogenicity and is the hallmark of any vaccine. Unfortunately, finding a proper type or strain may be difficult at best and in some cases, such as the common cold-causing rhinoviruses, may be almost impossible.

The second obstacle involves another branch of the immune system, memory. A candidate must have the ability to provoke the immune system such that it wants to remember the pathogen should it ever come again. Usually, one shot can achieve this memory, but in some cases, such as hepatitis B virus, memory can be lost over time. This hurdle can be managed with multiple vaccinations over time, also known as boosters.

The final step in vaccine success happens to also be the first in terms of clinical testing. The vaccine needs to be safe. This is perhaps the greatest hurdle as the results will determine whether the public will raise shirt sleeves instead of doubts. Indeed, in today's overly concerned society safety is perhaps the greatest threshold in terms of acceptance.

Finding the right vaccine candidate to achieve all three steps is obviously difficult, and many options have been identified to ensure success. Many vaccines are based on the whole organism, but some rely solely on pieces of the pathogen, such as a protein. This route focuses not on the whole, but on the sum of one or more parts. It's also the most effective in terms of safety as the risk for side effects declines significantly.

Last week, an international team of researchers unveiled new means to make vaccine candidates from proteins.

But this path is difficult as significant work in the lab is needed to put the protein into a safe and effective vehicle for injection. This could mean adding a modified version of the protein directly into the body, such as tetanus toxin, or cloning the protein into a harmless virus as seen in the most recent Ebola vaccine candidate. Both routes are difficult to accomplish and take significant time to develop.

But there may be a new way to develop these vaccines safely. Last week, an international team of researchers unveiled new means to make vaccine candidates from proteins. Instead of trying to modify or clone the proteins, these researchers have come up with an entirely new concept: they use bacterial superglue.

The glue in this case isn't the same as the white stuff you find in kindergarten classrooms. It's made up of amino acids, the building blocks of proteins. When the right combination of these molecules is put together, it attaches so tightly that it's almost impossible to break. For the researchers, this seemed to be an excellent route towards vaccine development.

The process was rather straightforward. The team first inserted some of the glue-like amino acids into the vehicle of choice, a harmless virus of bacteria (bacteriophage) known as AP205. The other sticky amino acids were added to the vaccine candidates, in this case, proteins from a rather nasty infection, malaria. Once this was accomplished, the phage and the malarial protein were put together overnight and allowed to stick together.

The next and most important step was to determine if the new vaccine concept actually worked. The team injected the sticky mix into mice and then followed the animals' immune responses. Sure enough, the mice developed both an immune response and memory, meeting the first two criteria. Best of all, there were no side effects, suggesting the process was safe.

The authors suggested this new method for vaccine development may be useful in two ways. First, it provides an easy and quick route to screen vaccines to reduce the time needed to get to animal and clinical trials. But more importantly, the superglue method may offer a way to vaccinate individuals in a completely safe manner such that the risk for side effects -- and doubt -- is even further minimized. In light of the current need for rapid vaccine development, the superglue may be the answer we need.

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