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A “Killer” Discovery to Change the Future of Vaccinations

Imagine hiking through the woods and stumbling upon a brand-new car—a car that’s just idling, waiting for someone to grip the wheel and tear out of the forest. Chemistry professor Dr. Paul Savage likens this example of a fortuitous find to the discovery of a game-changing cell he and his colleagues began studying in the human body fifteen years ago.

The ‘car’ they found is the natural killer T cell (NKT cell).  NKT cells are a type of white blood cell naturally found in the body. When NKT cells encounter a specific type of molecule, usually a ‘tag’ (also known as an antigen) on the surface of a virus or a bacterium, they kick-start the immune system so that other white blood cells are alerted to look for foreign antigens and destroy them.

The immune response when an NKT cell is triggered is extremely potent, and it makes sense that researchers would want to take advantage of its powerful abilities to help the immune system to search out and destroy disease-causing organisms.

However, initially the role of NKT cells was unclear. “It hasn’t been understood what the NKT cells respond to or what exactly they do,” Savage said. “Our research is figuring out what gas you put into the car. And when you start it, what does it do?”

Savage—along with other scientists from Georgia Tech, Scripps, and the University of Chicago—have discovered a revolutionary way to trigger NKT cells and dramatically increase the efficacy of vaccines.

First, it’s important to understand how vaccines work: a vaccine contains a weakened version of a disease-causing antigen that that the body will attack, even though the antigen poses no real threat. By attacking the antigen, the body teaches itself how to fight off future organisms with the same antigen, before the real versions of those antigens actually get you sick!

Unfortunately, tricking the immune system into responding to bacterial antigens—like tuberculosis or pneumonia—is complicated. The body tends to ignore bacterial antigens or only generate weak responses.

“Bacteria figure out ways to live with us, infect us, and sometimes kill us without allowing the immune system to generate a good response,” Savage said. “If you get a viral disease and survive it, you won’t get that viral infection again because the immune system [responds well to viruses]. It’s very difficult to get that same response to bacteria.”

Bacteria can evade the immune system’s detection because they surround themselves with repeating chains of sugars, and the immune system generally does not generate strong responses to sugar chains.

To get the immune system to recognize pneumonia bacteria, Savage and his team made a bacterial vaccine that looks like a virus. They covered this fake virus with a one-repeat version of the sugar that normally would have been in a repeated chain on a pneumonia bacterium. They also added a particular antigen for NKT cells, which kick-starts the immune response. Because the vaccine looks like a virus and has only one repeat, the immune system responds to it and learns to recognize that same sugar when it’s found on bacteria.

“[The vaccine] is extremely potent” Savage said. “The results have been spectacular. Our approach is much better [than currently used vaccines]. It’s almost non-comparable. We speculate that we can do this for almost any type of bacteria.”  So far, their tactic has been successful in animal testing.

Savage hopes that these vaccines using NKT cells can eventually be put on the market. In the meantime, he’s enjoying the process of research and discovery.

“It’s really beautiful chemistry,” he said.

—Lia Ludlam and James Collard, College of Physical and Mathematical Sciences

By James Collard and Lia Ludlam Posted on