Defending against other pathogens
It's not only viruses that have developed ways to evade the immune system. Other pathogens can be just as tricky, says Dr. Tony Schryvers, who for the past 18 years has been studying bacterial infections and developing vaccines to prevent them.
"Our current focus is trying to overcome the bacteria's strategy of evading the host's immune response. Bacteria have decoy antigens that draw the immune response away from the preferred antigens. Even individual protein antigens have decoy regions to fool the immune system. We've developed an innovative strategy to get around this trickery."
The first step in getting through the fog is to identify the important regions of the protein antigen-the ones that must interact with host proteins in order for the bacteria to survive. "In many cases, researchers didn't know precisely what the antigens used in vaccine development did," explains Dr. Schryvers. "In our situation, we know exactly what the antigen does, and why it's so critical for survival of the bacteria."
The bacteria that Dr. Schryvers studies have developed a mechanism for obtaining iron from the host they have infected. They require iron to live, and they get it from two proteins, transferrin and lactoferrin. The specialized bacteria are responsible for a number of important diseases, including gonorrhoea and meningitis, as well as ear and lung infections.
Dr. Schryvers and his team have identified and described the pathway that transfers iron into the bacterial cell. The first step requires receptors on the surface of the bacterial cells to bind with transferrin or lactoferrin. "This gives us a clear target for a vaccine. It's the Achilles heel of these types of bacteria, and we're exploiting it. The beauty of this vaccine is that it should work for all the diseases caused by this type of bacteria."
Of course, there's still a lot of work to be done. Team members are studying the interaction between the receptors on the bacteria and the host's iron-binding proteins. The detailed structural and functional information from this work will allow them to distinguish decoy regions from regions that are required for function. The team then will use protein engineering to design an antigen that lacks the decoy regions. It should be able to stimulate the appropriate immune response.
"We've done preliminary experiments to show that the regions we want to target can produce an immune response that protects against very different strains of bacteria," says Dr. Schryvers. "I've assembled a team of experts in various fields, including protein crystallography, nuclear magnetic resonance , protein engineering, and immunology. We're coming at this from different angles, but our goal is the same: to develop an effective, broad-spectrum, long-lasting vaccine."