Understanding the immune system
One of the reasons for the great strides in vaccination is our increased understanding of the human immune system. "Without detailed knowledge of the immune system, it's impossible to develop a vaccine in a rational way," says Heritage Senior Scholar Dr. Babita Agrawal, a researcher at the University of Alberta. "That's why when you read papers by vaccine researchers like me, you're likely to read more about the immune system than about a vaccine. Although the amount of information about the immune system has exploded in the last 20 years, the system is very complicated, and there's a lot we still don't understand."
The immune system offers two types of immunity. Innate immunity is the first line of defence against infectious agents. Some immune cells respond to pathogens in a generic way-they don't recognize specific invaders. This type of response does not result in long-lasting immunity. Adaptive immunity is different-it remembers particular infectious agents and so can prevent reinfections. Vaccination works with this type of immunity.
Adaptive immunity relies on the ability of immune cells such as T cells and B cells to distinguish between the body's own cells and unwanted invaders. They do this by recognizing specific antigens on the surface of bacteria, virally infected host cells, or tumour cells. Specialized immune cells, called dendritic cells, process antigen material and present it to T cells. Once activated, the T cells then search out and destroy any cells that have the type of antigen that was presented to them.
One of Dr. Agrawal's main research interests is the hepatitis C virus. Approximately 3% of the world's population has been infected with hepatitis C. Most infections become chronic and can lead to cirrhosis, liver cancer, other liver diseases, and death. Sustained antiviral therapy can help, but it does not cure the disease.
"There's a desperate need for two kinds of hepatitis C vaccine: a prophylactic vaccine, one that prevents the immunized person from getting the disease, and a therapeutic vaccine, one that is given to already infected people, so they can fight off the infection," says Dr. Agrawal. "I'm working on both types of vaccine in my lab. We are looking at basic immune-system mechanisms, as well as how hepatitis C evades the immune system."
Hepatitis C is somehow able to get past the body's defences initially and establish itself in the body. As the infection moves into the chronic stage, the immune response weakens and becomes less effective. Dr. Agrawal believes the key to understanding how this happens will come from figuring out what might be wrong with the dendritic cells and the T cells. "Are the dendritic cells dysfunctional? Are the T cells not stimulated? Are the T cells stimulated but not functioning? What kind of immune response is required to get rid of the infection from the body? It will take a series of baby steps to answer these questions.
"The ultimate goal is to take the understanding we gain at each step and put it into a cohesive, coordinated picture. Then we can think about designing a vaccine."