Faster, Stronger Immunity

The human immune response to malaria is slow and inefficient. The hope is that we can make a vaccine that does better than nature. A mosquito bite injects parasites that make for the liver, where they invade its cells. At this stage, the infection is very vulnerable, the numbers of parasites are small, and they can be killed by immune cells called CD8+ T cells. These remarkable cells—which are capable of specifically finding and killing parasite-infected cells—are the focus of my research.

In a normal infection the immune system sends T cells to kill the parasite in the liver—but this natural response is too little, too late. But a vaccine could ensure that enough T cells are in place beforehand to prevent infection from getting established.

So, how do you make enough malaria-specific T cells? We know that if you infect people with irradiated parasites they are protected. People become immune because the irradiated parasites can’t divide, which makes them harmless, but they still manage to induce a good immune response. Immunizing many people with irradiated parasites would be logistically very challenging so it may not be a realistic vaccine, but it gives us clues to how to make one. One thing we’ve found is that even after the irradiated parasite is long gone, the immune system still holds onto proteins from the parasite, stimulating the immune system for months. This helps to generate a robust T cell response. Clearly this would be a good property to engineer into any vaccine we make down the line.

There are a number of promising vaccines under development. They can be made even better as we learn more about the human immune response to malaria.