Novel vaccines that both block and deceive blood stage malaria parasites

Each year, malaria afflicts more than 200 million people and tragically results in more than half a million deaths. Malaria has a complex life cycle where parasites enter the body via mosquito bite and set up a small infection in the liver. From the liver, the parasites spread into the blood stream where they amplify exponentially causing symptomatic disease. Current malaria vaccines target liver stage parasites and are only 30–40% effective in infants. Blood stage antigens should ideally be added to the vaccines to prevent breakthrough blood stage infections.

We have been working with blood stage vaccine researchers who are producing antibodies that interfere with the parasite’s ability to invade red blood cells (RBCs) by binding to parasite surface proteins. To understand what invasion steps the antibodies were active against, we microscopically imaged live invading parasites. As anticipated, we found that the antibodies appeared to prevent the parasites from strongly attaching to RBCs which they must do before invasion can commence. Unexpectedly, we found the antibodies neutralised parasites that had not invaded by changing them into amoebas that resemble intraerythrocytic forms of the parasite and are no longer invasion competent.

The aim of this project is to find out what proportion of the antibodies’ inhibitory activities are due to their direct blocking of invasion versus their parasite neutralisation activity to help inform future vaccine development.

Laboratory techniques learned will include tissue culturing, parasite growth experiments, assay development and live cell microscopy.