Vaccine development for blood-stage malaria
Each year, over 200 million people worldwide contract malaria. The malaria pathogens, called plasmodia, are transmitted by mosquitoes and pass through different stages of development in the liver and red blood cells. Humans develop immunity against the disease after having been routinely exposed to the disease. This immunity is characterised by a mitigation of symptoms over the course of a renewed infection. This project examines the immune responses that occur during controlled malaria infection in healthy adult volunteers from Gabon. As malaria is highly endemic in Gabon, all volunteers have been exposed to the malaria pathogen since their early childhood. The aim is to develop a novel vaccine against blood-stage malaria based on these new findings.
Malaria is a challenging infectious disease for the global population. Natural immunity is acquired by repeated infection and is characterised by a mitigation of symptoms and a lower frequency of disease episodes. Sterile immunity, which provides complete protection, can now be created experimentally in humans by means of a vaccination schedule developed in Tübingen. Naturally developed immunity targets blood-stage malaria, which occurs after the parasites have completed a cycle of development in the liver cells and entered the blood stream. Symptoms and complications of malaria occur during the blood stage.
A particularly effective vaccine against malaria infection in humans was developed at the DZIF in Tübingen. It is termed PfSPZ CVac and targets the parasites before they enter the blood stream. This vaccine project now aims to expand the vaccine’s range of immunity by adding a component that imitates naturally acquired immunity. Consequently, it will also target parasites in the blood which are already at a reproductive stage.
With this project we aim to investigate the actual immune system mechanisms involved in the development of immune protection and to what degree they can be used for developing vaccine candidates. We are consequently collaborating with our African Partner Institution in Lambaréné, Gabon. In a clinical trial, we induce controlled malaria infections in healthy adult volunteers who have been exposed to malaria pathogens since childhood and consequently developed natural immunity, and subsequently measure the immune responses. We then investigate which parasite antigens are targeted by human antibodies. We use systematic investigations and statistical models to identify candidates for subsequent further efficacy testing.
