New antigens for malaria vaccine development and drug discovery
Unique antigenic domains of PfEMP1 a key parasite surface molecule implicated in development of severe malaria. Antibodies to these molecules stimulate cross strain immunity to both lab strains and clinical isolates of malaria parasites. These PfEMP1 molecules could be effective targets for new therapeutic strategies to treat or prevent severe malaria.
Targets for new anti-rosetting drugs for adjunctive therapies for severe malaria
Severe malaria is caused by infection with Plasmodium falciparum and, because it can rapidly progress and cause severe complications in multiple organs, can result in a medical emergency. There are an estimated 10 million cases per annum and approximately one million deaths. There is therefore an urgent need for effective interventions to prevent these symptoms occurring and to reduce mortality.
Severe malaria is linked to a process called rosetting in which malaria parasite-infected red blood cells form aggregates that block blood flow in vital organs. Researchers have identified regions in three key gene variants of a molecule PfEMP1, which is central to forming these rosettes. Antibodies to these PfEMP1 regions show reactivity to diverse laboratory strains and clinical isolates of the malaria parasite.
Optimised expression methods to permit production of antigens; In vivo evidence that targets are immunogenic, generate functional antibodies that block rosette formation and induce phagocytosis of infected red blood cells in vitro; Supportive data from clinical sera samples of children who do recover from malaria who have circulating antibodies to these PfEMP1 types.
- Stops adhesion of infected blood cells to blood vessels in major organs
- Approach is effective against multiple parasite strains and, therefore, broadly applicable
- Protect and treat infected individuals, blocking progress of the disease