– including some of the researchers involved in the 2012 work – used a technique called X-ray crystallography to investigate the three-dimensional structure of the CyRPA protein. However, efforts to develop a highly effective vaccine against malaria have so far been unsuccessful.įavuzza et al. If the microbe later enters the body, these antibodies can be produced quickly to eliminate the microbe before it causes disease. Vaccines help the body to recognise and fight an invading microbe by triggering an immune response that results in the production of proteins called antibodies, which can bind to specific molecules on the surface of the microbe.
In 2012, a team of researchers discovered that a protein called CyRPA forms a group (or ‘complex’) with several other proteins to allow the parasites to enter red blood cells.ĭeveloping a vaccine is one of the most promising approaches to prevent malaria. This includes a stage where the parasites infect the mammal’s red blood cells, which causes the symptoms of the disease. Plasmodium parasites have a complex life cycle involving both mosquito and mammal hosts. Microscopic parasites known as Plasmodium are responsible for causing this disease. About 200 million people are infected every year, placing a huge social and medical burden especially on developing countries. Malaria is one of the deadliest infectious diseases worldwide, killing over 400,000 people a year. Both in vitro and in vivo anti-PfCyRPA and anti-PfRH5 antibodies showed more potent parasite growth inhibitory activity in combination than on their own, supporting a combined delivery of PfCyRPA and PfRH5 in vaccines. Characterization of the epitope recognized by protective antibodies may facilitate design of peptidomimetics to focus vaccine responses on protective epitopes.
PfCyRPA adopts a 6-bladed β-propeller structure with similarity to the classic sialidase fold, but it has no sialidase activity and fulfills a purely non-enzymatic function. Here, we present the crystal structures of PfCyRPA and its complex with the antigen-binding fragment of a parasite growth inhibitory antibody. Among them, the Plasmodium falciparum Cysteine-Rich Protective Antigen (PfCyRPA) is a crucial component of a ternary complex, including Reticulocyte binding-like Homologous protein 5 (PfRH5) and the RH5-interacting protein (PfRipr), essential for erythrocyte invasion. Invasion of erythrocytes by Plasmodial merozoites is a composite process involving the interplay of several proteins.
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