Invasion of erythrocytes and the cycles of growth of blood stage parasites are central features of the virulence and pathogenicity of Plasmodium falciparum. A vaccine that targets the replicating blood stage parasites is a key strategy in alleviating the global burden of malaria.
Merozoites, the parasite forms that invade erythrocytes, are extracellular for a short time between egress from the spent host cell and invasion of the new host cell. This stage is an Achilles heel in parasite development since there is direct exposure to the host immune system for a short time. A significant problem in targeting merozoite surface antigens by vaccination is the high level of genetic diversity, making neutralizing immune responses very strain-specific.
An alternative approach to choosing appropriate antigens for vaccine development is to try to target essential processes in invasion that are mediated by proteins that are less polymorphic. P. falciparum has evolved a complex series of alternative erythrocyte invasion pathways mediated by multiple ligands expressed at the point of merozoite-erythrocyte contact.
We have raised antibodies to several invasion ligands to assess their suitability for development as an invasion-blocking vaccine.
We are investigating whether antibodies targeting multiple invasion ligands can overcome the plasticity of Pf invasion, inhibiting a wide spectrum of parasite invasion pathways.