Identification of a potent combination of key Plasmodium falciparum merozoite antigens that elicit strain-transcending parasite-neutralizing antibodies.

摘要: Blood-stage malaria vaccines that target single Plasmodium falciparum antigens involved in erythrocyte invasion have not induced optimal protection field trials. vaccine development has faced two major hurdles, antigenic polymorphisms and molecular redundancy, which led to an inability demonstrate potent, strain-transcending, invasion-inhibitory antibodies. Vaccines multiple invasion-related parasite proteins may inhibit more efficiently. Our approach is develop a receptor-blocking blood-stage against P. targets the binding domains of adhesins, blocking their interaction with receptors thus inhibiting invasion. However, numerous ligands, challenge identify combinations elicit potent strain-transcending inhibition. We evaluated activities 20 different triple antibodies mixed vitro diverse set six key merozoite including novel ligands apical asparagine-rich protein (PfAARP), EBA-175 (PfF2), reticulocyte binding-like homologous 1 (PfRH1), PfRH2, PfRH4, thrombospondin (PTRAMP), are localized organelles translocated surface at time points during They bind erythrocytes specificities distinct pathways. The antibody combination PfAARP produced most efficacious inhibition clones. This antigen was selected for coimmunization as mixture balanced responses each inhibited demonstrated two-step screening elicits strong inhibition, supporting its vaccine.