Immunization of Aotus monkeys with recombinant cysteine-rich interdomain region 1α protects against severe disease during Plasmodium falciparum reinfection

Background. After continuous exposure to malarial infections in regions of Africa where malaria is hyperendemic, children attain clinical immunity. This immunity results, in part, from the acquisition of antibodies against a large repertoire of variant antigens expressed on the surface of infected erythrocytes, such as the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). We determined whether a subunit vaccine to a portion of PfEMP1 could induce protection in nonhuman primates. Methods. We immunized Aotus nancymai monkeys with PfEMP1 recombinant (r) cysteine-rich interdomain region 1 alpha (CIDR1 alpha) and infected them twice with P. falciparum Vietnam Oak Knoll strain, the most virulent strain of P. falciparum in Aotus monkeys-each infection expressed a different PfEMP1. Anti-PfEMP1 antibodies were analyzed by enzyme-linked immunosorbent assay against rCIDR1 alpha and by flow cytometry against infected erythrocytes. Results. Immunization with rCIDR1a was not protective, despite delayed patency during the first infection, but it protected monkeys against severe anemia during reinfection. Protection against anemia is associated with a more rapid increase in antibodies to PfEMP1. Conclusion. The findings of reduced severe disease in rCIDR1 alpha-vaccinated Aotus monkeys provide experimental support for a PfEMP1-based vaccine to protect African children against severe malarial disease. Such vaccination may function by priming for the accelerated acquisition of immunity to new PfEMP1 variants.