Passive immunization with antibodies against three distinct epitopes on Plasmodium yoelii merozoite surface protein 1 suppresses parasitemia

We have produced monoclonal antibodies against Plasmodium yoelii merozoite surface protein 1 (MSP-1) and have assessed their ability to suppress blood stage parasitemia by passive immunization. Six immunoglobulin G antibodies were characterized in detail: three (B6, D3, and F5) were effective in suppressing a lethal blood stage challenge infection, two (B10 and G3) were partially effective, and one (B4) was ineffective. MSP-1 is the precursor to a complex of polypeptides on the merozoite surface; all of the antibodies bound to this precursor and to an similar to 42-kDa fragment (MSP-1(42)) that is derived from the C terminus of MSP-1. MSP-1(42) is further cleaved to an N-terminal similar to 33-kDa polypeptide (MSP-1(33)) and a C-terminal similar to 19-kDa polypeptide (MSP-1(19)) comprised of two epidermal growth factor (EGF)-like modules. D3 reacted with MSP-1(42) but not with either of the constituents MSP-1(33) and MSP-1(19), B4 recognized an epitope within the N terminus of MSP-1(33), and B6, B10, F5, and G3 bound to MSP-1(19). B10 and G3 bound to epitopes that required both C-terminal EGF-like modules for their formation, whereas B6 and F5 bound to epitopes in the first EGF-like module. These results indicate that at least three distinct epitopes on P. yoelii MSP-1 are recognized by antibodies that suppress parasitemia in vivo.