Passive Immunization with Antibodies against Three Distinct Epitopes on Plasmodium yoelii Merozoite Surface Protein 1 Suppresses Parasitemia

Abstract

ABSTRACT 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 ∼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 ∼33-kDa polypeptide (MSP-1 33 ) and a C-terminal ∼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.