Malaria vaccine development based on merozoite surface proteins ofPlasmodium falciparum

Sequential Processing of Merozoite Surface Proteins during and after Erythrocyte Invasion by Plasmodium falciparum

“…A further understanding of the molecular basis of merozoite protein processing might reveal attractive targets for the development of antimalarial inhibitors, and several proteases that inhibit invasion have been reported in the literature (6,13). Furthermore, with merozoite surface proteins being the targets of vaccine development, clear characterization of individual proteins during and after invasion informs vaccine development by identifying periods when parasite proteins are most likely to be targeted by the immune system (32,33). In conclusion, these studies advance our understanding of the mechanisms of invasion, demonstrating that the loss of the merozoite surface coat is not a global event and instead involves specific processes resulting in the sequential cleavage of individual proteins both during and after invasion, indicating the diversity of roles of different proteins (Fig.…”

“…We aimed to investigate whether the shedding of the merozoite surface coat during invasion involves the specific processing of individual proteins, reflecting the different roles and functions of merozoite surface proteins during invasion rather than shedding being a nonspecific global process resulting in the complete loss of the merozoite surface protein coat. A detailed understanding of invasion is important because merozoite proteins are leading vaccine candidates (32)(33)(34), and targeting of invasion may be an effective strategy in antimalarial drug development (6,56). We show that loss of the merozoite surface coat is not a global event and instead involves specific processes resulting in the sequential cleavage of individual proteins both during and after invasion, indicating the diversity of roles of different proteins.…”

“…Merozoite surface proteins have long been considered attractive targets for malaria vaccine development, and several proteins have progressed to phase 1 and 2 clinical trials (32,33). Merozoite surface proteins also appear to be important targets of acquired human immunity, particularly antibodies (34)(35)(36)(37)(38).…”

Plasmodium falciparum Merozoite Surface Protein 3

“…Merozoite surface proteins of Plasmodium falciparum are regarded as suitable candidates for developing vaccine against malaria mainly because they are relatively more exposed to the host immune system during the erythrocytic stage of parasite development (2). Surface location also suggests the possible role of these proteins in the invasion of red cells; several of these are also being investigated for their potential as vaccine candidates and as mediators of invasion of erythrocytes (3).…”

“…Surface location also suggests the possible role of these proteins in the invasion of red cells; several of these are also being investigated for their potential as vaccine candidates and as mediators of invasion of erythrocytes (3). Some of the major surface proteins of P. falciparum like MSP1, MSP4, MSP5, MSP8, and MSP10 are displayed to the parasite membrane through a glycosylphosphatidylinositol (GPI) 5 anchor (2). Other surface proteins, including MSP3, MSP6, MSP7, and MSP9 (also known as ABRA), are soluble proteins and are present on the merozoite surface as a protein complex, possibly through protein-protein interactions (4).…”