scholarly journals Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein.

1994 ◽  
Vol 180 (1) ◽  
pp. 389-393 ◽  
Author(s):  
M J Blackman ◽  
T J Scott-Finnigan ◽  
S Shai ◽  
A A Holder
Keyword(s):  
Malaria Parasite ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Secondary Processing ◽  
Erythrocyte Invasion ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Protective Antibodies ◽  
Epidermal Growth ◽  
Membrane Bound

When merozoites of the malaria parasite Plasmodium falciparum are released from infected erythrocytes and invade new red cells, a component of a protein complex derived from the merozoite surface protein 1 (MSP-1) precursor undergoes a single proteolytic cleavage known as secondary processing. This releases the complex from the parasite surface, except for a small membrane-bound fragment consisting of two epidermal growth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes. We report that, a group of monoclonal antibodies specific for epitopes within the EGF-like domains, some interfere with secondary processing whereas others do not. Those that most effectively inhibit processing have previously been shown to prevent invasion. Other antibodies, some of which can block this inhibition, not only do not prevent invasion but are carried into the host cell bound to the merozoite surface. These observations unequivocally demonstrate that the binding of antibody to the COOH-terminal region of MSP-1 on the merozoite surface may not be sufficient to prevent erythrocyte invasion, and show that the interaction of different antibodies with adjacent epitopes within the EGF-like domains of MSP-1 can have distinct biochemical effects on the molecule. Inhibition of MSP-1 processing on merozoites may be a mechanism by which protective antibodies interrupt the asexual cycle of the malaria parasite.

Random mating in a natural population of the malaria parasite Plasmodium falciparum

Parasitology ◽  
1994 ◽  
Vol 109 (4) ◽  
pp. 413-421 ◽  
Author(s):  
H. A. Babiker ◽  
L. C. Ranford-Cartwright ◽  
D. Currie ◽  
J. D. Charlwood ◽  
P. Billingsley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Random Mating ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Blood Parasites ◽  
Chain Reaction ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Polymerase Chain

SUMMARYThe genetic structure of a population of the malaria parasite Plasmodium falciparum has been examined in a village in Tanzania. Seventeen alleles of the merozoite surface protein MSP-1 and 23 of MSP-2 were detected by the polymerase chain reaction (PCR) among the blood parasites of the inhabitants. Most infections contained mixtures of genetically distinct parasite clones. PCR was then used to examine individual P. falciparum oocysts, the products of fertilization events, in wild-caught mosquitoes. Forty-five out of 71 oocysts were heterozygous for one or both genes, showing that crossing between clones was taking place frequently, following uptake of mixtures of gametocytes by the mosquitoes. The frequency of heterozygous forms showed that random mating events probably occurred within mosquito bloodmeals between gametes belonging to different parasite clones.

scholarly journals Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum

2006 ◽  
Vol 74 (2) ◽  
pp. 1313-1322 ◽  
Author(s):  
Ute Woehlbier ◽  
Christian Epp ◽  
Christian W. Kauth ◽  
Rolf Lutz ◽  
Carole A. Long ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Merozoite Surface Protein 1 ◽  
Erythrocyte Invasion ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Parasite Multiplication ◽  
Parasite Replication

ABSTRACT The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria.

scholarly journals Suramin and Suramin Analogues Inhibit Merozoite Surface Protein-1 Secondary Processing and Erythrocyte Invasion by the Malaria ParasitePlasmodium falciparum

2003 ◽  
Vol 278 (48) ◽  
pp. 47670-47677 ◽  
Author(s):  
Suzanne L. Fleck ◽  
Berry Birdsall ◽  
Jeffrey Babon ◽  
Anton R. Dluzewski ◽  
Stephen R. Martin ◽  
...  
Keyword(s):  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Secondary Processing ◽  
Merozoite Surface Protein 1 ◽  
Erythrocyte Invasion

Inhibitory and blocking monoclonal antibody epitopes on merozoite surface protein 1 of the malaria parasite Plasmodium falciparum11Edited by J. A. Wells

2001 ◽  
Vol 307 (5) ◽  
pp. 1381-1394 ◽  
Author(s):  
Chairat Uthaipibull ◽  
Barbara Aufiero ◽  
Shabih E.H Syed ◽  
Brian Hansen ◽  
José A.Guevara Patiño ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Malaria Parasite ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Merozoite Surface Protein 1 ◽  
Parasite Plasmodium ◽  
Antibody Epitopes

Proteins on the surface of the malaria parasite and cell invasion

Parasitology ◽  
1994 ◽  
Vol 108 (S1) ◽  
pp. S5-S18 ◽  
Author(s):  
A. A. Holder
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Malaria Parasite ◽  
Surface Protein ◽  
Cell Types ◽  
Merozoite Surface Protein ◽  
Amino Acid Sequences ◽  
Specific Cell ◽  
Binding Studies ◽  
Erythrocyte Invasion

SUMMARYThe malaria parasite exists in an extracellular form at several stages in its life cycle. Within the vertebrate host, sporozoites and merozoites have to invade specific cell types. Proteins on the surface of the parasite or externalized from specialized organelles have been implicated as ligands for receptors on the host cell surface. Direct binding studies have identified parasite proteins that interact with the target cell surface. Examination of the deduced amino acid sequences has allowed the identification of primary structural motifs which may have roles in this process. On the sporozoite, the circum-sporozoite protein and sporozoite surface protein-2, a protein initially located within micronemes, have been found to contain an amino acid sequence thought to be involved in mediating recognition of sulphated polysaccharides on the surface of a liver cell. On the merozoite, merozoite surface protein-1 may be involved in the initial recognition of red blood cells; this protein undergoes a complex series of modifications in the time between its synthesis as a precursor molecule and successful erythrocyte invasion. Other merozoite proteins located at the apical end of the parasite have been identified as erythrocyte or reticulocyte binding proteins.

scholarly journals Antibodies that Inhibit Malaria Merozoite Surface Protein–1 Processing and Erythrocyte Invasion Are Blocked by Naturally Acquired Human Antibodies

1997 ◽  
Vol 186 (10) ◽  
pp. 1689-1699 ◽  
Author(s):  
José A. Guevara Patiño ◽  
Anthony A. Holder ◽  
Jana S. McBride ◽  
Michael J. Blackman
Keyword(s):  
Inhibitory Activity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Secondary Processing ◽  
Human Antibodies ◽  
Merozoite Surface Protein 1 ◽  
Erythrocyte Invasion ◽  
Endoproteolytic Cleavage ◽  
Inhibitory Antibodies ◽  
Blocking Antibodies

Merozoite surface protein–1 (MSP-1) of the human malaria parasite Plasmodium falciparum undergoes at least two endoproteolytic cleavage events during merozoite maturation and release, and erythrocyte invasion. We have previously demonstrated that mAbs which inhibit erythrocyte invasion and are specific for epitopes within a membrane-proximal, COOH-terminal domain of MSP-1 (MSP-119) prevent the critical secondary processing step which occurs on the surface of the extracellular merozoite at around the time of erythrocyte invasion. Certain other anti–MSP-119 mAbs, which themselves inhibit neither erythrocyte invasion nor MSP-1 secondary processing, block the processing-inhibitory activity of the first group of antibodies and are termed blocking antibodies. We have now directly quantitated antibody-mediated inhibition of MSP-1 secondary processing and invasion, and the effects on this of blocking antibodies. We show that blocking antibodies function by competing with the binding of processing-inhibitory antibodies to their epitopes on the merozoite. Polyclonal rabbit antibodies specific for certain MSP-1 sequences outside of MSP-119 also act as blocking antibodies. Most significantly, affinity-purified, naturally acquired human antibodies specific for epitopes within the NH2-terminal 83-kD domain of MSP-1 very effectively block the processing-inhibitory activity of the anti-MSP-119 mAb 12.8. The presence of these blocking antibodies also completely abrogates the inhibitory effect of mAb 12.8 on erythrocyte invasion by the parasite in vitro. Blocking antibodies therefore (a) are part of the human response to malarial infection; (b) can be induced by MSP-1 structures unrelated to the MSP-119 target of processing-inhibitory antibodies; and (c) have the potential to abolish protection mediated by anti–MSP-119 antibodies. Our results suggest that an effective MSP-119–based falciparum malaria vaccine should aim to induce an antibody response that prevents MSP-1 processing on the merozoite surface.

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