Action of Malarial Antibody in vitro

Cohen, S.; Butcher, G. A.; Crandall, Richard B.

doi:10.1038/223368a0

Cited by 134 publications

(72 citation statements)

References 11 publications

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“…3), in contrast to the rising parasitemia observed in intact and splenectomized nonimmune rats. Antiplasmodial defense in immune rats is incompletely understood but may depend upon antibody-mediated inhibition of merozoite invasion (36,40). These findings suggest that different mechanisms of host defense might be important in resolution of acute primary infections and resistance to rechallenge in immune rats.…”

Section: Discussionmentioning

confidence: 95%

Intravascular Clearance of Parasitized Erythrocytes in Rodent Malaria

Quinn

Wyler

1979

J. Clin. Invest.

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A B ST RA CT Little is known about host defense mechanisms responsible for protective immunity in malaria. The intravascular location of the infection suggested that removal of parasitized erythrocytes by reticuloendothelial organs might be important. To study this possibility, we examined the clearance of 51Cr-labeled Plasmodiumn berghei-infected erythrocytes in rats. Infected erythrocytes were removed more rapidly from circulation than homologous uninfected erythrocytes. The rate of clearance of infected cells during the 1st hour after inoculation was approximately three times greater in rats rendered immune by prior infection than in control rats. This accelerated clearance resulted from greater splenic uptake in immune rats and appeared to correlate with spleen size. Since the clearance pattern of infected erythrocytes more closely resembled the clearance of Heinz body-containing uninfected erythrocytes than of antibody-coated (immunoglobulin G) uninfected erythrocytes, rheologic alterations of parasitized erythrocytes might be a more important determinant of clearance than an anitibodydependent process. During the phase of malaria infection in which increasing parasitemia is observed, organ uptake of infected erythrocytes did not increase despite splenic and hepatic enlargement. However during the spontaneous onset of resolution of malaria infection characterized by decreasing parasitemia, a marked enhancement of splenic clearance was noted. These observations suggest that sudden alteration in splenic clearance of parasitized erythrocytes might be important in the resolution of acute malaria.

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Section: Discussionmentioning

confidence: 95%

Intravascular Clearance of Parasitized Erythrocytes in Rodent Malaria

Quinn

Wyler

1979

J. Clin. Invest.

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“…Since sera from studies in regions of malaria endemicity are usually from children, the total volumes available are typically very small and it is preferable to reduce the amounts needed for each assay, particularly if multiple assays are to be performed. In our assays, we used 2.5 l of patient serum per well, which is significantly less than what has been used in other assays (6,8,17,20). Since the variation between duplicate samples in our optimized assay is very small, there is a reduced need for replicate samples and retesting, which further reduces the amount of sample required.…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies that inhibit the invasion of red blood cells by the merozoite form of the parasite are thought to be an important component of protective immunity by limiting parasite bloodstage growth in vivo (6,8), thereby reducing total parasite biomass and organ-specific sequestration that contribute to disease pathogenesis. Monoclonal and polyclonal antibodies against several merozoite antigens generated by vaccination in animals inhibit invasion (7,19,26) and may confer protection in animal models (11,23).…”

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confidence: 99%

Development and Optimization of High-Throughput Methods To MeasurePlasmodium falciparum-Specific Growth Inhibitory Antibodies

et al. 2006

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Antibodies that inhibit replication of Plasmodium falciparum in erythrocytes are thought to be important both in acquired immunity to malaria and as mediators of immunity generated by candidate blood-stage vaccines. However, several constraints have limited the study of these functional antibodies in population studies and vaccine trials. We report the development and optimization of high-throughput growth inhibition assays with improved sensitivity that use minimal volumes of test serum. The major inhibitory activity of serum from exposed donors was antibody mediated, but nonspecific inhibitory factors were found in untreated serum. Culture volumes could be effectively reduced to 25 l to limit amounts of test serum or inhibitors used in assays. Performing inhibition assays over two cycles of parasite replication gave greater sensitivity than single-cycle assays, and a simple two-cycle inhibition assay was developed that yielded highly reproducible results. Determination of parasite growth by flow cytometry was most suitable for high-throughput assays using small culture volumes and was more sensitive than parasite lactate dehydrogenase assays and less prone to error and variation than microscopy. We evaluated and optimized methods to remove antimalarials and nonspecific inhibitory factors from serum that are suitable for use with small volumes of samples that are typically obtained from clinical studies. Both microdialysis and immunoglobulin purification by ammonium sulfate precipitation were effective and practical. These methods should facilitate evaluation of vaccine trials and clinical studies of immunity and are also suitable for testing drugs and other compounds for antimalarial activity.

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“…Antibodies are believed to be an important component of acquired protective immunity, in addition to other factors (2). During blood-stage replication, P. falciparum merozoites invade erythrocytes, and antibodies that inhibit invasion and subsequent replication are believed to be important in mediating both acquired immunity and immunity generated by candidate blood-stage vaccines (3)(4)(5). However, the targets of acquired inhibitory antibodies are largely undefined.…”

Section: Introductionmentioning

confidence: 99%

Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies

Persson¹,

McCallum²,

Reiling³

et al. 2008

J. Clin. Invest.

170

228

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Antibodies that inhibit Plasmodium falciparum invasion of erythrocytes are believed to be an important component of immunity against malaria. During blood-stage infection, P. falciparum can use different pathways for erythrocyte invasion by varying the expression and/or utilization of members of 2 invasion ligand families: the erythrocyte-binding antigens (EBAs) and reticulocyte-binding homologs (PfRhs). Invasion pathways can be broadly classified into 2 groups based on the use of sialic acid (SA) on the erythrocyte surface by parasite ligands. We found that inhibitory antibodies are acquired by malaria-exposed Kenyan children and adults against ligands of SA-dependent and SA-independent invasion pathways, and the ability of antibodies to inhibit erythrocyte invasion depended on the pathway used by P. falciparum isolates. Differential inhibition of P. falciparum lines that varied in their use of specific EBA and PfRh proteins pointed to these ligand families as major targets of inhibitory antibodies. Antibodies against recombinant EBA and PfRh proteins were acquired in an age-associated manner, and inhibitory antibodies against EBA175 appeared prominent among some individuals. These findings suggest that variation in invasion phenotype might have evolved as a mechanism that facilitates immune evasion by P. falciparum and that a broad inhibitory response against multiple ligands may be required for effective immunity.

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Action of Malarial Antibody in vitro

Cited by 134 publications

References 11 publications

Intravascular Clearance of Parasitized Erythrocytes in Rodent Malaria

Intravascular Clearance of Parasitized Erythrocytes in Rodent Malaria

Development and Optimization of High-Throughput Methods To MeasurePlasmodium falciparum-Specific Growth Inhibitory Antibodies

Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies

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