Erythrocyte invasion profiles are associated with a common invasion ligand polymorphism in Senegalese isolates of<i>Plasmodium falciparum</i>

Lantos, Paul M.; Ahouidi, Ambroise D.; Bei, Amy K.; Jennings, Cameron V.; Sarr, Ousmane; Ndir, O.; Wirth, Dyann F.; Mboup, Souleymane; Duraisingh, Manoj T.

doi:10.1017/s0031182008005167

Cited by 27 publications

(33 citation statements)

References 37 publications

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“…Most clinical P. falciparum infections in these areas of West Africa contain a mixture of different parasite genotypes (35,36), so analysis of individual genotypes and replication of assays on parasite lines would require cloning and longer-term growth, with a potential for changes in phenotypes during culture adaptation. Slight differences in sampling dates between the countries over a 2-year period are unlikely to have caused variation here, as previous studies in The Gambia showed similar distributions of invasion phenotypes in population samples of mild clinical malaria isolates taken up to 6 years apart (20,21), and similar profiles have been seen in Senegal in successive years (25,26). It is possible that changes might be seen over longer periods if levels of endemicity and acquired immunity in particular populations are reduced by enhanced malaria treatment interventions.…”

Section: Discussionsupporting

confidence: 73%

“…It should be noted that this study involved comparisons of West African sites, and parasite populations are extensively connected in this large region of endemicity (35,39), so it is possible that parasites in other parts of the world might have different phenotypes, particularly in areas where there is little acquired immunity. However, the observed variation in each of the populations studied here covered most of the range seen in a nonstandardized comparison of data from different studies reported separately on more-diverse individual populations, including those from Asia and South America (17)(18)(19)(20)(21)(22)(23)(24)(25)(26). A vaccine based on known parasite ligands involved in invasion would need to incorporate a broad range of alternative EBA and Rh proteins in order to be effective for use in any local population, unless an effective vaccine can be based on a ligand such as Rh5 which appears to be consistently required for invasion (7).…”

Section: Discussionmentioning

confidence: 82%

“…This may be influenced by levels of endemicity, such that a low incidence of infection and minimal acquired immunity may allow many parasites to use a favored primary pathway, while a broader range of alternative invasion phenotypes may be selected for in areas of greater endemicity. Studies on clinical isolates have indicated a high diversity of invasion phenotypes in India (17), Brazil (18,19), Peru (19), Colombia (19), The Gambia (20,21), Kenya (22,23), Tanzania (24), and Senegal (25,26). However, apart from a small number of isolates from Peru and Colombia that were cultured together in a single laboratory (19), all other samples from each country were analyzed in different laboratories at different times, using a variety of assay protocols.…”

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confidence: 99%

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Variation in Plasmodium falciparum Erythrocyte Invasion Phenotypes and Merozoite Ligand Gene Expression across Different Populations in Areas of Malaria Endemicity

et al. 2015

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dPlasmodium falciparum merozoites use diverse alternative erythrocyte receptors for invasion and variably express cognate ligands encoded by the erythrocyte binding antigen (eba) and reticulocyte binding-like homologue (Rh) gene families. Previous analyses conducted on parasites from single populations in areas of endemicity revealed a wide spectrum of invasion phenotypes and expression profiles, although comparisons across studies have been limited by the use of different protocols. For direct comparisons within and among populations, clinical isolates from three different West African sites of endemicity (in Ghana, Guinea, and Senegal) were cryopreserved and cultured ex vivo after thawing in a single laboratory to assay invasion of target erythrocytes pretreated with enzymes affecting receptor subsets. Complete invasion assay data from 67 isolates showed no differences among the populations in the broad range of phenotypes measured by neuraminidase treatment (overall mean, 40.6% inhibition) or trypsin treatment (overall mean, 83.3% inhibition). The effects of chymotrypsin treatment (overall mean, 79.2% inhibition) showed heterogeneity across populations (Kruskall-Wallis P ‫؍‬ 0.023), although the full phenotypic range was seen in each. Schizont-stage transcript data for a panel of 8 invasion ligand genes (eba175, eba140, eba181, Rh1, Rh2a, Rh2b, Rh4, and Rh5) were obtained for 37 isolates, showing similar ranges of variation in each population except that eba175 levels tended to be higher in parasites from Ghana than in those from Senegal (whereas levels of eba181 and Rh2b were lower in parasites from Ghana). The broad diversity in invasion phenotypes and gene expression seen within each local population, with minimal differences among them, is consistent with a hypothesis of immune selection maintaining parasite variation.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 99%

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Variation in Plasmodium falciparum Erythrocyte Invasion Phenotypes and Merozoite Ligand Gene Expression across Different Populations in Areas of Malaria Endemicity

et al. 2015

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“…We observed variation in invasion pathways for ex vivo P. falciparum isolates from Thies, as we have previously reported (34,35) (Fig. 4A).…”

Section: Fig 2 Receptor Restriction Increases Inhibition Of Eba-175-esupporting

confidence: 81%

Inhibitory Humoral Responses to the Plasmodium falciparum Vaccine Candidate EBA-175 Are Independent of the Erythrocyte Invasion Pathway

Badiane

Bei

Ahouidi

et al. 2013

Clin Vaccine Immunol

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dPlasmodium falciparum utilizes multiple ligand-receptor interactions for invasion. The invasion ligand EBA-175 is being developed as a major blood-stage vaccine candidate. EBA-175 mediates parasite invasion of host erythrocytes in a sialic acid-dependent manner through its binding to the erythrocyte receptor glycophorin A. In this study, we addressed the ability of naturally acquired human antibodies against the EBA-175 RII erythrocyte-binding domain to inhibit parasite invasion of ex vivo isolates, in relationship to the sialic acid dependence of these parasites. We have determined the presence of antibodies to the EBA-175 RII domain by enzyme-linked immunosorbent assay (ELISA) in individuals from areas of Senegal where malaria is endemic with high and low transmission. Using affinity-purified human antibodies to the EBA-175 RII domain from pooled patient plasma, we have measured the invasion pathway as well as the invasion inhibition of clinical isolates from Senegalese patients in ex vivo assays. Our results suggest that naturally acquired anti-EBA-175 RII antibodies significantly inhibit invasion of Senegalese parasites and that these responses can be significantly enhanced through limiting other ligand-receptor interactions. However, the extent of this functional inhibition by EBA-175 antibodies is not associated with the sialic acid dependence of the parasite strain, suggesting that erythrocyte invasion pathway usage by parasite strains is not driven by antibodies targeting the EBA-175/glycophorin A interaction. This work has implications for vaccine design based on the RII domain of EBA-175 in the context of alternative invasion pathways.

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“…For PMR calculations in which Nm/T/Chymo treated parasitized donor cells are mixed 50:50 (v/v) with acceptor cells, multiplying by a factor of 2 accounts for the fact that only ½ of the cells in the well can be invaded [ 16 ]. If PMR is calculated using a non-enzyme treated culture (for example, if parasitized erythrocytes are directly cultured and parasitemia is measured at each reinvasion cycle) the factor of 2 is not used.…”

Section: Measuring In Vitro Invasion Inhibition By Antibodiesmentioning

confidence: 99%

Measuring Plasmodium falciparum Erythrocyte Invasion Phenotypes Using Flow Cytometry

Bei

Duraisingh

2015

Methods in Molecular Biology

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Having the ability to rapidly, accurately, and robustly measure Plasmodium falciparum merozoite invasion is a critical component in effective assessment of a blood stage vaccine's mechanism of action. Being able to measure invasion of erythrocytes accurately, objectively and in a high throughput fashion is of critical importance. Here, we describe a simple and robust flow cytometry method that allows for the measurement of the key invasion parameters of parasite multiplication rate and erythrocyte selectivity-both important determinants of disease severity-from the schizont to the ring stage of the parasite's life-cycle, thus separating invasion from growth of the parasite. Importantly, this method is able to accurately detect low levels of parasitemia and heterogeneity within the population that can be missed by enzymatic methods. Lastly, this method has been successfully adapted and employed in field based research settings for parasitemia measurements in vivo, ex vivo, and in vitro and to measure invasion inhibition by antibodies and the use of alternative pathways for invasion.

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Erythrocyte invasion profiles are associated with a common invasion ligand polymorphism in Senegalese isolates ofPlasmodium falciparum

Cited by 27 publications

References 37 publications

Variation in Plasmodium falciparum Erythrocyte Invasion Phenotypes and Merozoite Ligand Gene Expression across Different Populations in Areas of Malaria Endemicity

Variation in Plasmodium falciparum Erythrocyte Invasion Phenotypes and Merozoite Ligand Gene Expression across Different Populations in Areas of Malaria Endemicity

Inhibitory Humoral Responses to the Plasmodium falciparum Vaccine Candidate EBA-175 Are Independent of the Erythrocyte Invasion Pathway

Measuring Plasmodium falciparum Erythrocyte Invasion Phenotypes Using Flow Cytometry

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