Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (Pf MSP1) of <i>Plasmodium falciparum</i> are associated with reduced malaria morbidity

Riley, Eleanor M.; Allen, Stephen; Wheeler, Jeremy G; Blackman, Michael J.; Bennett, Steve; Takács, B.; Schönfeld, H.; Holder, Anthony A.; Greenwood, Brian

doi:10.1111/j.1365-3024.1992.tb00471.x

Cited by 235 publications

(208 citation statements)

References 32 publications

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“…Genes encoding surface antigens targeted by the host's immune response are subject to diversifying selection promoting genetic polymorphism (44). There is evidence for diversifying selection acting on erythrocyte-binding antigens in P. vivax as well as P. falciparum (12).…”

Section: Discussionmentioning

confidence: 99%

Meager genetic variability of the human malaria agent Plasmodium vivax

Leclerc

Durand

Gauthier

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Malaria is a major human parasitic disease caused by four species of Plasmodium protozoa. Plasmodium vivax, the most widespread, affects millions of people across Africa, Asia, the Middle East, and Central and South America. We have studied the genetic variability of 13 microsatellite loci in 108 samples from 8 localities in Asia, Africa, South America, and New Guinea. Only one locus is polymorphic; nine are completely monomorphic, and the remaining three are monomorphic in all but one or two populations, which have a rare second allele. In contrast, Plasmodium falciparum displays extensive microsatellite polymorphism within and among populations. We further have analyzed, in 96 samples from the same 8 localities, 8 tandem repeats (TRs) located on a 100-kb contiguous chromosome segment described as highly polymorphic. Each locus exhibits 2-10 alleles in the whole sample but little intrapopulation polymorphism (1-5 alleles with a prevailing allele in most cases). Eight microsatellite loci monomorphic in P. vivax are polymorphic in three of five Plasmodium species related to P. vivax (two to seven individuals sampled). Plasmodium simium, a parasite of New World monkeys, is genetically indistinguishable from P. vivax. At 13 microsatellite loci and at 7 of the 8 TRs, both species share the same (or most common) allele. Scarce microsatellite polymorphism may reflect selective sweeps or population bottlenecks in recent evolutionary history of P. vivax; the differential variability of the TRs may reflect selective processes acting on particular regions of the genome. We infer that the world expansion of P. vivax as a human parasite occurred recently, perhaps <10,000 years ago.

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Section: Discussionmentioning

confidence: 99%

Meager genetic variability of the human malaria agent Plasmodium vivax

Leclerc

Durand

Gauthier

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…In the present study, a single microarray hybridization has added substantially to our list of candidate genes for testing as transmission blocking agents. It is noteworthy that MSP-1, a leading candidate for malaria vaccines (Holder, 1988;Riley et al, 1992), is one of the most prominent blood stage-speci®c transcripts identi®ed by microarray hybridization (Table 2A). Other transcripts from Table 2A may prove to be important new targets for asexual stage vaccines.…”

Section: Advantages Of the Shotgun Approachmentioning

confidence: 99%

Shotgun DNA microarrays and stage‐specific gene expression in Plasmodium falciparum malaria

Hayward

DeRisi

AlFadhli

et al. 2000

Molecular Microbiology

203

100

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SummaryMalaria infects over 200 million individuals and kills 2 million young children every year. Understanding the biology of malarial parasites will be facilitated by DNA microarray technology, which can track global changes in gene expression under different physiological conditions. However, genomes of Plasmodium sp. (and many other important pathogenic organisms) remain to be fully sequenced so, currently, it is not possible to construct gene-speci®c microarrays representing complete malarial genomes. In this study, 3648 random inserts from a Plasmodium falciparum mung bean nuclease genomic library were used to construct a shotgun DNA microarray. Through differential hybridization and sequencing of relevant clones, large differences in gene expression were identi®ed between the blood stage trophozoite form of the malarial parasite and the sexual stage gametocyte form. The present study lengthens our list of stage-speci®c transcripts in malaria by at least an order of magnitude above all previous studies combined. The results offer an unprecedented number of leads for developing transmission blocking agents and for developing vaccines directed at blood stage antigens. A signi®cant fraction of the stage-selective transcripts had no sequence homologues in the current genome data bases, thereby underscoring the importance of the shotgun approach. The malarial shotgun microarray will be useful for unravelling additional important aspects of malaria biology and the general approach may be applied to any organism, regardless of how much of its genome is sequenced.

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“…The antagonizing effects of MSP-1 variants were observed in the majority (average 80%) of individuals from The Gambia who showed IFN-c responses. T cell proliferation to MSP-1 recombinant proteins has been reported to correlate with protection against clinical malaria in prospective field studies [22]. Therefore, the observed correlation of both IFN-c and proliferative immune interference with allelic epitopes M3/4 and M7/8 could potentially affect protective memory T cell effector functions.…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies have shown that MSP-1 proliferative responses correlated with protection against clinical malaria [22]. Immune interference between allelic MSP-1 epitopes was further studied in assays of proliferation, set up in parallel with ex vivo IFN-c ELISPOT immune interference assays.…”

Section: Immune Interference Affects Both Proliferative T Cell Responmentioning

confidence: 99%

Dimorphic Plasmodium falciparum merozoite surface protein‐1 epitopes turn off memory T cells and interfere with T cell priming

et al. 2006

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The leading blood-stage malaria vaccine candidate antigen, Plasmodium falciparum merozoite surface protein-1 (MSP-1) occurs in two major allelic types worldwide. The molecular basis promoting this stable dimorphism is unknown. In this study, we have shown that allelic altered peptide ligand (APL) T cell epitopes of MSP-1 mutually inhibited IFN-c secretion as well as proliferation of CD4 + T cells in 27/34 malaria exposed Gambian volunteers. Besides this inhibition of malaria-specific immunity, the same variant epitopes were also able to impair the priming of human T cells in malaria naive individuals. Epitope variants capable of interfering with T cell priming as well as inhibiting memory T cell effector functions offer a uniquely potent combination for immune evasion. Indeed, enhanced co-habitation of parasites bearing such antagonistic allelic epitope regions was observed in a study of 321 West African children, indicating a survival advantage for parasites able to engage this inhibitory immune interference mechanism.

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Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (Pf MSP1) of Plasmodium falciparum are associated with reduced malaria morbidity

Cited by 235 publications

References 32 publications

Meager genetic variability of the human malaria agent Plasmodium vivax

Meager genetic variability of the human malaria agent Plasmodium vivax

Shotgun DNA microarrays and stage‐specific gene expression in Plasmodium falciparum malaria

Dimorphic Plasmodium falciparum merozoite surface protein‐1 epitopes turn off memory T cells and interfere with T cell priming

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