Plasmodium falciparum merozoite surface protein 1 (MSP1): genotyping and humoral responses to allele-specific variants

Ekala, Marie-Thérèse; Jouin, H; Lékoulou, Faustin; Issifou, Saadou; Mercereau‐Puijalon, Odile; Ntoumi, Francine

doi:10.1016/s0001-706x(01)00188-7

Cited by 37 publications

(60 citation statements)

References 29 publications

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“…The results showed that some permutations of gain or loss of repeat motifs should influence the antigenicity. Other studies have also shown that antibodies react with diverse sequences in the K1-like repeats (10,18). Our aim was first to identify epitopes recognized by human antibodies and murine MAbs to the K1-like repeat sequences and then to design a minimal composite antigen sequence that would contain these epitopes.…”

Section: Discussionmentioning

confidence: 99%

Extensive Antigenic Polymorphism within the Repeat Sequence of thePlasmodium falciparumMerozoite Surface Protein 1 Block 2 Is Incorporated in a Minimal Polyvalent Immunogen

et al. 2005

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Polymorphism in pathogen antigens presents a complex challenge for vaccine design. A prime example is the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP1), to which allele-specific antibodies have been associated with protection from malaria. In a Zambian population studied here, 49 of 91 alleles sampled were of the K1-like type (the most common of three block 2 types in all African populations), and most of these had unique sequences due to variation in tri-and hexapeptide repetitive motifs. There were significant negative correlations between allelic sequence lengths of different regions of the repeats, so the complete repeat sequence had less length variation than its component parts, suggesting a constraint on overall length. Diverse epitopes recognized by three murine monoclonal antibodies and 24 individual human sera were then mapped by using a comprehensive panel of synthetic peptides, revealing epitopes in all regions of the repeats. To incorporate these different epitopes in a single molecule, a composite sequence of minimal overall length (78 amino acids) was then designed and expressed as a recombinant antigen. More human immune sera reacted with this "K1-like Super Repeat" antigen than with proteins consisting of single natural allelic sequences, and immunization of mice elicited antibodies that recognized a range of five cultured parasite lines with diverse K1-like MSP1 block 2 repeat sequences. Thus, complex allelic polymorphism was deconstructed and a minimal composite polyvalent antigen was engineered, delivering a designed candidate sequence for inclusion in a malaria vaccine.

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Section: Discussionmentioning

confidence: 99%

Extensive Antigenic Polymorphism within the Repeat Sequence of thePlasmodium falciparumMerozoite Surface Protein 1 Block 2 Is Incorporated in a Minimal Polyvalent Immunogen

et al. 2005

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“…The antibody responses to MSP2 peptides were assessed using a set of 15-mer synthetic peptides corresponding to blocks 1-3 of MSP2, including some variable sequences. To ensure homologous peptide presentation on ELISA plates, biotinylated peptides were used [11,12]. In order to assess the development of allelic family-specific humoral immune responses to MSP2, 25 Gabonese patients with symptomatic infections were followed-up one week after inclusion.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown, using 82 synthetic linear 15-mer peptides, overlapping on seven amino acids, which scanned a reference allele from each of the three allelic families of MSP1 gene and included a large array of sequence variants [11,12], the contribution of strain specific immunity to antiparasite immunity. An age-dependence in the recognition of the number of different MSP1 peptides by asymptomatic subjects was found with a particular increase after the age of 14 years [11].…”

Section: Introductionmentioning

confidence: 99%

“…An age-dependence in the recognition of the number of different MSP1 peptides by asymptomatic subjects was found with a particular increase after the age of 14 years [11]. Using MSP2 recombinant proteins most of the studies showed that IgG antibodies represented a good surrogate measure of protection and suggested that protective effects are due probably to …”

Section: Introductionmentioning

confidence: 99%

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Allelic family specific humoral responses to merozoite surface protein 2 (MSP2) in Gabonese residents with Plasmodium falciparum infections

Ekala¹

2002

Immunology Letters

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“…The high level of sequence conservation is in marked contrast to MSPs like MSP-1 and MSP-2 (7,8,10). In contrast, the rhoptry-associated protein 2 displays very limited sequence diversity (24).…”

Section: Discussionmentioning

confidence: 96%

Identification and Characterization of a Conserved, Stage-Specific Gene Product of Plasmodium falciparum Recognized by Parasite Growth Inhibitory Antibodies

et al. 2003

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We have identified a novel conserved protein of Plasmodium falciparum, designated D13, that is stagespecifically expressed in asexual blood stages of the parasite. The predicted open reading frame (ORF) D13 contains 863 amino acids with a calculated molecular mass of 99.7 kDa and displays a repeat region composed of pentapeptide motives. Northern blot analysis with lysates of synchronized blood stage parasites showed that D13 is highly expressed at the mRNA level during schizogony. The first N-terminal 138 amino acids of D13 were expressed in Escherichia coli and the purified protein was used to generate anti-D13 monoclonal antibodies (MAbs). Using total lysates of blood stage parasites and Western blot analysis, these MAbs stained one single band of ϳ100 kDa, corresponding to the predicted molecular mass of ORF D13. Western blot analysis demonstrated further that D13 is expressed during schizogony, declines rapidly in early ring stages and is undetectable in trophozoites. D13 protein is localized in individual merozoites in a distinct area, as demonstrated by indirect immunofluorescence analysis. After subcellular fractionation, D13 was confined to the pelleted fraction of the parasite lysate and its extraction by alkaline carbonate buffer treatment indicated that D13 is not a membrane-integral protein. Inclusion of certain anti-D13 MAbs into in vitro cultures of blood stage parasites resulted in considerable reduction in parasite growth. The N-terminal domain encompassing 158 amino acids is 94 and 95%, respectively, identical at the amino acid level between Plasmodium knowlesi, Plasmodium yoelii, and P. falciparum. In summary, we describe a novel stage-specifically expressed, highly conserved gene product of P. falciparum that is recognized by parasite growth inhibitory antibodies.

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Plasmodium falciparum merozoite surface protein 1 (MSP1): genotyping and humoral responses to allele-specific variants

Cited by 37 publications

References 29 publications

Extensive Antigenic Polymorphism within the Repeat Sequence of thePlasmodium falciparumMerozoite Surface Protein 1 Block 2 Is Incorporated in a Minimal Polyvalent Immunogen

Extensive Antigenic Polymorphism within the Repeat Sequence of thePlasmodium falciparumMerozoite Surface Protein 1 Block 2 Is Incorporated in a Minimal Polyvalent Immunogen

Allelic family specific humoral responses to merozoite surface protein 2 (MSP2) in Gabonese residents with Plasmodium falciparum infections

Identification and Characterization of a Conserved, Stage-Specific Gene Product of Plasmodium falciparum Recognized by Parasite Growth Inhibitory Antibodies

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