Plasmodium vivax: Dimorphic DNA Sequences from the MSP-1 Gene Code for Regions That Are Immunogenic in Natural Infections

Mancilla, Lida Inés; Levitus, Gabriela; Kirchgatter, Karin; Mertens, Frédéric; Herrera, Silvia; Portillo, Hernando A. del

doi:10.1006/expr.1994.1074

Cited by 24 publications

(17 citation statements)

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“…The variable blocks of PbMSP-1 exhibit less intra-species variation than MSP-1 from P. falciparum [13,[41][42][43], P. 6i6ax [31,44,45] or P. chabaudi [16,17]. A lower level of intra-species variability in P. berghei as compared to other rodent Plasmodium species was also observed using isozyme analysis [46].…”

Section: Discussionmentioning

confidence: 72%

“…It was previously noted that the inter-species conserved blocks of MSP-1 have either h-helical or i-sheet predicted structures and the variable regions have random coil conformations which are likely to be surface exposed [19]. Furthermore, studies on the antigenicity of MSP-1 also suggest that the variable blocks are exposed to the immune system [31,32]. Based upon these observations we propose a hypothetical structural model in which the conserved regions of MSP-1 form a core structural backbone and the polymorphic regions form flexible loops exposed on the protein's surface.…”

Section: Discussionmentioning

confidence: 99%

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The complete sequence of Plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability

Jennings

Toebe

Belkum

et al. 1998

Molecular and Biochemical Parasitology

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The complete gene for merozoite surface protein-1 (MSP-1) from Plasmodium berghei has been cloned and sequenced. Comparison of the P. berghei MSP-1 sequence with MSP-1 from other rodent parasites reveals five conserved domains interrupted by four variable blocks. These variable blocks exhibit no sequence homology but do have similar amino acid compositions. Primary proteolytic processing sites are located near the boundaries between the conserved domains and the variable blocks. Sequencing of the variable blocks from several P. berghei isolates shows that the predominant intra-species difference is in the number of tandem repeats. The inter-and intra-species differences suggest that the variable blocks are localized areas with relatively high levels of slipped-strand mispairing, unequal crossing-over, or other intragenic recombination activity. MSP-1 from P. berghei exhibits more repetitiveness than MSP-1 from other species suggesting that P. berghei experiences a higher intrinsic level of events producing variable numbers of tandem repeats or a lower level of events leading to the degeneration of tandem repeats.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

The complete sequence of Plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability

Jennings

Toebe

Belkum

et al. 1998

Molecular and Biochemical Parasitology

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“…9 For the P. vivax MSP-1 gene, the variable region between interspecies conserved blocks 5 and 6 has been used to genotype P. vivax isolates from many different geographic regions, where at least five types have been discovered. [10][11][12][13][14][15] These studies demonstrate the high levels of heterogeneity of P. vivax field populations.…”

Section: Introductionmentioning

confidence: 60%

Genetic Diversity and Multiple Infections of Plasmodium Vivax Malaria in Western Thailand

Cui

Mascorro

Fan

et al. 2003

The American Journal of Tropical Medicine and Hygiene

136

127

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Abstract. Using two polymorphic genetic markers, the merozoite surface protein-3␣ (MSP-3␣) and the circumsporozoite protein (CSP), we investigated the population diversity of Plasmodium vivax in Mae Sod, Thailand from April 2000 through June 2001. Genotyping the parasites isolated from 90 malaria patients attending two local clinics for the dimorphic CSP gene revealed that the majority of the parasites (77%) were the VK210 type. Genotyping the MSP3-␣ gene indicated that P. vivax populations exhibited an equally high level of polymorphism as those from Papua New Guinea, a hyperendemic region. Based on the length of polymerase chain reaction products, three major types of the MSP-3␣ locus were distinguished, with frequencies of 74.8%, 18.7%, and 6.5%, respectively. The 13 alleles distinguished by restriction fragment length polymorphism analysis did not show a significant seasonal variation in frequency. Genotyping the MSP-3␣ and CSP genes showed that 19.3% and 25.6% of the patients had multiple infections, respectively, and the combined rate was 35.6%. Comparisons of MSP-3␣ sequences from nine clones further confirmed the high level of genetic diversity of the parasite and also suggested that geographic isolation may exist. These results strongly indicate that P. vivax populations are highly diverse and multiple clonal infections are common in this malaria-hypoendemic region of Thailand.

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“…Block 2 is the longest stretch of variable sequence contained in ICB2-5, a recombinant antigen recently shown to be targeted by naturally acquired protective antibodies (25). The centrally located block 6 is the most polymorphic block of PvMSP-1 (27), but little is known about the variant specificity of naturally acquired antibodies to this domain (20). Although block 10 is the longest stretch of variable sequence in the C-terminal part of PvMSP-1 (Fig.…”

Section: Methodsmentioning

confidence: 99%

Antigenic Polymorphism and Naturally Acquired Antibodies to Plasmodium vivax Merozoite Surface Protein 1 in Rural Amazonians

Bastos¹,

Silva‐Nunes

Malafronte

et al. 2007

Clin Vaccine Immunol

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Merozoite surface protein 1 of Plasmodium vivax (PvMSP-1), a major target for malaria vaccine development, contains six highly polymorphic domains interspersed with conserved sequences. Although there is evidence that the sequence divergence in PvMSP-1 has been maintained over 5 million years by balanced selection exerted by the host's acquired immunity, the variant specificity of naturally acquired antibodies to PvMSP-1 remains poorly investigated. Here, we show that 15 recombinant proteins corresponding to PvMSP-1 variants commonly found in local parasites were poorly recognized by 376 noninfected subjects aged 5 to 90 years exposed to malaria in rural Amazonia; less than one-third of them had detectable immunoglobulin G (IgG) antibodies to at least one variant of blocks 2, 6, and 10 that were expressed, although 54.3% recognized the invariant 19-kDa C-terminal domain PvMSP-1 19 . Although the proportion of responders to PvMSP-1 variants increased substantially during subsequent acute P. vivax infections, the specificity of IgG antibodies did not necessarily match the PvMSP-1 variant(s) found in infecting parasites. We discuss the relative contribution of antigenic polymorphism, poor immunogenicity, and original antigenic sin (the skew in the specificity of antibodies elicited by exposure to new antigenic variants due to preexisting variant-specific responses) to the observed patterns of antibody recognition of PvMSP-1. We suggest that antibody responses to the repertoire of variable domains of PvMSP-1 to which subjects are continuously exposed are elicited only after several repeated infections and may require frequent boosting, with clear implications for the development of PvMSP-1-based subunit vaccines.

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Plasmodium vivax: Dimorphic DNA Sequences from the MSP-1 Gene Code for Regions That Are Immunogenic in Natural Infections

Cited by 24 publications

References 0 publications

The complete sequence of Plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability

The complete sequence of Plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability

Genetic Diversity and Multiple Infections of Plasmodium Vivax Malaria in Western Thailand

Antigenic Polymorphism and Naturally Acquired Antibodies to Plasmodium vivax Merozoite Surface Protein 1 in Rural Amazonians

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