Structural diversity in the 45-kilodalton merozoite surface antigen of Plasmodium falciparum

Smythe, Jason A.; Peterson, M G; Coppel, Ross L.; Saul, Allan; Kemp, David J.; Anders, Robin F.

doi:10.1016/0166-6851(90)90061-p

Cited by 172 publications

(119 citation statements)

References 18 publications

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“…When these alleles were grouped into 2 allelic families according to the dimorphic structure of the central variable region (SMYTHE et al, 1990), 24 alleles belonged to the FC27 family of alleles and 26 to the 3D7 family. Gene frequencies were calculated for genotypes deriving from the paired community samples.…”

Section: Samplingmentioning

confidence: 99%

6. Multiple Plasmodium falciparum infections in Tanzanian infants

Felger

Smith

Edoh

et al. 1999

Transactions of the Royal Society of Tropical Medicine and Hygi

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Paired blood samples from 99Tanzanian infants were analysed to examine the infection dynamics of Plasmedium falciparum during the first year of life. Infecting parasites were genotyped by polymerase chain reaction amplification of the polymorphic gene for the merozoite surface protein 2 and subsequent analysis according to the resulting restriction fragment length polymorphism pattern. The same samples served as controls in a parallel case-control study for which an additional blood sample was taken from each child during a fever episode. The relationship of the number of concurrent infections (multiplicity) with age and morbidity was analysed and results were compared to those of a similar study on older children between 2 and 7 years of age, carried out in the same village at the same time. The mean of 2 infecting genotypes per positive blood sample from community surveys was low compared to that in older children, and there was no significant age-dependency of multiplicity within the first year of life. Multiplicity of infection in fever cases was also independent of age. In infants, multiplicity was positively associated with parasite density and risk of clinical malaria, in contrast to the situation in older children (>2 years). The findings help in the understanding of infection dynamics, premunition, and development of semi-immunity in malaria.

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Section: Samplingmentioning

confidence: 99%

6. Multiple Plasmodium falciparum infections in Tanzanian infants

Felger

Smith

Edoh

et al. 1999

Transactions of the Royal Society of Tropical Medicine and Hygi

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“…With regard to mspl, such repeats occur in a region denoted 'block 2', and alleles can be further differentiated into 3 groups by sequence variations denoted Kl-, MAD20-and R033-types (KIMURA et al, 1990). msp2 alleles are classified similarly into 2 sequence groups denoted FC27-and ICI 3D7-types as well as by length polymorphisms (SMYTHE et al, 1990). For glurp, no allelic groups based on sequence have been identified, alleles being differentiated by size polymorphisms alone (BORRE et al,199 1).…”

Section: Introductionmentioning

confidence: 99%

Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study

Färnert

Arez

Babiker

et al. 2001

Transactions of the Royal Society of Tropical Medicine and Hygi

118

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Genetic diversity of malaria parasites represents a major issue in understanding several aspects of malaria infection and disease. Genotyping of Plasmodium falciparum infections with polymerase chain reaction @'CR)-based methods has therefore been introduced in epidemiological studies. Polymorphic regions of the mspl, msp2 and gluT genes are the most frequently used markers for genotyping, but methods may differ. A multicentre study was therefore conducted to evaluate the comparability of results from different laboratories when the same samples were analysed. Analyses of laboratory-cloned lines revealed high specificity but varying sensitivity. Detection of low-density clones was hampered in multiclonal infections. Analyses of isolates from Tanzania and Papua New Guinea revealed similar positivity rates with the same allelic types identified. The number of alleles detected per isolate, however, varied systematically between the laboratories especially at high parasite densities. When the analyses were repeated within the laboratories, high agreement was found in getting positive or negative results but with a random variation in the number of alleles detected. The msp2 locus appeared to be the most informative single marker for analyses of multiplicity of infection. Genotyping by PCR is a powerful tool for studies on genetic diversity of I? falciparum but this study has revealed limitations in comparing results on multiplicity of infection derived from different laboratories and emphasizes the need for highly standardized laboratory protocols.

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“…But whether protection is associated with AMA-1-specific responses remains to be shown. The extensive polymorphisms of current candidate Ags is deemed to be a major hurdle for blood-stage vaccine development (37)(38)(39)(40)(41). Hence, although a couple of bloodstage Ags are under vaccine development, it is possible to search for more vaccine candidates.…”

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confidence: 99%

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

Dreyer

Matile

Papastogiannidis

et al. 2012

The Journal of Immunology

114

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An effective malaria vaccine could prove to be the most cost-effective and efficacious means of preventing severe disease and death from malaria. In an endeavor to identify novel vaccine targets, we tested predicted Plasmodium falciparum open reading frames for proteins that elicit parasite-inhibitory Abs. This has led to the identification of the cysteine-rich protective Ag (CyRPA). CyRPA is a cysteine-rich protein harboring a predicted signal sequence. The stage-specific expression of CyRPA in late schizonts resembles that of proteins known to be involved in merozoite invasion. Immunofluorescence staining localized CyRPA at the apex of merozoites. The entire protein is conserved as shown by sequencing of the CyRPA encoding gene from a diverse range of P. falciparum isolates. CyRPA-specific mAbs substantially inhibited parasite growth in vitro as well as in a P. falciparum animal model based on NOD-scid IL2Rγnull mice engrafted with human erythrocytes. In contrast to other P. falciparum mouse models, this system generated very consistent results and evinced a dose-response relationship and therefore represents an unprecedented in vivo model for quantitative comparison of the functional potencies of malaria-specific Abs. Our data suggest a role for CyRPA in erythrocyte invasion by the merozoite. Inhibition of merozoite invasion by CyRPA-specific mAbs in vitro and in vivo renders this protein a promising malaria asexual blood-stage vaccine candidate Ag.

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Structural diversity in the 45-kilodalton merozoite surface antigen of Plasmodium falciparum

Cited by 172 publications

References 18 publications

6. Multiple Plasmodium falciparum infections in Tanzanian infants

6. Multiple Plasmodium falciparum infections in Tanzanian infants

Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

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