Differential antibody recognition of FC27‐like <i>Plasmodium falciparum</i> merozoite surface protein MSP2 antigens which lack 12 amino acid repeats

Ranford-Cartwright, Lisa; Taylor, Ryan W.; Asgari-Jirhandeh, Nima; Smith, Donald B.; Roberts, P. A.; Robinson, Valerie; Babiker, Hamza A.; Riley, Eleanor M.; Walliker, David; McBride, Jana S.

doi:10.1046/j.1365-3024.1996.d01-137.x

Cited by 33 publications

(30 citation statements)

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“…The major serological subdivision of the FC27-like alleles was between those that contain multiple 32-mer repeats and single (or no) 12-mer repeats (groups 1 and 2 in Table 2) and those that contain a single 32-mer repeat and multiple 12-mer repeats (group 3). Within group 3, differences in the number of 12-mer repeats seriously affected the avidity of antibody binding, confirming our previous observations (27) These data provide evidence in support of the immune selection hypothesis for the FC27 family of msp-2 alleles. However, the number of "strains" or serogroups appears to be rather limited (perhaps as few as 2 or 3), with each serogroup comprising multiple cross-reactive variants.…”

Section: Discussionsupporting

confidence: 90%

“…The 32-mer and 12-mer repeats vary in number (12-mer repeats being completely absent in some sequences), and minor sequence differences occur within the repeats (Table 2). The number of 12-mer repeats can affect the avidity of antibody binding (27). All alleles shown in Table 2 share a conserved 12-aa sequence (ESSSSGNAPNKT) at the C terminus and a conserved 7-aa sequence (ADTPTAT) between the 32-mer and 12-mer repeats.…”

Section: Resultsmentioning

confidence: 99%

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Genetic Diversity and Antigenic Polymorphism in Plasmodium falciparum : Extensive Serological Cross-Reactivity between Allelic Variants of Merozoite Surface Protein 2

et al. 2003

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Diversity in the surface antigens of malaria parasites is generally assumed to be a mechanism for immune evasion, but there is little direct evidence that this leads to evasion of protective immunity. Here we show that alleles of the highly polymorphic merozoite surface protein 2 (MSP-2) can be grouped (within the known dimorphic families) into distinct serogroups; variants within a serogroup show extensive serological crossreactivity. Cross-reactive epitopes are immunodominant, and responses to them may be boosted at the expense of responses to novel epitopes (original antigenic sin). The data imply that immune selection explains only some of the diversity in the msp-2 gene and that MSP-2 vaccines may need to include only a subset of the known variants in order to induce pan-reactive antibodies.Allelic diversity in malaria parasites is widely assumed to be a mechanism for immune evasion (7,24). Among surface proteins, diversity arises from multiple point mutations or variations in the numbers, lengths, and sequences of amino acid repeats. Repeat diversity may arise from intragenic recombination, misalignment of repeated DNA sequences (6), or complementary-strand slippage (12, 13) during DNA replication. The AT-rich nature of the Plasmodium falciparum genome may facilitate the generation of new variants (28). The maintenance of variants in the population implies that they have a selective advantage (e.g., evasion of preexisting immune responses) or that the mutations are selectively neutral and that population diversification occurs randomly.In some genes (e.g., the circumsporozoite surface protein [csp] gene), point mutations cluster in areas immunodominant for T cells (16) and can lead to loss of epitope recognition (38) or antagonism of T-cell responses (26), although it is not clear that either of these leads to the avoidance of protective immunity. Similarly, monospecific antibodies differentiate between allelic variants of merozoite surface proteins (13, 23), but the human antibody response is commonly directed at conserved or semiconserved epitopes (8, 34) and direct evidence for the evasion of antibody-dependent immunity is lacking.Comparison of the frequencies of nonsynonymous-to-synonymous mutations (20) for P. falciparum genes provides evidence of diversifying selection in msp-1 (11), which encodes merozoite surface protein-1, but the data are less clear for msp-2, which encodes merozoite surface protein-2 (9, 11, 21), and the significance of the findings is uncertain, given the limitations of the method (37). Comparison of intra-and interpopulation variances in allele frequencies provides evidence for selection on a polymorphic region of msp-1 (5) and dimorphic regions of msp-2 (4), but there are no data for polymorphic regions of msp-2. Comparison of inter-and intraspecific levels of variation suggests balancing selection on the erythrocyte-binding antigen EBA-175 (25) and the apical membrane antigen AMA-1 (22). However, except for msp-1, for which selection may be mediated by strain-specific antibo...

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Genetic Diversity and Antigenic Polymorphism in Plasmodium falciparum : Extensive Serological Cross-Reactivity between Allelic Variants of Merozoite Surface Protein 2

et al. 2003

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“…13 In addition, three sequence classes of the amplified block 2 of the MSP-1 gene, denoted K1, MAD20, and RO33, 14 and two of block 3 of the MSP-2, denoted IC1 and FC27, were identified by sequence-specific probes hybridized to Southern blots of the PCR-amplified fragments. 15 In addition, a probe was used that recognizes alleles of the FC27 form of MSP-2 that lacks the 12 amino acid repeat 16 denoted SUD (5Ј-GTTCA-AGTTCTGGCAATGCA-3Ј).…”

Section: Methodsmentioning

confidence: 99%

Characteristics of Plasmodium falciparum parasites that survive the lengthy dry season in eastern Sudan where malaria transmission is markedly seasonal.

et al. 1998

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Abstract. We have examined 83 inhabitants of Asar village in eastern Sudan, where malaria transmission lasts approximately 2-3 months each year, for the presence of Plasmodium falciparum during the prolonged dry season. All patients were treated with a standard dose of chloroquine following the first diagnosis, then examined by microscopy and the polymerase chain reaction (PCR) every two weeks for the first two months and subsequently once each month for the next 15 months throughout the dry season until the following transmission season. The PCR primers used amplified polymorphic regions of the merozoite surface protein-1 (MSP-1), MSP-2, and glutamate-rich protein genes. Results show that subpatent and asymptomatic parasitemias persisted in some patients for several months throughout the dry season, often as genetically complex infections. Different genotypes could coexist together in a single infection and the proportions of each could fluctuate dramatically during this period. However, in some individuals, single genotypes appeared to persist for several months. Reappearance of clinical symptoms among patients with chronic infections was often associated with appearance of new alleles, indicating reinfections with parasites of novel genotypes.In the poor savannah area of eastern Sudan, the malaria transmission season is short and confined to approximately three rainy months of the year. In this region, the epidemiology of malaria is consistent with that of a hypoendemic area, where transmission occurs only following rains. A brief expansion of the mosquito population at this time leads to malaria outbreaks in October and November each year. However, during the long dry season from January to June, apart from a few clinical reports, very little is known about parasite reservoirs, or whether mosquitoes continue to transmit the parasite. A previous entomologic study suggested that the main mosquito vector, Anopheles arabiensis, retracts to scanty breeding sites where it can survive the dry season with continuous feeding activity but an incomplete reproductive cycle. 1 Nothing is known about how the long dry season influences the dynamics and the structure of the parasite populations in this region.During the past seven years, we have carried out regular surveys of the Plasmodium falciparum population in October-November in Asar village in eastern Sudan. 2,3 The principal findings have been that 1) a considerable amount of allelic polymorphism exists among the genes of parasites infecting patients at this time of the year, 2) no two patients are infected with identical parasite clones, and 3) most patients are infected with a mixture of parasite clones. A great diversity was found even among parasites that caused the very early malaria cases in the transmission season. 3 Such a level of diversity suggests that the parasites that appear at this time of the year may belong to a large parasite reservoir existing prior to the beginning of the rainy season. A recent study in a neighboring village has shown that sub-pa...

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“…[10][11][12] Many studies have identified the presence of B-cell epitopes in the repeats of circumsporozoite protein (CSP), liver stage antigen-1 (LSA-1), and merozoite surface protein-2 (MSP-2) of P. falciparum. [13][14][15][16] These antigens are also vaccine candidate antigens against sporozoite, liver, and blood stage parasites, respectively. In vitro studies have revealed that antibodies directed against the CSP repeats can inhibit sporozoite invasion into cultured liver cells and administration of such antibodies can completely protect mice and monkeys against sporozoite-induced malaria.…”

Section: Introductionmentioning

confidence: 99%

Antibody responses to repetitive epitopes of the circumsporozoite protein, liver stage antigen-1, and merozoite surface protein-2 in infants residing in a Plasmodium falciparum-hyperendemic area of western Kenya. XIII. Asembo Bay Cohort Project.

Zhou¹,

Xiao²,

Branch³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. The present study was initiated to characterize antibody responses to repetitive epitopes of the circumsporozoite protein (CSP), liver stage antigen-1 (LSA-1), and merozoite surface protein-2 (MSP-2) of Plasmodium falciparum in infants residing in a P. falciparum-hyperendemic area of western Kenya. In this study, development and maintenance of these antibody responses in 28 infants were studied longitudinally by use of monthly serum samples collected from birth to age 1 year. Mother plasma and infant umbilical cord plasma were also tested to assess the transplacental transfer of maternal antibodies. Results showed that antibodies passively transferred from mothers were detectable for CSP, LSA-1, and MSP-2 repeat epitopes. Infants were able to mount and maintain a strong antibody response against LSA-1 in their first year of life. Infants often responded to CSP repeats, but with a much lower antibody titer. Antibody responses in infants against Fc27 and 3D7 repeats of MSP-2 were low throughout their first year. In addition, 51 infants whose first detected infection occurred at Ͼ 4 months of age were selected to determine antibody responses to the antigens tested upon their first and second detected infections. Antibody responses to LSA-1 and, to a lesser degree, CSP increased in positivity rates and titer upon second infection. Antibody responses to Fc27-type and 3D7-type repeats of MSP-2 were low upon both infections. There was no association between maternally transferred anti-LSA-1, anti-CSP, or anti-MSP-2 antibodies and an infant's first detected infection. No significant correlation was found between an infant's antibody responses to the 4 antigen repetitive epitopes and protection against malarial parasitemia during the first year of life.

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Differential antibody recognition of FC27‐like Plasmodium falciparum merozoite surface protein MSP2 antigens which lack 12 amino acid repeats

Cited by 33 publications

References 23 publications

Genetic Diversity and Antigenic Polymorphism in Plasmodium falciparum : Extensive Serological Cross-Reactivity between Allelic Variants of Merozoite Surface Protein 2

Genetic Diversity and Antigenic Polymorphism in Plasmodium falciparum : Extensive Serological Cross-Reactivity between Allelic Variants of Merozoite Surface Protein 2

Characteristics of Plasmodium falciparum parasites that survive the lengthy dry season in eastern Sudan where malaria transmission is markedly seasonal.

Antibody responses to repetitive epitopes of the circumsporozoite protein, liver stage antigen-1, and merozoite surface protein-2 in infants residing in a Plasmodium falciparum-hyperendemic area of western Kenya. XIII. Asembo Bay Cohort Project.

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