Protein p126: a parasitophorous vacuole antigen associated with the release of <i>Plasmodium falciparum</i> merozoites

Delplace, Patrick; Bhatia, Aruna; Cagnard, Maryvonne; Camus, Daniel; Colombet, G; Debrabant, Alain; Dubremetz, Jean-Franc ̧ois; Dubreuil, Nicole; Prensier, G.; Fortier, B; Haq, A. al; Weber, James L.; Vernes, A

doi:10.1016/0248-4900(88)90080-9

Cited by 72 publications

(60 citation statements)

References 9 publications

(10 reference statements)

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“…The first, based on the polymorphism of this domain of the molecule, results in a decrease in immune specificity. A deletion of one repeat of the N-terminal domain has already been described, which indicates that p126 can be expressed with five 7, 31 instead of six 8,26 repeats of eight amino acids. Moreover, it has been observed that 88% of the P. falciparum isolates collected in the same area where we conducted our study contained six repeats and the remaining 12% contained five repeats (Zalis MZ, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans.

Banic¹,

Oliveira-Ferreira²,

Pratt-Riccio³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. A parasitophorous vacuole protein of Plasmodium falciparum, p126, is a potential candidate for a malaria vaccine. Its N-terminal region, composed of six repeats of eight amino acids, appears to be involved in the induction of protective immunity against P. falciparum challenge in monkeys. This study evaluated the immune response to p126 and to its N-terminal region (Nt47) in patients (n ϭ 45) living in a malaria-endemic area of Brazil (Colina, Porto Velho, Rondonia). Cellular proliferative responses against Nt47 were low and infrequent. The study of the humoral immune response demonstrated that 95% of the patients had detectable anti-p126 antibodies and 77% had anti-Nt47 antibodies. Analysis of the antibody isotypes specific for Nt47 revealed that all four IgG subclasses were present and individuals with higher levels of anti-Nt47 cytophilic IgG antibody (IgG1 ϩ IgG3/IgG2 ϩ IgG4) had significantly lower parasitemia levels, suggesting that antibodies to the N-terminal region of the p126 protein may contribute to acquisition of immunity to P. falciparum malaria.The Plasmodium falciparum p126 antigen 1 is synthesized by the parasite between the 32nd and the 36th hr of a 42-hr erythrocytic cycle, then stored inside the parasitophorous vacuole. This antigen is processed into fragments of 50 and 73 kD, the latter one composed of two peptides of 47 and 18 kD linked by disulfide bridges. This processing is associated with the release of merozoites from mature schizonts. 2 The p126 protein, also known as serine-rich antigen 3 or serine-rich protein 4 based on the similarity of coding genes, ranks as a candidate antigen for inclusion in a subunit vaccine to control the asexual erythrocytic phase of P. falciparum malaria for the following reasons: 1) it is antigenically conserved among different strains of P. falciparum; 5 2) monoclonal and polyclonal antibodies specific for p126 inhibit the in vitro growth of the parasite; 6-9 and 3) it can induce partial protection against parasite challenge in various species of monkeys. 1,3,[10][11][12] Moreover, the N-terminal portion (located at the amino-terminal end of the 47-kD subfragment) is involved in the induction of this protective immunity. 13,14 In view of these encouraging results, we focused on the six repeats of eight amino acids at the N-terminal end of the molecule 15 (Nt47) since this domain 1) includes a B and T cell epitope recognized by infected humans 16 (Roussilhon C, unpublished data); and 2) is the only one of the C-and Nterminal regions of the processed fragments of p126 that is able to induce an antibody response in mice immunized with respective peptides. 17 However, mice did not develop antibodies against this domain of the molecule when immunized with schizont-infected erythrocytes. 16 It is therefore of great value for vaccine design to determine the degree of immunogenicity of the Nt47 domain in humans living in a malaria-endemic area and naturally exposed to plasmodial antigens. In this respect, we investigated the immune response to Nt47 an...

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Section: Discussionmentioning

confidence: 99%

“…A synthetic peptide corresponding to the repeat region of the amino terminus of p126 15,26 was prepared using a solid-phase method 27 as previously described. 17 This peptide was called Nt47 because of its localization at the amino terminus of the 47-kD subfragment of p126.…”

Section: Patientsmentioning

confidence: 99%

Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans.

Banic¹,

Oliveira-Ferreira²,

Pratt-Riccio³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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“…Phylogenetic analysis performed on all known Plasmodium SERA genes reveals that SERA9 is most closely related to the other P. falciparum SERA genes with an "active site" serine. 5 The origins and function of this "rouge" SERA gene remain to be determined; however, at present, there are no obvious features that distinguish this gene from SERA1-SERA5.…”

Section: Centrally Located Sera Genes Are Transcribed More Strongly Tmentioning

confidence: 99%

“…This is in contrast to the expression pattern for the KAHRP control that is transcribed earlier in the parasite life cycle as expected. Note that since the SERA9 gene was not available 5 M. Delorenzi and B. S. Crabb, unpublished data. until relatively recently, it was not included in this experiment.…”

Section: Centrally Located Sera Genes Are Transcribed More Strongly Tmentioning

confidence: 99%

A Subset of Plasmodium falciparum SERA Genes Are Expressed and Appear to Play an Important Role in the Erythrocytic Cycle

Miller¹,

Good

Drew³

et al. 2002

Journal of Biological Chemistry

160

173

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The Plasmodium falciparum serine repeat antigen (SERA) has shown considerable promise as a blood stage vaccine for the control of malaria. A related protein, SERPH, has also been described in P. falciparum. Whereas their biological role remains unknown, both proteins possess papain-like protease domains that may provide attractive targets for therapeutic intervention. Genomic sequencing has recently shown that SERA and SERPH are the fifth and sixth genes, respectively, in a cluster of eight SERA homologues present on chromosome 2. In this paper, the expression and functional relevance of these eight genes and of a ninth SERA homologue found on chromosome 9 were examined in blood stage parasites. Using reverse transcriptase-PCR and microarray approaches, we demonstrate that whereas mRNA to all nine SERA genes is synthesized late in the erythrocytic cycle, it is those genes in the central region of the chromosome 2 cluster that are substantially up-regulated at this time. Using antibodies specific to each SERA, it was apparent that SERA4 to -6, and possibly also SERA9, are synthesized in blood stage parasites. The reactivity of antibodies from malaria-immune individuals with the SERA recombinant proteins suggested that SERA2 and SERA3 are also expressed at least in some parasite populations. To examine whether SERA genes are essential to blood stage growth, each of the eight chromosome 2 SERA genes was targeted for disruption. Whereas genes at the periphery of the cluster were mostly dispensable (SERA2 and -3 and SERA7 and -8), those in the central region (SERA4 to -6) could not be disrupted. The inability to disrupt SERA4, -5, and -6 is consistent with their apparent dominant expression and implies an important role for these genes in maintenance of the erythrocytic cycle.

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“…As shown in Fig. 1., during the course of schizont rupture/merozoite release, SERA is proteolytically processed into a 47 kDa Nterminal (P47), a 50 kDa central (P50), an 18 kDa C-terminal (P18) and a 6 kDa domain (Delplace et al, 1987(Delplace et al, , 1988Debrabant et al, 1992;Li et al, 2002a). The N-terminal P47 fragment is further processed into two 25 kDa fragments (P25n and P25c) in some allelic types (Li et al, 2002a).…”

Section: Processing Of P Falciparum Sera5mentioning

confidence: 99%

Clues to Evolution of the SERA Multigene Family in the Genus Plasmodium

Arisue¹,

Palacpac²,

Tanabe³

et al. 2011

Gene Duplication

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Protein p126: a parasitophorous vacuole antigen associated with the release of Plasmodium falciparum merozoites

Cited by 72 publications

References 9 publications

Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans.

Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans.

A Subset of Plasmodium falciparum SERA Genes Are Expressed and Appear to Play an Important Role in the Erythrocytic Cycle

Clues to Evolution of the SERA Multigene Family in the Genus Plasmodium

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