Natural human immunoglobulin G subclass responses to Plasmodium falciparum serine repeat antigen in Uganda.

Okech, Brenda; Nalunkuma, A; Okello, Denis; Pang, Xin-Li; Suzue, Kazutomo; Li, Jie; Horii, Toshihiro; Egwang, Thomas G.

doi:10.4269/ajtmh.2001.65.912

Cited by 42 publications

(36 citation statements)

References 23 publications

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“…Recombinant SERA4 was recognized by all three pools of human sera, whereas SERA2, SERA3, and SERA5 fusion proteins were recognized by one or two of the PNG pooled sera. The finding that not all PNG sera recognize the SERA5 recombinant antigen is consistent with a previous study using sera from Ugandan adults living in a holoendemic area (41). In contrast, other recombinant SERA proteins were not recognized by any of the PNG antibodies.…”

Section: Figsupporting

confidence: 81%

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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Section: Figsupporting

confidence: 81%

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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“…Our previous work (17) showed an epidemiological correlation between the antibody titer against the SERA5 N-terminal region and apparent malaria fever and blood parasitemia. Here we have shown that antibody titer against SERA5 positively correlated with the serum inhibition of parasite growth (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…8F), suggesting that the immune response against each antigen is independent. It has been reported that the IgG antibody level to SE47Ј is negatively correlated with a blood parasitemia in a group of children in a malaria holoendemic area (17), suggesting that the serum of a group of children, in which the IgG titer against SE47Ј is high, retains the antiparasitic activity. We examined whether the serum from 40 Ugandan adults inhibits in vitro parasite growth.…”

Section: Immunogenicity Of Sera3 Sera4 Sera5 and Sera6mentioning

confidence: 99%

“…Recombinant proteins corresponding to the 47-kDa domain of SERA conferred protective immunity in Aotus and squirrel monkeys against the parasite challenges ( [13][14][15][16]. The epidemiological study in a holoendemic area of Uganda has revealed that increased level of IgG against 47-kDa peptide correlates with lower parasitemias in the peripheral blood and absence of fever in a group of children, but IgG level against 50-kDa peptide does not (17). Thus, the N-terminal domain of SERA is a promising candidate for a malaria vaccine.…”

mentioning

confidence: 99%

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Serine Repeat Antigen (SERA5) Is Predominantly Expressed among the SERA Multigene Family of Plasmodium falciparum, and the Acquired Antibody Titers Correlate with Serum Inhibition of the Parasite Growth

Aoki

Itagaki

et al. 2002

Journal of Biological Chemistry

100

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The Plasmodium falciparum serine repeat antigen (SERA) is one of the blood stage malaria vaccine candidates. The malaria genome project has revealed that SERA is a member of the SERA multigene family consisting of eight SERA homologues clustered on chromosome 2 and one SERA homologue on chromosome 9. Northern blotting and real time quantitative reverse transcription-PCR with five independent parasite strains, including three allelic representative forms of the SERA gene, have shown that all of the SERA homologues are transcribed most actively at trophozoite and schizont stages and that SERA5 (SERA/SERP) is transcribed predominantly among the family. Polyclonal antibodies were raised against recombinant proteins representing the Nterminal portions of four significantly transcribed SERA homologues (SERA3 to -6) in the center of the cluster on chromosome 2. Using these antibodies, indirect immunofluorescence microscopy detected the expression of SE-RA3 to -6, with similar localization, in all trophozoite-and schizont-infected erythrocytes. We have examined 40 sera from Ugandan adults for their antibody reactivity and found that enzyme-linked immunosorbent assay titer against SERA5 N-terminal domain, but not against other SERA proteins, is positively correlated with the inhibition of in vitro parasite growth by individual sera. Our data confirm the usefulness of the N-terminal domain of SERA5 as a promising malaria candidate vaccine.

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“…P. falciparum SERA5 is a vaccine candidate molecule now on clinical trial in Uganda (Horii et al, 2010). Serum antibodies against the N-terminal domain of P. falciparum SERA5 in individuals living in malaria endemic area protect infants from clinical malaria and inhibit in vitro parasite growth (Okech et al, 2001(Okech et al, , 2006Aoki et al, 2002;Horii et al, 2010). During blood stage growth, all SERA gene family member of P. falciparum are transcribed most actively at trophozoite and schizont stages.…”

Section: Conclusion and Open Issues In Sera Studymentioning

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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Natural human immunoglobulin G subclass responses to Plasmodium falciparum serine repeat antigen in Uganda.

Cited by 42 publications

References 23 publications

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

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

Serine Repeat Antigen (SERA5) Is Predominantly Expressed among the SERA Multigene Family of Plasmodium falciparum, and the Acquired Antibody Titers Correlate with Serum Inhibition of the Parasite Growth

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

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