Patterns of Antigen Expression in Asexual Blood Stages and Gametocytes of Plasmodium falciparum

Bianco, Angelica; Pe, Crewther; Rl, Coppel; Hd, Stahl; Dj, Kemp; Rf, Anders; Gv, Brown

doi:10.4269/ajtmh.1988.38.258

Cited by 22 publications

(13 citation statements)

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“…Indirect IFAs showed that these antibodies reacted with AMA1 in P. falciparum-infected erythrocytes, and the IFA titer also increased with the number of immunizations, reaching 1:81,000 to 1:243,000 after the third immunization. The punctate immunofluorescence pattern seen for schizont-stage parasites in the IFAs was consistent with the IF pattern previously reported for AMA1 (4,26). In addition, the results from IFAs conducted on thin blood smears of asynchronous parasite cultures showed free merozoites with intense apical fluorescence and weaker surface fluorescence (Fig.…”

Section: Resultssupporting

confidence: 76%

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Specificity of the Protective Antibody Response to Apical Membrane Antigen 1

2001

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Apical membrane antigen 1 (AMA1) is considered one of the leading candidates for inclusion in a vaccine against blood stages of Plasmodium falciparum. Although the ama1 gene is relatively conserved compared to those for some other potential vaccine components, numerous point mutations have resulted in amino acid substitutions at many sites in the polypeptide. The polymorphisms in AMA1 have been attributed to the diversifying selection pressure of the protective immune responses. It was therefore of interest to investigate the impact of sequence diversity in P. falciparum AMA1 on the ability of anti-AMA1 antibodies to inhibit the invasion of erythrocytes in vitro by P. falciparum merozoites. For these studies, we used antibodies to recombinant P. falciparum 3D7 AMA1 ectodomain, which was prepared for testing in early clinical trials. Antibodies were raised in rabbits to the antigen formulated in Montanide ISA720, and human antibodies to AMA1 were isolated by affinity purification from the plasma of adults living in regions of Papua New Guinea where malaria is endemic. Both rabbit and human anti-AMA1 antibodies were found to be strongly inhibitory to the invasion of erythrocytes by merozoites from both the homologous and two heterologous lines of P. falciparum. The inhibitory antibodies targeted both conserved and strain-specific epitopes within the ectodomain of AMA1; however, it appears that the majority of these antibodies reacted with strain-specific epitopes in domain I, the N-terminal disulfide-bonded domain, which is the most polymorphic region of AMA1.

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Section: Resultssupporting

confidence: 76%

“…Synchronized 3D7 schizonts at 4% parasitemia and 4% hematocrit were pelleted from culture and washed three times with RPMI 1640-25 mM HEPES-24 mM NaHCO 3 buffer. Thin smears for analysis of parasite morphology were prepared as described elsewhere (4). Thick smears were prepared on 12-well multitest microscope slides (ICN, Aurora, Ohio).…”

Section: Methodsmentioning

confidence: 99%

Specificity of the Protective Antibody Response to Apical Membrane Antigen 1

2001

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“…Since the traditional role for HSP40 proteins is as chaperones, a possible role for PfGECO could be to assist with the correct folding and transport of other proteins exported during gametocytogenesis. Using IFA we examined whether the absence of PfGECO affected the correct localization of known exported proteins Pfg.748, MESA, and SBP1 in gametocytes (10,31). In the wild-type strain 3D7, Pfg.748 localized to the PV in stage I gametocytes as previously reported (Fig.…”

Section: Figmentioning

confidence: 83%

“…4A). MESA is known to be expressed in both asexual parasites and gametocytes and localizes to the RBC membrane (10). Colocalization studies with PfGECO and MESA antisera show that MESA localizes to the RBC surface of all gametocyte stages and that this staining pattern is external to PfGECO (Fig.…”

Section: Pfgeco Transcription Is Upregulated In Early Gametocytesmentioning

confidence: 99%

Functional Analysis of the Exported Type IV HSP40 Protein PfGECO in Plasmodium falciparum Gametocytes

et al. 2011

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During Plasmodium falciparum infection, host red blood cell (RBC) remodeling is required for the parasite's survival. Such modifications are mediated by the export of parasite proteins into the RBC that alter the architecture of the RBC membrane and enable cytoadherence. It is probable that some exported proteins also play a protective role against the host defense response. This may be of particular importance for the gametocyte stage of the life cycle that is responsible for malaria transmission, since the gametocyte remains in contact with blood as it proceeds through five morphological stages (I to V) during its 12-day maturation. Using microarray analysis, we identified several genes with encoded secretory or export sequences that were differentially expressed during early gametocytogenesis. One of these, PfGECO, encodes a predicted type IV heat shock protein 40 (HSP40) that we show is expressed in gametocyte stages I to IV and is exported to the RBC cytoplasm. HSPs are traditionally induced under stressful conditions to maintain homeostasis, but PfGECO expression was not increased upon heat shock, suggesting an alternate function. Targeted disruption of PfGECO indicated that the gene is not essential for gametocytogenesis in vitro, and quantitative reverse transcriptase PCR (RT-PCR) showed that there was no compensatory expression of the other type IV HSP40 genes. Although P. falciparum HSP40 members are implicated in the trafficking of proteins to the RBC surface, removal of PfGECO did not affect the targeting of other exported gametocyte proteins. This work has expanded the repertoire of known gametocyte-exported proteins to include a type IV HSP40, PfGECO.

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“…The coverslips were washed again after incubation, mounted in 70% glycerol in PBS, and examined at a magnification of x400 or x1,000 with a fluorescent microscope (Zeiss, Standar Model, Oberkoche, West Germany). When required, nuclear counter-staining of parasites was done with propidium iodide (PI, Sigma; Bianco et al 1988).…”

Section: Immunofluorescence Assaysmentioning

confidence: 99%

Plasmodium vivax and P. chabaudi: inter-species cross-reacting antigens

Pérez

Guzmán-Bracho

Romano

et al. 1997

Parasitology Research

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A monoclonal antibody raised by immunization of BALB/c mice with erythrocytic stages of Plasmodium vivax was shown to react with asexual erythrocytic stages of P. chabaudi. The cross-reactivity molecules are antigens of 200 and 148 kDa in P. vivax and of 190 and 70 kDa in P. chabaudi. Immunofluorescence studies of the erythrocytic stages of P. vivax and P. chabaudi indicated that expression of these antigens increased as the parasites' developed from the ring stage to the schizont stage. In the mature trophozoites of P. chabaudi, immunoelectron microscopy revealed clusters of antigen distributed in the cytoplasm of the parasitized erythrocyte. In the schizont, packets of antigen were found associated with the parasitophorous vacuole and the cytoplasm of the infected host cell.

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Patterns of Antigen Expression in Asexual Blood Stages and Gametocytes of Plasmodium falciparum

Cited by 22 publications

References 0 publications

Specificity of the Protective Antibody Response to Apical Membrane Antigen 1

Specificity of the Protective Antibody Response to Apical Membrane Antigen 1

Functional Analysis of the Exported Type IV HSP40 Protein PfGECO in Plasmodium falciparum Gametocytes

Plasmodium vivax and P. chabaudi: inter-species cross-reacting antigens

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