Cloning and expression of the gene coding for the transmission blocking target antigen Pfs48/45 of Plasmodium falciparum

Kocken, Clemens H. M.; Jansen, Josephine; Kaan, Anita; Beckers, Pascal; Ponnudurai, T.; Kaslow, David C.; Konings, Ruud N. H.; Schoenmakers, John G.G.

doi:10.1016/0166-6851(93)90158-t

Cited by 119 publications

(74 citation statements)

References 29 publications

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“…P48/45 protein is a surface protein of both male and female malaria parasite gametes (39). Antibodies directed against P48/45 prevent zygote development, and P48/45 is under consideration as a target for a transmission-blocking vaccine to combat malaria (51). Disruption of the P48/45 gene results in a dramatic diminution of male-gamete fertility; the microgametes are unable to adhere to or penetrate macrogametes, and the number of oocysts produced is drastically reduced (39).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase

Sturm

Mollard

Cozijnsen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

115

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Mitochondrial ATP synthase is driven by chemiosmotic oxidation of pyruvate derived from glycolysis. Blood-stage malaria parasites eschew chemiosmosis, instead relying almost solely on glycolysis for their ATP generation, which begs the question of whether mitochondrial ATP synthase is necessary during the blood stage of the parasite life cycle. We knocked out the mitochondrial ATP synthase β subunit gene in the rodent malaria parasite, Plasmodium berghei, ablating the protein that converts ADP to ATP. Disruption of the β subunit gene of the ATP synthase only marginally reduced asexual blood-stage parasite growth but completely blocked mouse-to-mouse transmission via Anopheles stephensi mosquitoes. Parasites lacking the β subunit gene of the ATP synthase generated viable gametes that fuse and form ookinetes but cannot progress beyond this stage. Ookinetes lacking the β subunit gene of the ATP synthase had normal motility but were not viable in the mosquito midgut and never made oocysts or sporozoites, thereby abrogating transmission to naive mice via mosquito bite. We crossed the self-infertile ATP synthase β subunit knockout parasites with a male-deficient, self-infertile strain of P. berghei, which restored fertility and production of oocysts and sporozoites, which demonstrates that mitochondrial ATP synthase is essential for ongoing viability through the female, mitochondrion-carrying line of sexual reproduction in P. berghei malaria. Perturbation of ATP synthase completely blocks transmission to the mosquito vector and could potentially be targeted for disease control. malaria | ATP synthase | ookinetes | mitochondrial endosymbiosis | aerobic respiration

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Section: Discussionmentioning

confidence: 99%

Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase

Sturm

Mollard

Cozijnsen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

115

View full text Add to dashboard Cite

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“…The average size of the insert applied to the array was 1±2 kb, but some clones had PCR products as large as 5 kb. In addition to clones from this library, several previously characterized genes encoding stage-speci®c malarial surface antigens (MSP-1, Pfs25, Pfs28, Pfs48/45) were included in the prototype array (Holder, 1988;Kaslow et al, 1988;Duffy et al, 1993;Kocken et al, 1993).…”

Section: Array Constructionmentioning

confidence: 99%

Shotgun DNA microarrays and stage‐specific gene expression in Plasmodium falciparum malaria

Hayward

DeRisi

AlFadhli

et al. 2000

Molecular Microbiology

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203

100

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SummaryMalaria infects over 200 million individuals and kills 2 million young children every year. Understanding the biology of malarial parasites will be facilitated by DNA microarray technology, which can track global changes in gene expression under different physiological conditions. However, genomes of Plasmodium sp. (and many other important pathogenic organisms) remain to be fully sequenced so, currently, it is not possible to construct gene-speci®c microarrays representing complete malarial genomes. In this study, 3648 random inserts from a Plasmodium falciparum mung bean nuclease genomic library were used to construct a shotgun DNA microarray. Through differential hybridization and sequencing of relevant clones, large differences in gene expression were identi®ed between the blood stage trophozoite form of the malarial parasite and the sexual stage gametocyte form. The present study lengthens our list of stage-speci®c transcripts in malaria by at least an order of magnitude above all previous studies combined. The results offer an unprecedented number of leads for developing transmission blocking agents and for developing vaccines directed at blood stage antigens. A signi®cant fraction of the stage-selective transcripts had no sequence homologues in the current genome data bases, thereby underscoring the importance of the shotgun approach. The malarial shotgun microarray will be useful for unravelling additional important aspects of malaria biology and the general approach may be applied to any organism, regardless of how much of its genome is sequenced.

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“…3 Several P. falciparum antigens expressed either in gametocytes (Pfs48 and Pfs230) or in the mosquito parasite forms (Pfs25/28) have been identified and tested for their immunogenicity in animal models. [3][4][5][6] Recombinant Pfs25/28 and Pf230 proteins formulated in different adjuvants have been shown to induce high specific antibody titers in mice and primates that blocked P. falciparum transmission in mosquito artificial membrane feeding assay (MFA). [6][7][8][9][10] Recombinant Pfs48/45 protein was highly immunogenic in mice and rabbits, but expression of this protein in the correct conformation has proven difficult because the elicited antibodies failed to block parasite transmission to mosquitoes.…”

Section: Introductionmentioning

confidence: 99%

Induction of Transmission-Blocking Immunity in Aotus Monkeys by Vaccination With a Plasmodium Vivax Clinical Grade Pvs25 Recombinant Protein

Arévalo‐Herrera

Solarte

Yasnot

et al. 2005

The American Journal of Tropical Medicine and Hygiene

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Abstract. Aotus monkeys were used to determine the immunogenicity of Pvs25 protein expressed in the zygote/ ookinete surface. Animals were immunized in three times with 100 g of Pvs25 formulated in Montanide ISA-720. Antibodies to Pvs25 detected by an enzyme-linked immunosorbent assay appeared by day 30 after the first immunization, with a peak of antibodies levels on day 150. These antibodies were still detectable on day 300. Plasma samples on day 150 from experimental group were able to completely block the development of the parasite in Anopheles albimanus mosquitoes artificially fed with human isolates of Plasmodium vivax. Immunized Aotus monkeys were infected with blood forms of the P. vivax Salvador I strain and no boosting effect of blood infection on titers of antibodies to Pvs25 was observed despite the presence of infective gametocytes. In conclusion, Pvs25 protein formulated in Montanide ISA-720 induces efficient and long-lasting transmission-blocking antibodies that cannot be boosted by parasite infection.

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Cloning and expression of the gene coding for the transmission blocking target antigen Pfs48/45 of Plasmodium falciparum

Cited by 119 publications

References 29 publications

Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase

Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase

Shotgun DNA microarrays and stage‐specific gene expression in Plasmodium falciparum malaria

Induction of Transmission-Blocking Immunity in Aotus Monkeys by Vaccination With a Plasmodium Vivax Clinical Grade Pvs25 Recombinant Protein

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