Aldolase Activity of a
            <i>Plasmodium falciparum</i>
            Protein with Protective Properties

Certa, Ulrich; Ghersa, Paola; Döbeli, Heinz; Matile, Hugues; Kocher, Hans P.; Shrivastava, Indresh K.; Shaw, Alan; Perrin, Luc

doi:10.1126/science.3285469

Cited by 81 publications

(24 citation statements)

References 20 publications

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“…Accumulating evidence suggests that intracellular antigens can serve as protecting epitopes against parasitic diseases (Dessein et al 1988;Wain et al 1994;Sher et al 1989;Certa et al 1988). Lubega et al (2002) demonstrated that mice vaccinated with native tubulin from T. brucei could be protected against T. brucei, T. congolense, and T. rhodesiense challenges.…”

Section: Discussionmentioning

confidence: 99%

Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection

Yang

et al. 2008

Parasitol Res

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Actin gene of Trypanosoma evansi (STIB 806) was cloned and expressed in Escherichia coli. The predicted amino acid sequence of T. evansi actin shows 100%, 98.7%, and 93.1%, homology with Trypanosoma equiperdum, Trypanosoma brucei brucei, and Trypanosoma cruzi. Recombinant actin was expressed as inclusion bodies in E. coli. It was purified and renatured for immunological studies. Mice immunized with the renatured recombinant actin were protected from lethal challenge with T. evansi STIB 806, T. equiperdum STIB 818, and T. b. brucei STIB 940, showing 63.3%, 56.7%, and 53.3% protection, respectively. Serum collected from the rabbit immunized with recombinant actin inhibited the growth of T. evansi, T. equiperdum, and T. b. brucei in vitro cultivation. Serum from mice and rabbits immunized with recombinant actin only recognized T. evansi actin but not mouse actin. The results of this study suggest that the recombinant T. evansi actin induces protective immunity against T. evansi, T. equiperdum, and T. b. brucei infection and may be useful in the development of a vaccine with other cytoskeletal proteins to prevent animal trypanosomiasis caused by these three trypanosome species.

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Section: Discussionmentioning

confidence: 99%

Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection

Yang

et al. 2008

Parasitol Res

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“…Cloning and a high level of expression of genes encoding P. falciparum enzyme activities would permit studies on the structure and function of the parasiteÕs metabolic enzymes, eventually leading to identification of drugs that can selectively inhibit certain parasitic enzymes. The focus has been on cloning glycolytic pathway genes in P. falciparum because it is known that it relies on anaerobic glycolysis for energy production during the erythrocytic stages (Certa et al 1988; Kaslow and Hill 1990;Hicks et al 1991). However, its genome sequence revealed that many other biochemical pathways could also be reconstructed , suggesting the existence of yet uncharacterized pathways that may be essential for the parasiteÕs pathogenicity.…”

Section: Introductionmentioning

confidence: 98%

Functional characterization of an alternative [lactate dehydrogenase-like] malate dehydrogenase in Plasmodium falciparum

Chan

Sim

2004

Parasitology Research

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The catalysis of malate dehydrogenase (MDH) in Plasmodium falciparum (pfMDH) which involves NAD/NADH coupling is crucial for the parasite's pathogenicity. Primers were designed based on the P. falciparum genome resource, and these facilitated the cloning of a gene coding for pfMDH from a local clinical isolate. The DNA sequence of the cloned gene revealed an open-reading frame that encodes a protein of 313 amino acids. After induction in Escherichia coli BL21, enzyme assays of the expressed pfMDH purified by affinity chromatography exhibited significant enzyme activity of about 50 U/mg, where one unit (U) of enzyme activity is defined as the amount of enzyme oxidising 1 microol NADH/min. Based on its phylogenetic status amongst MDHs and lactate dehydrogenases (LDHs), the cloned gene was clearly defined as belonging to the NADH-dependent [LDH-like] MDHs. It is noteworthy that pfMDH harbours unique structural characteristics potentially useful for screening drugs specific for disabling parasitic enzymes.

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“…The other recombinant protein included in this study is a protein ofMr 41,000 (termed p41), which was identified as the aldolase of the parasite (4,11). The parasite-derived antigen preparation gave a marked degree of protection against malaria in immunized Saimiri monkeys (4).…”

mentioning

confidence: 99%

“…The parasite-derived antigen preparation gave a marked degree of protection against malaria in immunized Saimiri monkeys (4). Probably for functional reasons, the entire polypeptide sequence is highly conserved in all P. falciparum isolates analyzed (11). The central function of aldolase for parasite metabolism makes it unlikely that mutants due to immunoselection will appear after immunization.…”

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confidence: 99%

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Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins.

Herrera

Perlaza

et al. 1990

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

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The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falkiparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe the vaccination of Aotus monkeys with two recombinant blood-stage antigens (recombinant p41 and 190N) that were considered as vaccine candidates because parasite-derived antigen preparations could protect susceptible monkeys from an otherwise lethal malaria infection. In contrast to the natural antigen, recombinant p41 protein (P. falciparum aldolase) could not protect monkeys, although all animals seroconverted. 190N antigen, a recombinant protein containing conserved sequences of the major merozoite surface antigen p190, protected two of five monkeys from critical levels ofinfection with the highly virulent FVO isolate of P. falckarum. However, the B-and T-cell responses to 190N antigen were similar in protected and unprotected animals so that other unknown factors may contribute to protection. Higher purity or lack of protective epitopes or different structure of protective epitopes in the recombinant proteins might explain the better performance of parasite-derived antigens in vaccination trials. The partial protection obtained with 190N antigen suggests that this molecule could contribute to a vaccine mixture against P. falciparum.

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Aldolase Activity of a Plasmodium falciparum Protein with Protective Properties

Cited by 81 publications

References 20 publications

Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection

Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection

Functional characterization of an alternative [lactate dehydrogenase-like] malate dehydrogenase in Plasmodium falciparum

Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins.

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