Identification of<i>Plasmodium</i>GAPDH epitopes for generation of antibodies that inhibit malaria infection

Jae, Sung Myung; McLean, Kyle Jarrod; Jacobs-­Lorena, Marcelo

doi:10.26508/lsa.201800111

Cited by 11 publications

(7 citation statements)

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“…Murine parasite species and Pf required the receptor CD68 (scavenger receptor D1) to enter Kupffer cells in vivo and in vitro [56]. A candidate to interact with CD68 is the Pb GAPDH (glyceraldehyde 3-phosphate dehydrogenase) [57].…”

Section: Box 2 Biogenesis and Exocytosis Of Micronemes And Rhoptries In Sporozoitesmentioning

confidence: 99%

Secretory Organelle Function in the Plasmodium Sporozoite

Arredondo

Schepis

Reynolds

et al. 2021

Trends in Parasitology

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Section: Box 2 Biogenesis and Exocytosis Of Micronemes And Rhoptries In Sporozoitesmentioning

confidence: 99%

Secretory Organelle Function in the Plasmodium Sporozoite

Arredondo

Schepis

Reynolds

et al. 2021

Trends in Parasitology

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“…Another example is Romiplostim (Nplate®), a thrombopoietin receptor agonist used to treat thrombocytopenia ( Cwirla et al, 1997 ; Keating, 2012 ; Tarantino et al, 2019 ). The phage display approach led to the identification of a peptide that structurally mimics glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Plasmodium sporozoites; this peptide became a new vaccine candidate for targeting malaria liver invasion ( Cha et al, 2016 , 2018 ). The phage display approach was used to search for mimotopes of the Trypanosoma brucei variant surface glycoprotein (VSG).…”

Section: Discussionmentioning

confidence: 99%

“…Entry of the host cell is essential to complete the parasite’s life cycle and infection spread, thus this is a promising target for the development of new therapeutic strategies ( Walker et al, 2013 ). In this work, we used the same phage library that was used to identify a GAPDH ligand molecule on the surface of the invasive Plasmodium sporozoite ( Cha et al, 2016 , 2018 ). Here we showed that the N3 peptide binds to the T. cruzi invasive forms ( Lima et al, 2010 ; Salassa and Romano, 2018 ) and importantly, by doing so, inhibits target cell infection.…”

Section: Discussionmentioning

confidence: 99%

The Screen of a Phage Display Library Identifies a Peptide That Binds to the Surface of Trypanosoma cruzi Trypomastigotes and Impairs Their Infection of Mammalian Cells

Paula¹,

Lopes-Torres

Jacobs-Lorena

et al. 2022

Front. Microbiol.

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BackgroundChagas is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. On the order of seven million people are infected worldwide and current therapies are limited, highlighting the urgent need for new interventions. T. cruzi trypomastigotes can infect a variety of mammalian cells, recognition and adhesion to the host cell being critical for parasite entry. This study focuses on trypomastigote surface ligands involved in cell invasion.MethodsThree selection rounds of a phage peptide display library for isolation of phages that bind to trypomastigotes, resulted in the identification of the N3 dodecapeptide. N3 peptide binding to T. cruzi developmental forms (trypomastigotes, amastigotes and epimastigotes) was evaluated by flow cytometry and immunofluorescence assays. Parasite invasion of Vero cells was assessed by flow cytometry and immunofluorescence assays.ResultsPhage display screening identified the N3 peptide that binds preferentially to the surface of the trypomastigote and amastigote infective forms as opposed to non-infective epimastigotes. Importantly, the N3 peptide, but not a control scrambled peptide, inhibits trypomastigote invasion of Vero cells by 50%.ConclusionThe N3 peptide specifically binds to T. cruzi, and by doing so, inhibits Vero cell infection. Follow-up studies will identify the molecule on the parasite surface to which the N3 peptide binds. This putative T. cruzi ligand may advance chemotherapy design and vaccine development.

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“…Mice were immunized twice at 2-week intervals. Serum was collected 14–21 days after administration of the last booster ( Cha et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Combining transgenesis with paratransgenesis to fight malaria

Huang

Vega-Rodríguez

Kizito

et al. 2022

eLife

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Malaria is among the deadliest infectious diseases, and Plasmodium, the causative agent, needs to complete a complex development cycle in its vector mosquito for transmission to occur. Two promising strategies to curb transmission are transgenesis, consisting of genetically engineering mosquitoes to express antimalarial effector molecules, and paratransgenesis, consisting of introducing into the mosquito commensal bacteria engineered to express antimalarial effector molecules. Although both approaches restrict parasite development in the mosquito, it is not known how their effectiveness compares. Here we provide an in-depth assessment of transgenesis and paratransgenesis and evaluate the combination of the two approaches. Using the Q-system to drive gene expression, we engineered mosquitoes to produce and secrete two effectors – scorpine and the MP2 peptide – into the mosquito gut and salivary glands. We also engineered Serratia, a commensal bacterium capable of spreading through mosquito populations to secrete effectors into the mosquito gut. Whereas both mosquito-based and bacteria-based approaches strongly reduced the oocyst and sporozoite intensity, a substantially stronger reduction of Plasmodium falciparum development was achieved when transgenesis and paratransgenesis were combined. Most importantly, transmission of Plasmodium berghei from infected to naïve mice was maximally inhibited by the combination of the two approaches. Combining these two strategies promises to become a powerful approach to combat malaria.

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Identification ofPlasmodiumGAPDH epitopes for generation of antibodies that inhibit malaria infection

Abstract: This study reports on the identification of two Plasmodium GAPDH epitope peptides that are responsible for sporozoite–Kupffer cell interaction and act as antigens against malaria infection.

Cited by 11 publications

References 35 publications

Secretory Organelle Function in the Plasmodium Sporozoite

Secretory Organelle Function in the Plasmodium Sporozoite

The Screen of a Phage Display Library Identifies a Peptide That Binds to the Surface of Trypanosoma cruzi Trypomastigotes and Impairs Their Infection of Mammalian Cells

Combining transgenesis with paratransgenesis to fight malaria

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