Anti-CTLA-4 monoclonal antibody improves efficacy of the glyceraldehyde-3-phosphate dehydrogenase protein vaccine against Schistosoma japonicum in mice

Tang, Chaoliang; Yang, Jinfeng; Pan, Qun; Zhang, Ronghui; Xie, Ying; Xiong, Ying; Zhou, Hong-hua

doi:10.1007/s00436-019-06363-1

Cited by 7 publications

(8 citation statements)

References 27 publications

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“…Our results confirm an association of SmGAPDH with the tegumental surface of the worm. This further reconciles results that previously characterized SmGAPDH as a protective vaccine target (Argiro et al, 2000b;El Ridi and Tallima, 2013;Tallima et al, 2017;Tang et al, 2019). Before these results, how such an intracellular cytosolic enzyme might be accessed by damaging immune effectors was a conundrum.…”

Section: Discussionsupporting

confidence: 85%

“…GAPDH is best known as a key enzyme in glycolysis, facilitating the conversion of glyceraldehyde-3-phosphate (GAP) in the presence of nicotinamide adenide dinucleotide (NAD) to 1,3-bisphosphoglycerate (1,3BPG) and generating NADH (Seidler, 2013). S. mansoni GAPDH (SmGAPDH) has been previously expressed in an enzymatically active recombinant form (Argiro et al, 2000a;El Ridi et al, 2001, 2004, has been characterized as a potential vaccine candidate and has been shown to be a target for antibodies in the sera of schistosomiasisresistant individuals (Argiro et al, 2000a,b;Dessein et al, 1988;Goudot-Crozel et al, 1989;Tallima et al, 2017;Tang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Schistosoma mansoniglyceraldehyde-3-phosphate dehydrogenase enhances formation of the blood-clot lysis protein plasmin

2020

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Schistosomes are intravascular blood flukes that cause the parasitic disease schistosomiasis. In agreement with Schistosoma mansoni (Sm) proteomic analysis, we show here that the normally intracellular glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is also found at the parasite surface; live worms from all intravascular life stages display GAPDH activity. Suppressing GAPDH gene expression using RNA interference significantly lowers this live worm surface activity. Medium in which the worms are cultured overnight displays essentially no activity, showing that the enzyme is not shed or excreted but remains associated with the worm surface. Immunolocalization experiments confirm that the enzyme is highly expressed in the parasite tegument (skin). Surface activity in schistosomula amounts to ∼8% of that displayed by equivalent parasite lysates. To address the functional role of SmGAPDH, we purified the protein following its expression in Escherichia coli strain DS113. The recombinant protein displays optimal enzymatic activity at pH 9.2, shows robust activity at the temperature of the parasite's hosts, and has a Michaelis-Menten constant for glyceraldehyde-3-phosphate (GAP) of 1.4 mM±0.24. We show that recombinant SmGAPDH binds plasminogen (PLMG) and promotes PLMG conversion to its active form (plasmin) in a dose response in the presence of tissue plasminogen activator. Since plasmin is a key mediator of thrombolysis, our results support the hypothesis that SmGAPDH, a host-interactive tegumental protein that can enhance PLMG activation, could help degrade blood clots around the worms in the vascular microenvironment and thus promote parasite survival in vivo. This article has an associated First Person interview with the first author of the paper.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Schistosoma mansoniglyceraldehyde-3-phosphate dehydrogenase enhances formation of the blood-clot lysis protein plasmin

2020

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“…Th2 cells also stimulate B cells to produce immunoglobulins, such as IgE, which have been associated with resistance to reinfection after praziquantel treatment [34,61]. Regulatory T cells (Tregs) and B cells (Bregs) stimulate the production of IL-10 and TGF-β and other anti-inflammatory cytokines that downregulate granulomatous reactions in chronic infections, and inhibiting them has the potential to enhance vaccine efficacy [34,50,53,55,56,[62][63][64][65][66]. Furthermore, Th17 cells with IL-17, Th9, and follicular T helper cells are also important for hepatic granuloma formation and the regulation of the immune response to S. japonicum infections [56][57][58][59].…”

Section: Life Cycle and Immunopathologymentioning

confidence: 99%

“…It has been utilized alongside SjGST, SjTPI, and Sj23 DNA vaccines [70,110,111]. Furthermore, a series of studies have demonstrated that antibodies targeting T regulatory lymphocytes such as Monoclonal Antibodies to CD25 (anti-CD-25mAb) and Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), when administered as booster doses in immunization protocols, lead to significant improvements in vaccine efficacy [62][63][64][65]112]. Further studies are required to determine the feasibility and safety of this approach.…”

Section: The Role Of Adjuvants In the Development Of Schistosomiasis ...mentioning

confidence: 99%

“…S. japonicum Glyceraldehyde dehydrogenase (SjGAPDH) is a glycolytic enzyme important for the energy provision needed for the growth of the schistosomula [190]. It is expressed during all life cycle stages of the parasite, especially the schistosomula, and plays a critical role in the modification of intracellular signalling, activation and binding to plasminogen, inhibition of coagulation, and facilitation of the schistosome invasion and migration in the host [64,[190][191][192]. A combination of SjGAPDH with adjuvants like anti-CD25mAb and anti-CTLA-4 monoclonal antibodies resulted in sufficient protective efficacy against challenge infection [64,112,193].…”

Section: S Japonicum Calpains (Sj-p80)mentioning

confidence: 99%

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Transmission-Blocking Vaccines against Schistosomiasis Japonica

Zumuk,

Jones,

Navarro

et al. 2024

IJMS

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Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. Schistosoma japonicum is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000–2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.

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Mechanism by which the combination of SjCL3 and SjGAPDH protects against Schistosoma japonicum infection

Wei

Cheng

et al. 2020

Parasitol Res

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Anti-CTLA-4 monoclonal antibody improves efficacy of the glyceraldehyde-3-phosphate dehydrogenase protein vaccine against Schistosoma japonicum in mice

Cited by 7 publications

References 27 publications

Schistosoma mansoniglyceraldehyde-3-phosphate dehydrogenase enhances formation of the blood-clot lysis protein plasmin

Schistosoma mansoniglyceraldehyde-3-phosphate dehydrogenase enhances formation of the blood-clot lysis protein plasmin

Transmission-Blocking Vaccines against Schistosomiasis Japonica

Mechanism by which the combination of SjCL3 and SjGAPDH protects against Schistosoma japonicum infection

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