Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases

Ridi, Rashika El; Tallima, Hatem; Dalton, John P.; Donnelly, Sheila

doi:10.3389/fgene.2014.00119

Cited by 40 publications

(58 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data confirm our findings that documented association of resistance against S . mansoni and S. haematobium challenge infection with type 2 biased‐immunity. Accordingly, type 2 responses are fundamental for resistance against schistosome infection, not only for protection against the parasite‐related immune‐pathology .…”

Section: Discussionmentioning

confidence: 99%

Papain‐Based Vaccination Modulates Schistosoma mansoni Infection‐Induced Cytokine Signals

et al. 2016

View full text Add to dashboard Cite

We have previously shown that immunization of outbred rodents with cysteine peptidases-based vaccine elicited type 2-biased immune responses associated with consistent and reproducible protection against challenge Schistosoma mansoni. We herein start to elucidate the molecular basis of C57BL/6 mouse resistance to S. mansoni following treatment with the cysteine peptidase, papain. We evaluated the early cytokine signals delivered by epidermal, dermal, and draining lymph node cells of na€ ıve, and S. mansoni -infected mice treated 1 day earlier with 0 or 50 lg papain, or immunized twice with papain only (10 lg/ mouse), papain-free recombinant S. mansoni glyceraldehyde 3-phosphate dehydrogenase and 2-Cys peroxiredoxin peptide (10 and 15 lg/mouse, respectively = antigen Mix), or papain-adjuvanted antigen Mix. Schistosoma mansoni infection induced epidermal and lymph node cells to release type 1, type 2 and type 17 cytokines, known to counteract each other. Expectedly, humoral immune responses were negligible until patency. Papain pretreatment or papain-based vaccination diminished or shut off S. mansoni infection early induction of type 1, type 17 and type 2 cytokines except for thymic stromal lymphopoietin and programmed the immune system towards a polarized type 2 immune milieu, associated with highly significant (P < 0.005 -<0.0001) resistance to S. mansoni infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Papain‐Based Vaccination Modulates Schistosoma mansoni Infection‐Induced Cytokine Signals

et al. 2016

View full text Add to dashboard Cite

show abstract

“…mansoni cercariae [11, 13, 15]. Percent (%) change was evaluated by the formula: % change = [mean number in unimmunized infected controls–mean number in immunized infected animals / mean number in infected controls] × 100.…”

Section: Methodsmentioning

confidence: 99%

Protective immune responses against Schistosoma mansoni infection by immunization with functionally active gut-derived cysteine peptidases alone and in combination with glyceraldehyde 3-phosphate dehydrogenase

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundSchistosomiasis, a severe disease caused by parasites of the genus Schistosoma, is prevalent in 74 countries, affecting more than 250 million people, particularly children. We have previously shown that the Schistosoma mansoni gut-derived cysteine peptidase, cathepsin B1 (SmCB1), administered without adjuvant, elicits protection (>60%) against challenge infection of S. mansoni or S. haematobium in outbred, CD-1 mice. Here we compare the immunogenicity and protective potential of another gut-derived cysteine peptidase, S. mansoni cathepsin L3 (SmCL3), alone, and in combination with SmCB1. We also examined whether protective responses could be boosted by including a third non-peptidase schistosome secreted molecule, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH), with the two peptidases.Methodology/Principal findingsWhile adjuvant-free SmCB1 and SmCL3 induced type 2 polarized responses in CD-1 outbred mice those elicited by SmCL3 were far weaker than those induced by SmCB1. Nevertheless, both cysteine peptidases evoked highly significant (P < 0.005) reduction in challenge worm burden (54–65%) as well as worm egg counts and viability. A combination of SmCL3 and SmCB1 did not induce significantly stronger immune responses or higher protection than that achieved using each peptidase alone. However, when the two peptidases were combined with SG3PDH the levels of protection against challenge S. mansoni infection reached 70–76% and were accompanied by highly significant (P < 0.005) decreases in worm egg counts and viability. Similarly, high levels of protection were achieved in hamsters immunized with the cysteine peptidase/SG3PDH-based vaccine.Conclusions/SignificanceGut-derived cysteine peptidases are highly protective against schistosome challenge infection when administered subcutaneously without adjuvant to outbred CD-1 mice and hamsters, and can also act to enhance the efficacy of other schistosome antigens, such as SG3PDH. This cysteine peptidase-based vaccine should now be advanced to experiments in non-human primates and, if shown promise, progressed to Phase 1 safety trials in humans.

show abstract

“…However, Schistosomiasis continues to spread in many parts of the world, especially due to lack of sanitation and irrigation projects (Steinmann et al 2006). It is estimated that, each year, schistosomiasis afflicts up to 600 million people in 74 tropical and sub-tropical countries, predominantly in the developing world (El Ridi et al 2014). Among the five different schistosome species, Schistosoma mansoni is the most abundant one in Egypt (Helmy et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Impact of gold nanoparticles on brain of mice infected with Schistosoma mansoni

et al. 2015

View full text Add to dashboard Cite

Schistosomiasis is a condition characterized by high rates of morbidity and cognitive impairment. It afflicts many people in tropical and sub-tropical countries. Our study aimed to investigate the protective role of gold nanoparticles (GNPs) on the brain of mice infected with Schistosoma mansoni. Characterizations of GNPs were determined by using high-resolution transmission electron microscopy. Three doses of GNPs (0.25, 0.5, and 1.0 mg/kg body weight) were used to treat animals after S. mansoni infection. The infection induced impairments in histological picture as a result of schistosome infection resulting in a disturbance in the content of the brain neurotransmitters, norepinephrine (NE), and dopamine (DA). Also, the infection induced significant reduction in glutathione level; oppositely, the levels of nitric oxide and malondialdehyde were increased significantly. In addition, S. mansoni was able to disregulate the infected mice brain Cacnb4, Cabp4, Vdac3, Glrb, and Adam23 messenger RNA (mRNA). On the other hand, treatment of mice with GNPs could alleviate the histological impairments, the changes in the content of NE and DA, and the brain oxidative damage. Also, GNPs could regulate the gene expression due to S. mansoni infection. Generally, GNPs could decrease the neurooxidative stress and regulated the gene expression in the brain of infected mice. Consequently, our results revealed an anti-neuroschistosomal effect of GNPs in mice infected with S. mansoni.

show abstract

Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases

Cited by 40 publications

References 104 publications

Papain‐Based Vaccination Modulates Schistosoma mansoni Infection‐Induced Cytokine Signals

Papain‐Based Vaccination Modulates Schistosoma mansoni Infection‐Induced Cytokine Signals

Protective immune responses against Schistosoma mansoni infection by immunization with functionally active gut-derived cysteine peptidases alone and in combination with glyceraldehyde 3-phosphate dehydrogenase

Impact of gold nanoparticles on brain of mice infected with Schistosoma mansoni

Contact Info

Product

Resources

About