Immunogenicity, antibody responses and vaccine efficacy of recombinant annexin B30 against Schistosoma mansoni.

AIMS: Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long-term protection of individuals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model. METHODS AND RESULTS: Bioinformatics analysis showed that there were three potential linear B-cell epitopes and four conformational B-cell epitopes predicted from annexin B30, respectively. Full-length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected. CONCLUSION: Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.

IgE antibodies from schistosomiasis patients to recognize epitopes in potato apyrase.

INTRODUCTION: High percentages of structural identity and cross-immunoreactivity have been reported between potato apyrase and Schistosoma mansoni ATP diphosphohydrolase (SmATPDases) isoforms, showing the existence of particular epitopes shared between these proteins. METHODS: Potato apyrase was employed using ELISA, western blot, and mouse immunization methods to verify IgE reactivity. RESULTS: Most of the schistosomiasis patient's (75%) serum was seropositive for potato apyrase and this protein was recognized using western blotting, suggesting that parasite and plant proteins share IgE-binding epitopes. C57BL/6 mice immunized with potato apyrase showed increased IgE antibody production. CONCLUSIONS: Potato apyrase and SmATPDases have IgE-binding epitopes.

IgE antibodies from schistosomiasis patients to recognize epitopes in potato apyrase

Abstract INTRODUCTION: High percentages of structural identity and cross-immunoreactivity have been reported between potato apyrase and Schistosoma mansoni ATP diphosphohydrolase (SmATPDases) isoforms, showing the existence of particular epitopes shared between these proteins. METHODS: Potato apyrase was employed using ELISA, western blot, and mouse immunization methods to verify IgE reactivity. RESULTS: Most of the schistosomiasis patient's (75%) serum was seropositive for potato apyrase and this protein was recognized using western blotting, suggesting that parasite and plant proteins share IgE-binding epitopes. C57BL/6 mice immunized with potato apyrase showed increased IgE antibody production. CONCLUSIONS: Potato apyrase and SmATPDases have IgE-binding epitopes.

Antigenic cross-reactivity between Schistosoma mansoni and pollen allergens from the birch tree (Betula verrucosa) and Timothy grass (Phleum pratense): involvement of shared glycan epitopes and implications for the hygiene hypothesis.

Previous studies have shown that schistosome infection can protect against allergic symptoms, but the underlying mechanisms are still not fully understood. Here we have shown that rabbit IgG antibodies raised against Schistosoma mansoni soluble egg antigens (SmSEA) are cross-reactive with a wide array of molecules in Timothy grass pollen (TGP) and birch tree pollen (BTP). Five of the cross-reactive pollen molecules (two from TGP and three from BTP) were selected randomly and identified by tandem mass spectrometric (TMS) analysis to be, respectively, the TGP allergens Phl p 1 and Phl p 5b, and BTP glutathione S-transferase (GST), and the BTP allergens Bet v 1 and Bet v 6.0102. Rabbit anti-SmSEA IgG antibodies that cross-reacted with each of the five allergens were found to be reactive with three major S. mansoni egg antigens, IPSE/alpha-1, omega-1 and kappa-5. Pairwise alignment of the amino acid sequences of each of the five TMS-identified pollen allergens with each of the three egg antigens revealed a low level of amino acid sequence identity. Further experiments indicated that the schistosome antigen/allergen cross-reactivity was mostly due to similar glycans present in helminths and plants, but not in mammals: so called cross-reactive carbohydrate determinants (CCDs). Previously, CCDs have been implicated in the cross-reactivity between many plants and invertebrates. Furthermore, pollen-induced anti-CCD IgGs have been found in sera of patients undergoing allergen-specific immunotherapy (SIT) and implicated in the treatment of the allergy. Thus, our finding provides not only possible explanations for the allergy-protective effect of helminth/schistosome infections as explained by the hygiene hypothesis, but also a potential starting point for improved SIT.

Rational selection of immunodominant and preserved epitope Sm043300e from Schistosoma mansoni and design of a chimeric molecule for biotechnological purposes.

Human schistosomiasis is a neglected tropical disease of great importance in public health. A large number of people are infected with schistosomiasis, making vaccine development and effective diagnosis important control strategies. A rational epitope prediction workflow using Schistosoma mansoni hypothetical proteins was previously presented by our group, and an improvement to that approach is presented here. Briefly, immunodominant epitopes from parasite membrane proteins were predicted by reverse vaccinology strategy with additional in silico analysis. Furthermore, epitope recognition was evaluated using sera of individuals infected with S. mansoni. The epitope that stood out in both in silico and in vitro assays was used to compose a rational chimeric molecule to improve immune response activation. Out of 2185 transmembrane proteins, four epitopes with high binding affinities for human and mouse MHCII molecules were selected through computational screening. These epitopes were synthesized to evaluate their ability to induce TCD4+ lymphocyte proliferation in mice. Sm204830e and Sm043300e induced significant TCD4+ proliferation. Both epitopes were submitted to enzyme-linked immunosorbent assay to evaluate their recognition by IgG antibodies from the sera of infected individuals, and epitope Sm043300 was significantly recognized in most sera samples. Epitope Sm043300 also showed good affinity for human MHCII molecules in molecular docking, and its sequence is curiously highly conserved in four S. mansoni proteins, all of which are described as G-protein-coupled receptors. In addition, we have demonstrated the feasibility of incorporating this epitope, which showed low similarity to human sequences, into a chimeric molecule. The stability of the molecule was evaluated by molecular modeling aimed at future molecule production for use in diagnosis and vaccination trials.

Immunological and parasitological parameters in Schistosoma mansoni-infected mice treated with crude extract from the leaves of Mentha x piperita L.

Schistosomiasis is a chronic disease caused by an intravascular trematode of the genus Schistosoma. Praziquantel is the drug used for treatment of schistosomiasis; nevertheless failure of treatment has been reported. Consequently, the identification of new effective schistosomicidal compounds is essential to ensure the effective control of schistosomiasis in the future. In this work we investigated the immunomodulatory and antiparasitic effects of the crude leaves extract of Mentha x piperita L. (peppermint) on murine Schistosomiasis mansoni. Female Balb/c mice were infected each with 50 S. mansoni cercariae and divided into three experimental groups: (I) untreated; (II) treated daily with M. x piperita L. (100mg/kg) and III) treated on 1/42/43 days post-infection with Praziquantel (500mg/kg). Another group with uninfected and untreated mice was used as a control. Subsequently, seven weeks post-infection, S. mansoni eggs were counted in the feces, liver and intestine. Worms were recovered by perfusion of the hepatic portal system and counted. Sera levels of IL-10, IL-5, IL-13, IFN-γ, IgG1, IgE and IgG2a were assayed by ELISA. Animals treated with a daily dose of M. x piperita L. showed increased sera levels of IL-10, IFN-γ, IgG2a and IgE. Besides, M. x piperita L. treatment promoted reduction in parasite burden by 35.2% and significant decrease in egg counts in the feces and intestine.

Failure of repeated treatment with praziquantel and arthemeter in four patients with acute schistosomiasis.

Schistosomiasis is on the rise but still difficult to treat in international travelers; it should be suspected in patients returning from endemic areas. Praziquantel (PZQ) is not effective and may aggravate symptoms. More recently, combination treatment with artemisinin derivatives have shown promising results. We report four cases of acute schistosomiasis (AS) in which several courses of combined therapy had been necessary to obtain negative serology.

Immunomodulatory effect of the alkaloidic extract of Solanum lycocarpum fruits in mice infected with Schistosoma mansoni.

Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma; it accounts for more than 280,000 deaths annually. In this work we investigated the effect of the alkaloidic extract obtained by acid-base extraction of the dried fruits of Solanum lycocarpum on schistosomiasis. We used this extract at concentrations of 10, 20, and 40 mg/kg to treat mice infected with Schistosoma mansoni in different phases of the parasite cycle, and we compared its effect with that of the positive control praziquantel (60 mg/kg). We evaluated the results on the basis of the number of macrophages, eggs, and granulomas; we also assessed nitric oxide (NO) and interferon-gamma (IFN-γ) production. Animals treated with a daily dose of 10 or 20 mg/kg alkaloidic extract between the 37th and 41st day of infection showed increased number of macrophages, elevated NO and IFN-γ concentrations, and reduced number of eggs and granulomas in the liver. The alkaloidic extract of S. lycocarpum fruits displayed an immunomodulatory effect on mice infected with S. mansoni, so its potential to treat schistosomiasis deserves further studies.

Characterization of a truncated metabotropic glutamate receptor in a primitive metazoan, the parasitic flatworm Schistosoma mansoni.

A novel glutamate-binding protein was identified in Schistosoma mansoni. The protein (SmGBP) is related to metabotropic glutamate receptors from other species and has a predicted glutamate binding site located within a Venus Flytrap module but it lacks the heptahelical transmembrane segment that normally characterizes these receptors. The SmGBP cDNA was cloned, verified by 5' and 3' Rapid Amplification of cDNA Ends (RACE) and shown to be polyadenylated at the 3'end, suggesting the transcript is full-length. The cloned cDNA was subsequently expressed in bacteria and shown to encode a functional glutamate-binding protein. Other studies, using a specific peptide antibody, determined that SmGBP exists in two forms, a monomer of the expected size and a stable but non-covalent dimer. The monomer and dimer are both present in the membrane fraction of S. mansoni and are resistant to extraction with high-salt, alkaline pH and urea, suggesting SmGBP is either an integral membrane protein or a peripheral protein that is tightly associated with the membrane. Surface biotinylation experiments combined with western blot analyses and confocal immunolocalization revealed that SmGBP localized to the surface membranes of adult male schistosomes, especially the dorsal tubercles. In contrast, we detected little or no expression of SmGBP either in the females or larval stages. A comparative quantitative PCR analysis confirmed that the level of SmGBP expression is several-fold higher in male worms than cercariae, and it is barely detectable in adult females. Together, the results identify SmGBP as a new type of schistosome glutamate receptor that is both gender- and stage-specific. The high-level expression of this protein in the male tubercles suggests a possible role in host-parasite interaction.

Detection of IgG1 and IgG4 subtypes reactive against potato apyrase in schistosomiasis patients.

In this paper, we showed for the first time that the conserved domains within Schistosoma mansoni ATP diphosphohydrolase isoforms, shared with potato apyrase, possess epitopes for the IgG1 and IgG4 subtypes, as 24 (80%) of the 30 schistosomiasis patients were seropositive for this vegetable protein. The analyses for each patient cured (n = 14) after treatment (AT) with praziquantel revealed variable IgG1 and IgG4 reactivity against potato apyrase. Different antigenic epitopes shared between the vegetable and parasite proteins could be involved in susceptibility or resistance to S. mansoni AT with praziquantel and these possibilities should be explored.

Antibody reactivity against potato apyrase, a protein that shares epitopes with Schistosoma mansoni ATP diphosphohydrolase isoforms, in acute and chronically infected mice, after chemotherapy and reinfection.

Schistosoma mansoni ATP diphosphohydrolase isoforms and potato apyrase share conserved epitopes. By enzyme-linked immunosorbent assays, elevated levels of IgM, IgG2a and IgG1 antibody reactivity against potato apyrase were observed in S. mansoni-infected BALB/c mice during the acute phase of infection, while only IgM and IgG1 antibody reactivity levels maintained elevated during the chronic phase of infection. Antibody reactivity against potato apyrase was monitored over an 11-month period in chronically-infected mice treated with oxamniquine. Eleven months later, the level of seropositive IgM decreased significantly (approximately 30%) compared to the level found in untreated, infected mice. The level of seropositive IgG1 decreased significantly four months after treatment (MAT) (61%) and remained at this level even after 11 months. The IgG2a reactivity against potato apyrase, although unchanged during chronic phase to 11 MAT, appeared elevated again in re-infected mice suggesting a response similar to that found during the acute phase. BALB/c mouse polyclonal anti-potato apyrase IgG reacted with soluble egg antigens probably due to the recognition of parasite ATP diphosphohydrolase. This study, for the first time, showed that the IgG2a antibody from S. mansoni-infected BALB mice cross-reacts with potato apyrase and the level of IgG2a in infected mice differentiates disease phases. The results also suggest that different conserved-epitopes contribute to the immune response in schistosomiasis.

Protective effects of Sm-p80 in the presence of resiquimod as an adjuvant against challenge infection with Schistosoma mansoni in mice.

OBJECTIVES: To determine the prophylactic efficacy of an Sm-p80-based vaccine formulation against challenge infection with Schistosoma mansoni in mice using an approach comprising of initial priming with DNA and boosting with recombinant protein in the presence of resiquimod (R848) as an adjuvant. METHODS: In the first experiment (prime-boost approach), mice were primed with Sm-p80-pcDNA3 (week 0) and boosted at weeks 4 and 8 with recombinant Sm-p80 formulated in resiquimod (R848). Each mouse in the control group first received only pcDNA3 and was boosted with R848. In the second set of experiments (recombinant protein approach), mice were immunized (week 0) and boosted (weeks 4 and 8) with rSm-p80 formulated in R848. Animals of the control group in this series of experiments received only R848 at 0, 4, and 8 weeks. All of the animals from both the 'prime-boost' and 'recombinant protein' groups were challenged with cercariae of S. mansoni, 4 weeks after the last immunization. The mice were sacrificed 6 weeks post-challenge and the reductions in worm burden and egg production were determined. Sm-p80-specific antibody titers were estimated in the mice sera by ELISA. Cytokine mRNA and protein production by proliferating splenocytes in response to in vitro stimulation with Sm-p80, were estimated via RT-PCR and ELISA, respectively. RESULTS: Vaccination with Sm-p80 (prime-boost approach) showed 49% reduction in worm burden; with the recombinant protein approach the protection was found to be 50%. The protection levels were correlated with antibody production. Upon antigenic stimulation with recombinant Sm-p80, splenocytes secreted significant levels of interferon (IFN)-γ and interleukin (IL)-2, indicating that the immune responses were Th1-biased and this was further supported in terms of distribution of antibody isotypes and mRNA expression of cytokines. CONCLUSIONS: In conclusion the present study clearly demonstrates that Sm-p80 consistently maintained its protective nature, and resiquimod as an immunopotentiating agent slightly boosted the protective effects of Sm-p80 in both 'DNA prime-protein boost' and 'recombinant protein' immunization approaches in a murine model.

Detection of IgG1 and IgG4 subtypes reactive against potato apyrase in schistosomiasis patients

In this paper, we showed for the first time that the conserved domains within Schistosoma mansoni ATP diphosphohydrolase isoforms, shared with potato apyrase, possess epitopes for the IgG1 and IgG4 subtypes, as 24 (80 percent) of the 30 schistosomiasis patients were seropositive for this vegetable protein. The analyses for each patient cured (n = 14) after treatment (AT) with praziquantel revealed variable IgG1 and IgG4 reactivity against potato apyrase. Different antigenic epitopes shared between the vegetable and parasite proteins could be involved in susceptibility or resistance to S. mansoni AT with praziquantel and these possibilities should be explored.

Antibody reactivity against potato apyrase, a protein that shares epitopes with Schistosoma mansoni ATP diphosphohydrolase isoforms, in acute and chronically infected mice, after chemotherapy and reinfection

Schistosoma mansoni ATP diphosphohydrolase isoforms and potato apyrase share conserved epitopes. By enzyme-linked immunosorbent assays, elevated levels of IgM, IgG2a and IgG1 antibody reactivity against potato apyrase were observed in S. mansoni-infected BALB/c mice during the acute phase of infection, while only IgM and IgG1 antibody reactivity levels maintained elevated during the chronic phase of infection. Antibody reactivity against potato apyrase was monitored over an 11-month period in chronically-infected mice treated with oxamniquine. Eleven months later, the level of seropositive IgM decreased significantly (~30 percent) compared to the level found in untreated, infected mice. The level of seropositive IgG1 decreased significantly four months after treatment (MAT) (61 percent) and remained at this level even after 11 months. The IgG2a reactivity against potato apyrase, although unchanged during chronic phase to 11 MAT, appeared elevated again in re-infected mice suggesting a response similar to that found during the acute phase. BALB/c mouse polyclonal anti-potato apyrase IgG reacted with soluble egg antigens probably due to the recognition of parasite ATP diphosphohydrolase. This study, for the first time, showed that the IgG2a antibody from S. mansoni-infected BALB mice cross-reacts with potato apyrase and the level of IgG2a in infected mice differentiates disease phases. The results also suggest that different conserved-epitopes contribute to the immune response in schistosomiasis.

Using poly-N-acetyl glucosamine gel matrix to deliver IL-12 with anti-schistosomasis vaccination.

BACKGROUND: Interleukin (IL)-12 is a potential adjuvant in a variety of diseases including schistosomiasis. The clinical use of IL-12, however, is limited by the toxicity associated with its systemic administration. We have developed a novel delivery system (designated F2 gel matrix) composed of poly-N-acetyl glucosamine that has the dual properties of sustaining the release of proteins (e.g. interleukins) and adjuvant effects. The main aim of this study was to use a mouse model to test whether IL-12 released from F2 gel can induce adjuvant effects in the schistosomiasis setting as compared to those obtained after systemic delivery of IL-12. METHODOLOGY: First, we compared the toxicity induced by paracrine (delivered by F2 gel) and systemic IL-12. Second, we compared the induction of cytokines induced by paracrine and systemic IL-12. Third, we compared the adjuvant effects of paracrine and systemic IL-12-based prophylactic vaccination against schistosomiasis using soluble worm antigen preparation (SWAP). RESULTS: IL-12 released from F2 gel did not induce significant toxicity measured by alanine aminotransferase (ALT). We found similar serum levels of IFN-gamma, TNF-alpha and IL-2 after paracrine and systemic IL-12 treatments. We also found that vaccination with F2 gel/SWAP/IL-12 induced higher anti-schistosomal effects than IL-12/SWAP as evidenced by 1) the decrease in the total liver egg counts; 2) the reduction in the granuloma size and fibrotic reaction in the liver; and 3) the amelioration of the liver functions. CONCLUSION: Collectively, these results indicate that IL-12-F2 gel delivery approach could be considered as a potential strategy for the treatment of schistosomiasis.

Immunostimulatory effects of extract of Pulicaria crispa before and after Schistosoma mansoni infection.

The immunostimulatory effects of methanolic extract from Pulicaria crispa were investigated in mice before and after infection with Schistosoma mansoni. Mice were subjected for daily intra-peritoneal injection by the extract (33 ng/mouse) for 10 successive days followed by infecting every mouse with 100 S. mansoni cercariae. Treatment with the extract induced significant increase (p < 0.05) in sera-IL-2 before and after infection. Upon using soluble worm antigen preparation or cancer bladder homogenates as antigens in ELISA, the detected levels of IgG were significantly (p < 0.05) higher in sera from treated-infected mice than untreated P. crispa infected mice. Using crude Escherichia coli lysate as an antigen in ELISA, it was detected a significant (p < 0.05) increase in IgG levels in sera from the extract-treated mice before and after infection.

Immunomodulatory effects of curcumin treatment on murine schistosomiasis mansoni.

Curcumin is a polyphenol derived from the dietary spice turmeric. It has been shown to regulate numerous transcription factors, cytokines, adhesion molecules, and enzymes that have been linked to inflammation. In addition to inhibiting the growth of a variety of pathogens, curcumin has been shown to have nematocidal activity. The present study was designed to evaluate the schistosomicidal activity of curcumin in vivo as well as immunomodulation of granulomatous inflammation and liver pathology in acute schistosomiasis mansoni. Mice were infected each with 80 Schistosoma (S.) mansoni cercariae and injected intraperitoneally with curcumin at a total dose of 400mg/kg body weight. Curcumin was effective in reducing worm and tissue-egg burdens, hepatic granuloma volume and liver collagen content by 44.4%, 30.9%, 79%, and 38.6%, respectively. Curcumin treatment restored hepatic enzymes activities to the normal levels and enhanced catalase activity in the liver tissue of infected mice. Moreover, hepato-spleenomegaly and eosinophilia induced by S. mansoni infection were largely improved with curcumin treatment. Infected mice treated with curcumin showed low serum level of both interleukin (IL)-12 and tumor necrosis factor alpha (TNF-alpha), but IL-10 level was not significantly altered. Specific IgG and IgG1 responses against both soluble worm antigen (SWAP) and soluble egg antigen (SEA) were augmented with curcumin treatment, but IgM and IgG2a responses were not significantly changed. In conclusion, curcumin treatment modulates cellular and humoral immune responses of infected mice and lead to a significant reduction of parasite burden and liver pathology in acute murine schistosomiasis mansoni.

Mapping of the conserved antigenic domains shared between potato apyrase and parasite ATP diphosphohydrolases: potential application in human parasitic diseases.

Evolutionary and closer structural relationships are demonstrated by phylogenetic analysis, peptide prediction and molecular modelling between Solanum tuberosum apyrase, Schistosoma mansoni SmATPase 2 and Leishmania braziliensis NDPase. Specific protein domains are suggested to be potentially involved in the immune response, and also seem to be conserved during host and parasite co-evolution. Significant IgG antibody reactivity was observed in sera from patients with American cutaneous leishmaniasis (ACL) and schistosomiasis using potato apyrase as antigen in ELISA. S. mansoni adult worm or egg, L. braziliensis promastigote (Lb) and Trypanosoma cruzi epimastigote (EPI) have ATP diphosphohydrolases, and antigenic preparations of them were evaluated. In ACL patients, IgG seropositivity was about 43% and 90% for Lb and potato apyrase, respectively, while IgM was lower (40%) or IgG (100%) seropositivity for both soluble egg (SEA) and adult worm (SWAP) antigens was higher than that found for potato apyrase (IgM=10%; IgG=39%). In Chagas disease, IgG seropositivity for EPI and potato apyrase was 97% and 17%, respectively, while the IgM was low (3%) for both antigens. The study of the conserved domains from both parasite proteins and potato apyrase could lead to the development of new drug targets or molecular markers.

Schistosoma mansoni: melatonin enhances efficacy of cercarial and soluble worm antigens in the induction of protective immunity against infection in the hamster.

Based on the beneficial influence of melatonin administration on the course of schistosomiasis and on its possible action on the immune system, we aimed in this study to establish an immunization program using Schistosoma mansoni adult worm antigen (SWAP) and cercarial antigen (CAP) alone or concurrently with melatonin treatment, for 30 successive days, in an attempt to enhance their efficacy against the infection in hamsters. Results showed that the worm reduction percentages were 53.8%, 67.01%, 56.4% and 99.3% for CAP, CAP+melatonin, SWAP, SWAP+melatonin, respectively, indicating that melatonin enhanced efficacy of SWAP but only produced a slight increase in efficacy of CAP. Highly significant reductions in egg load in the liver and alteration in the oogram pattern with a high percentage of immature eggs and few dead eggs were recorded in the groups that received melatonin treatment suggesting a possible role for melatonin in the regulation of egg production and development. On the other hand, melatonin clearly improved the oxidative status in the immunized groups. No antibody (Ab) response was recorded in the groups immunized with SWAP+melatonin while low Ab level was seen in the other melatonin-treated group. In addition to the antioxidant properties of melatonin, our results suggested that the early and continuous melatonin administration may result in immunomodulatory actions which in turn enhanced the efficacy of SWAP and CAP in different ways. This indicates the importance of further investigation of the mechanisms of melatonin action and the possible application in a vaccination program.

Cross-immunoreactivity between anti-potato apyrase antibodies and mammalian ATP diphosphohydrolases: potential use of the vegetal protein in experimental schistosomiasis

We have previously showed that Schistosoma mansoni ATP-diphosphohydrolase and Solanum tuberosum potato apyrase share epitopes and the vegetable protein has immunostimulatory properties. Here, it was verified the in situ cross-immunoreactivity between mice NTPDases and anti-potato apyrase antibodies produced in rabbits, using confocal microscopy. Liver samples were taken from Swiss Webster mouse 8 weeks after infection with S. mansoni cercariae, and anti-potato apyrase and TRITC-conjugated anti-rabbit IgG antibody were tested on cryostat sections. The results showed that S. mansoni egg ATP diphosphohydrolase isoforms, developed by anti-potato apyrase, are expressed in miracidial and egg structures, and not in granulomatous cells and hepatic structures (hepatocytes, bile ducts, and blood vessels). Therefore, purified potato apyrase when inoculated in rabbit generates polyclonal sera containing anti-apyrase antibodies that are capable of recognizing specifically S. mansoni ATP diphosphohydrolase epitopes, but not proteins from mammalian tissues, suggesting that autoantibodies are not induced during potato apyrase immunization. A phylogenetic tree obtained for the NTPDase family showed that potato apyrase had lower homology with mammalian NTPDases 1-4, 7, and 8. Further analysis of potato apyrase epitopes could implement their potential use in schistosomiasis experimental models.