Global distribution of Echinococcus granulosus genotypes in domestic and wild canids: a systematic review and meta-analysis.

The current systematic review and meta-analysis demonstrate the genotypic distribution of canine echinococcosis worldwide. Studies published from the inception until 21 May 2021 were screened, relevant articles were selected and the random-effect model was used to draw forest plots with 95% confidence intervals (CIs). Totally, 44 articles were included, mostly examined dogs (37 records), followed by wolf (8 records), jackal (7 records), fox (3 records), pump fox (3 records) and coyote (1 record). Echinococcus granulosus sensu stricto (G1­G3) and G6/7 cluster of Echinococcus canadensis were the most common genotypes among canids. Most studies were conducted in Asia and Europe with 17 and 15 datasets, respectively. Exclusively, Iran possessed the highest number of studies (10 records). Meta-analysis showed that the pooled molecular prevalence of echinococcosis was 33.82% (95% CI 24.50­43.83%). Also, the highest and lowest prevalence of canine echinococcosis was calculated for South America (66.03%; 95% CI 25.67­95.85%) and Europe (19.01%; 95% CI 9.95­30.16%). Additionally, there were statistically significant differences between the global prevalence of echinococcosis in canines and publication year, continent, country, sample type, host and molecular test. These findings will elevate our knowledge on the poorly known canine echinococcosis worldwide.

Multi-epitope vaccine expressed in Leishmania tarentolae confers protective immunity to Toxoplasma gondii in BALB/c mice.

Current study deals with a novel multi-epitope vaccine designed in silico and its confirmation experiments for potential efficacy in BALB/c mice. Major histocompatibility complex (MHC)-binding and B-cell binding epitopes of five Toxoplasma antigens (SAG1, ROP16, GRA12, MIC4 and M2AP) were predicted. Selected epitopes were fused together using SAPGTP linker, and antigenicity, allergenicity, physico-chemical features, secondary and tertiary structures and validations were all performed via bioinformatics servers. Then, vaccine construct was cloned into pLEXSY-neo 2.1 vector. After Leishmania tarentolae transfection, live recombinant and wild parasites were subcutaneously injected into 6-8 week female BALB/c mice and immune responses were measured. Results showed that the peptide possessed 282 amino acid residues with average molecular weight of 28.06 kDa. About 90% of the peptide residues were incorporated in favored and allowed regions of the Ramachandran plot. Vaccinated mice showed remarkably elevated levels of specific antibodies (P < 0.05) with predominance of IgG2a production. Also, a Th1 immune response with production of IFN-γ and relatively increased survival rate against intraperitoneal challenge with RH strain was demonstrated in immunized mice than control groups (P < 0.05). Also, very low levels of IL-4 were demonstrated, which showed statistically significant association with controls (P < 0.05). The findings clarified that multi-epitope vaccine expressed in Leishmania tarentolae induced significant immune responses against acute toxoplasmosis.

Global prevalence of Trichomonas vaginalis among female sex workers: a systematic review and meta-analysis.

Trichomoniasis is a sexually transmitted infection (STI), caused by the protozoan parasite, Trichomonas vaginalis. Female sex workers are intensely affected by the infection, since they have frequent direct physical contact. The current systematic review and meta-analysis represents the global prevalence of T. vaginalis in female sex workers. Five databases (Science Direct, Scopus, PubMed, Web of Science, and Google Scholar) were explored for literatures that published from July 1985 to June 2020. Totally, 85 studies (54,515 participants) from 46 countries met the inclusion criteria. The global pooled prevalence of T. vaginalis was 16% (95% CI 13-19%). The estimated pooled prevalence based on methods including wet mount, culture, and molecular techniques was 15% (95% CI 12-19%), 16% (95% CI 10-24%), and 22% (95% CI 13-32%), respectively. Moreover, the infection was most prevalent at the mean age of 30-36 (20%, 95% CI 11-30%). Regarding the World Health Organization (WHO) regions, the highest pooled prevalence was estimated to be in the African region (23%, 95% CI 7-46%). In addition, we indicated that countries with low-income level have the highest pooled prevalence (23%, 95% CI 14-34%). Our results revealed that the worldwide prevalence of T. vaginalis was significant in female sex workers. Therefore, considering a precise strategy such as a health education program with regard to safe intercourse is needed to increase knowledge and prevent T. vaginalis infection in sex workers.

Confirmed cases of human Onchocerca lupi infection: a systematic review of an emerging threat.

Diverse Onchocerca species are present mostly parasitizing ungulates, with the exception of Onchocerca volvulus (O. volvulus) in humans and O. lupi in canids and cats. The human cases due to the O. lupi have been more highlighted during last years. So, the present review was performed to determine the detailed characteristics of confirmed human O. lupi case reports documented worldwide. Hence, a systematic search was done using English international databases (Scopus, PubMed, Web of Science, Embase, ProQuest, and Google Scholar). Totally, 14 confirmed human cases were documented during the last decade, mostly from the USA and Turkey with 7 and 3 cases, respectively. Most cases (7 individuals) were male with the age range of 22-month-old to 54-year-old. The parasite was frequently isolated from the right eye (5 cases), followed by the left eye (4 cases), cervical spinal canal (3 cases), scalp, and right forearm (one case each). Molecular identification of the isolated agent was the preferred way of diagnosis in most cases (9 records). In conclusion, human O. lupi cases have been more highlighted in recent years, whether due to the improved diagnostics and/or host-switching phenomenon, and both veterinarians and healthcare authorities should be alerted.

Computational probing of Toxoplasma gondii major surface antigen 1 (SAG1) for enhanced vaccine design against toxoplasmosis.

The SAG1 is a tachyzoite-specific protein critical for Toxoplasma gondii (T. gondii) adhesion to surface receptors of the host cells. In this study we've comprehensively excavated the sequence of SAG1 using online bioinformatics servers toward better vaccine design against toxoplasmosis. Web-based tools were used to assess the physico-chemical properties, post-translational modifications (PTMs), transmembrane domains, subcellular localization, secondary and 3D structures, as well as B-cell, Cytotoxic T cells (CTL) and major histocompatibility complex (MHC) epitopes. The 336 amino acid sequence possessed a molecular weight of 34829.02 D, aliphatic index of 80.15 and GRAVY score of 0.129. There was 47 PTM sites without any transmembrane domains. Also, the SAG1 protein was appointed to be immunogen and non-allergen. The secondary structure comprised 62.5% random coil, 26.79% extended strand and 10.71% alpha helix. Ramachandran plot of the refined model demonstrated 94.4% residues in the favored region, 4.8% in allowed region and 0.8% in outlier region. Additionally, various potential B-cell (linear and conformational), CTL and HTL epitopes were predicted for T. gondii SAG1. This in silico investigation would be a premise for appropriate immunization strategies against toxoplasmosis. More studies are anticipated to be done empirically using SAG1 immunoprotective epitopes combined with other antigenic compounds.

Toxoplasma gondii ROP38 protein: Bioinformatics analysis for vaccine design improvement against toxoplasmosis.

Rhoptry proteins (ROPs) play a significant role in various stages of Toxoplasma gondii (T. gondii) life cycle, being critical for both invasion and intracellular survival. ROP38 is a key manipulator of host gene expression and has a function in tachyzoite to bradyzoite conversion. In this study, we've employed various bioinformatics online tools for immunogenicity prediction of ROP38 protein, comprising physico-chemical, antigenic and allergenic profiles, transmembrane domain, subcellular localization, post-translational modification (PTM) sites, secondary and 3D structure, B-cell, MHC-binding and cytotoxic T-lymphocyte (CTL) epitopes. The findings showed 54 PTM sites without a transmembrane domain. Also, ROP38 was proved a non-allergenic and antigenic protein. The protein had Sec signal peptide (Sec/SPI) with 0.8762 likelihood. The secondary structure included 52.68% random coil, 29.57% alpha helix and 17.74% extended strand. Based on Ramachandran plot output for refined model, 95.3%, 3.4%, and 1.4% of amino acid residues were incorporated in the favored, allowed, and outlier regions, respectively. B-cell epitopes TFPGDDIQTSS (67-72) and KAKNKWGRTRYTLQG (207-221) as well as T-cell epitope LSPVGFFTAL (6-15) possessed the highest antigenic index in the protein sequence. This paper is a premise for further researches, and provides insights for the development of a suitable vaccine against toxoplasmosis. More empirical studies are required using the ROP38 alone or in combination with other antigens/epitopes in the future.

Prevalence of Toxocara and Toxascaris infection among human and animals in Iran with meta-analysis approach.

BACKGROUND: Toxocariasis is a worldwide zoonotic parasitic disease caused by species of Toxocara and Toxascaris, common in dogs and cats. Herein, a meta-analysis was contrived to assess the prevalence of Toxocara/Toxascaris in carnivore and human hosts in different regions of Iran from April 1969 to June 2019. METHODS: The available online articles of English (PubMed, Science Direct, Scopus, and Ovid) and Persian (SID, Iran Medex, Magiran, and Iran Doc) databases and also the articles that presented in held parasitology congresses of Iran were involved. RESULTS: The weighted prevalence of Toxocara/Toxascaris in dogs (Canis familiaris) and cats (Felis catus) was 24.2% (95% CI: 18.0-31.0%) and 32.6% (95% CI: 22.6-43.4%), respectively. Also, pooled prevalence in jackal (Canis aureus) and red fox (Vulpes vulpes) was 23.3% (95% CI: 7.7-43.2%) and 69.4% (95% CI: 60.3-77.8%), correspondingly. Weighted mean prevalence of human cases with overall 28 records was 9.3% (95% CI: 6.3-13.1%). The weighted prevalence of Toxocara canis, Toxocara cati, and Toxascaris leonina was represented as 13.8% (95% CI: 9.8-18.3%), 28.5% (95% CI: 20-37.7%) and 14.3% (95% CI: 8.1-22.0%), respectively. CONCLUSION: Our meta-analysis results illustrate a considerable prevalence rate of Toxocara/Toxascaris, particularly in cats and dogs of northern parts of Iran. The presence of suitable animal hosts, optimum climate and close contact of humans and animals would have been the reason for higher seroprevalence rates of human cases in our region. Given the significance clinical outcomes of human Toxocara/Toxascaris, necessary measures should be taken.

Filarial worms: a systematic review and meta-analysis of diversity in animals from Iran with emphasis on human cases.

Current systematic review and meta-analysis demonstrate the prevalence reports of filariasis in animals in Iran along with human cases. Studies were screened, relevant papers were selected and the random-effect model was used by forest plot with 95% confidence interval (CI). Of 17 records of human case-reports, particularly from Khuzestan province (5 cases), Dirofilaria repens was the most detected parasite (10 cases) with higher involvement of the right eye (7 cases) than other organs. Eleven animal species were reported to be parasitised by filarioids in Iran. The prevalence of Dirofilaria immitis in canids was 14.69% (95% CI: 10.33-19.67), with highest rates (20.92%; 95% CI: 13.84-29.03) in free-ranging dogs. Male (10.07%; 95% CI: 5.10-16.47) and more than 1-year old (20.77%; 95% CI: 8.66-36.42) dogs were more likely to be found infected. The frequency of other filarioids of zoonotic interest was: Acanthocheilonema reconditum in dogs 2.15% (95% CI: 0.71-4.33), Dipetalonema evansi in camels 10.16% (95% CI: 4.73-17.34), Onchocerca cervicalis in horses 3.63% (95% CI: 1.44-6.75%) and Onchocerca fasciata 16.57% (95% CI: 10.12-24.24%) in camels. Still, our knowledge on parasitic filariae in Iran is limited and more investigation is needed in both human and animal populations.

Is there association between Trichomonas vaginalis infection and prostate cancer risk?: A systematic review and meta-analysis.

We performed a systematic review and meta-analysis to reveal the association between Trichomonas vaginalis (TV) infection and the risk of prostate cancer (PCa) development. Systematic searching (PubMed/Medline, Scopus, Embase, Web of Science, Cinhal, Wiley, Cochrane, Psychoinfo, ProQuest and Google Scholar) was done, up to March 2018 for case-control studies. Random effects model was applied to define odds ratios and their 95% confidence intervals. In total, 6 enteries were included in our meta-analysis, comprising 5590 individuals (2677 PCa cases and 2913 control individuals) examined for trichomoniasis, with a total positivity of 469 (17.51%) and 482 (16.54%) individuals, respectively. Totally, such association was documented in three countries, including USA (4 studies), Kuwait (one study) and Taiwan (one study). Based on pooled estimations, however a 1.17-time increase of PCa was observed among individuals with a previous exposure of TV, it was not statistically significant [OR = 1.17 (95% CI: 1.01 to 1.36)]. Egger's regression test demonstrated no publication bias among studies. Also, year of publication for included records was not significantly correlated to the relationship between trichomoniasis and PCa. Any further inferences should be based on future investigations for better understanding this relationship and shedding light on the cryptic pathogenesis of TV in PCa patients.

A systematic review and meta-analysis of the prevalence of Leishmania infection in blood donors.

BACKGROUND: The risk of transfusion transmitted leishmaniasis (TTL) from apparently healthy persons or asymptomatic individuals, should not be ignored. Lack of a comprehensive review, encouraged us to design a systematic review with meta-analysis approach to assess the prevalence of Leishmania infection in healthy blood donors. METHODS: For this purpose, 6 English databases (PubMed, Scopus, Web of Sciences, Science Direct, EMBASE and CINAHL) were browsed from January 1990 to July 2016. RESULTS: Due to significant heterogeneity, the random-effects model was used (I2=98.04% and 94.68%, for serological and molecular methods, respectively). A total of 496 papers were found through searching in which 17,816 apparently healthy blood donors were examined for Leishmania infection. The weighted overall prevalence of Leishmania infection in this group was estimated 4% (95% CI=2-7) and 8.7% (95% CI=4.2-14.3) using serological and molecular methods, respectively. CONCLUSIONS: High serological prevalence does not justify widespread donor screening. Leukodepletion filters would substantially decrease the risk of TTL, hence they are potentially proposed in endemic areas specifically for high-risk recipients. To better enlighten the epidemiological aspects of Leishmania infection in blood donors, it is suggested to perform high-level stewardship and more precise studies with regard to involved risk factors.

Toxoplasma gondii seroprevalence in the Iranian blood donors: A systematic review and meta-analysis.

Background: The present systematic review and meta-analysis was done to assess the rate of Toxoplasma gondii (T. gondii) exposure among Iranian healthy blood donors. Methods: We searched four English (PubMed, Scopus, Web of Science, and Science Direct) and two Persian databases (Magiran and SID) as well as Google Scholar as a specialized article search engine using specific keywords for relevant papers from the inception up to November 30, 2023. Results: In total, 19 studies enrolling 8226 apparently healthy blood donors were examined regarding T. gondii-specific IgG and/or IgM antibodies, among which 2666 [32.9% (95% CI: 25.3%-41.6%)], 168 [1.4% (95% CI: 0.9%-2.1%)], and 83 [1.7% (95% CI: 1.3%-2.1%)] subjects were seropositive regarding IgG, IgM, and both IgG/IgM antibodies, respectively. Five risk factors were significantly associated with T. gondii seroprevalence, including gender (OR = 1.98; 95% CI: 1.52-2.58; P < 0.001), contact with cat (OR = 2.41; 95% CI: 1.70-3.41; P < 0.001), contact with soil (OR = 2.83; 95% CI: 1.07-7.45; P = 0.035), consuming raw/undercooked meat (OR = 1.95; 95% CI: 1.03-3.70; P = 0.039), and raw/unwashed vegetables (OR = 1.70; 95% CI: 1.25-2.31; P = 0.001). Conclusion: A moderate rate of T. gondii exposure was found in the Iranian blood donors, with the association of several risk factors, including gender, contact with cat, contact with soil, consumption of unwashed vegetables and/or undercooked meat. Still, more studies are recommended regarding T. gondii exposure among blood donors in Iran.

In Silico Characterization of an Important Metacyclogenesis Marker in Leishmania donovani, HASPB1, as a Potential Vaccine Candidate.

Visceral leishmaniasis is a life-threatening infectious disease worldwide. Extensive experiments have been done to introduce potential vaccine candidates to combat leishmaniasis. The present study was done to evaluate Leishmania donovani hydrophilic acylated surface protein B1 as a potential vaccine candidate using in silico methods. For this aim, server-based predictions were performed regarding physicochemical characteristics, solubility, antigenicity, allergenicity, signal peptide, transmembrane domain, and posttranslational modifications (PTMs). Also, secondary and tertiary structures were predicted using NetSurfP-3.0 and I-TASSER, respectively. The 3D model was further subjected to refinement and validation, and promising B-cell, cytotoxic T-lymphocyte (CTL; human, dog), and helper T-lymphocyte (HTL; human) epitopes were predicted. The protein had a molecular weight of 42.19 kDa, with high solubility (0.749), stability (instability index: 21.34), and hydrophilicity (GRAVY: -2.322). No signal peptide or transmembrane domain was predicted, and the most abundant PTMs were phosphorylation, O-glycosylation, and acetylation. Many coils and disordered regions existed in the secondary structure analysis, and the tertiary model had a good confidence score (-0.79). Next, the ProSA-web and PROCHECK tools showed adequate improvements in the refined model compared to the crude model. Only 4 shared B-cell epitopes among three web servers (ABCpred, BepiPred 2.0, and SVMTriP) were shown to be antigenic, nonallergenic, and with good water solubility. Also, five potent CTL epitopes in dogs and five in humans were predicted. Notably, two HTL epitopes were found to be potential IFN-γ inducers. In conclusion, our results demonstrated several immunogenic epitopes in this protein, which could be directed towards multiepitope vaccine design.

In silico design of a novel peptide-based vaccine against the ubiquitous apicomplexan Toxoplasma gondii using surface antigens.

Human toxoplasmosis is a global public health concern and a commercial vaccine is still lacking. The present in silico study was done to design a novel vaccine candidate using tachyzoite-specific SAG1-realted sequence (SRS) proteins. Overlapping B-cell and strictly-chosen human MHC-I binding epitopes were predicted and connected together using appropriate spacers. Moreover, a TLR4 agonist, human high mobility group box protein 1 (HMGB1), and His-tag were added to the N- and C-terminus of the vaccine sequence. The final vaccine had 442 residues and a molecular weight of 47.71 kDa. Physico-chemical evaluation showed a soluble, highly antigenic and non-allergen protein, with coils and helices as secondary structures. The vaccine 3D model was predicted by ITASSER server, subsequently refined and was shown to possess significant interactions with human TLR4. As well, potent stimulation of cellular and humoral immunity was demonstrated upon chimeric vaccine injection. Finally, the outputs showed that this vaccine model possesses top antigenicity, which could provoke significant cell-mediated immune profile including IFN-γ, and can be utilized towards prophylactic purposes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00140-w.

Engineering and design of promising T-cell-based multi-epitope vaccine candidates against leishmaniasis.

Cutaneous leishmaniasis (CL) is a very common parasitic infection in subtropical areas worldwide. Throughout decades, there have been challenges in vaccine design and vaccination against CL. The present study introduced novel T-cell-based vaccine candidates containing IFN-γ Inducing epitopic fragments from Leishmania major (L. major) glycoprotein 46 (gp46), cathepsin L-like and B-like proteases, histone H2A, glucose-regulated protein 78 (grp78) and stress-inducible protein 1 (STI-1). For this aim, top-ranked human leukocyte antigen (HLA)-specific, IFN-γ Inducing, antigenic, CD4+ and CD8+ binders were highlighted. Four vaccine candidates were generated using different spacers (AAY, GPGPG, GDGDG) and adjuvants (RS-09 peptide, human IFN-γ, a combination of both, Mycobacterium tuberculosis Resuscitation promoting factor E (RpfE)). Based on the immune simulation profile, those with RS-09 peptide (Leish-App) and RpfE (Leish-Rpf) elicited robust immune responses and their tertiary structure were further refined. Also, molecular docking of the selected vaccine models with the human toll-like receptor 4 showed proper interactions, particularly for Leish-App, for which molecular dynamics simulations showed a stable connection with TLR-4. Upon codon optimization, both models were finally ligated into the pET28a( +) vector. In conclusion, two potent multi-epitope vaccine candidates were designed against CL and evaluated using comprehensive in silico methods, while further wet experiments are, also, recommended.

Neospora caninum SRS2 Protein: Essential Vaccination Targets and Biochemical Features for Next-Generation Vaccine Design.

Vaccination is a standout preventive measure to combat neosporosis among cattle herds. The present in silico study was done to evaluate the physicochemical properties and potent immunogenic epitopes of N. caninum SRS2 protein as a possible vaccine candidate. Web-based tools were used to predict physicochemical properties, antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, transmembrane domains and signal peptide, and secondary and tertiary structures as well as intrinsically disordered regions, followed by identification and screening of potential linear and conformational B-cell epitopes and those peptides having affinity to bind mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL). The protein had 401 residues with a molecular weight of 42 kDa, representing aliphatic index of 69.35 (thermotolerant) and GRAVY score of -0.294 (hydrophilic). There were 53 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly by extended strand, followed by helices and coils. The Ramachandran plot of the refined model showed 90.2%, 8.8%, 0.5%, and 0.5% residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B-cell (linear and conformational), CTL, and MHC-binding epitopes were predicted for N. caninum SRS2. These epitopes could be further utilized in the multiepitope vaccine constructs directed against neosporosis.

Determination of B and T Cell Epitopes in Neospora caninum Immune Mapped Protein-1 (IMP-1): Implications in Vaccine Design against Neosporosis.

Prevention of neosporosis is advantageous for cattle health and productivity. Previously, several vaccine candidates were nominated for vaccination against Neospora caninum. This study was premised on in silico evaluation of N. caninum IMP-1 in order to determine its physicochemical features and immunogenic epitopes. We employed a wide array of network-based tools for the prediction of antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, physicochemical properties, transmembrane domains and signal peptide, secondary and tertiary structures, and intrinsically disordered regions. Also, prediction and screening of potential continuous B cell peptides and those epitopes having stringent affinity to couple with mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL) receptors were accomplished. The protein had 393 residues with a molecular weight of 42.71 kDa, representing aliphatic index of 85.83 (thermotolerant) and GRAVY score of -0.447 (hydrophilic). There were 47 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly of extended strand and helices, followed by coils. The Ramachandran plot of the refined model showed 90.1%, 9.9%, 0.0%, and 0.0% residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B cell (linear and conformational), CTL, and MHC binding epitopes were predicted for N. caninum IMP-1. The findings of the present study could be further directed for next-generation vaccine design against neosporosis.

Co-infections of Schistosoma spp. and Malaria with Hepatitis Viruses from Endemic Countries: A Systematic Review and Meta-Analysis.

BACKGROUND: Co-infection of schistosomiasis and malaria with hepatitis B virus (HBV) and hepatitis C virus (HCV) are common in countries where schistosomiasis and malaria are endemic. OBJECTIVE: The present systematic review and meta-analysis was conducted to assess the prevalence of malaria/hepatitis viruses and Schistosoma/hepatitis viruses' co-infections. MATERIALS AND METHODS: Relevant published studies on the co-infection of malaria and Schistosoma spp. with HBV and HCV were retrieved via international databases (PubMed, Scopus, Web of Science, and Google Scholar). Regarding meta-analysis, the random-effect model was employed by forest plot with a 95% of confidence interval (CI). RESULTS: A total of 22 studies, including 15 studies with malaria/hepatitis viruses' co-infection and 7 studies with Schistosoma/hepatitis viruses' co-infection met the eligibility criteria. The co-infection of malaria/HCV and malaria/HBV in different populations were 15% (95% CI, 0-77%) and 5% (95% CI, 1-10%), respectively. Moreover, Schistosoma/HCV and Schistosoma/HBV co infection were detected in 7% (95% CI, 0-54%) and 2% (95% CI, 0-7%), respectively. CONCLUSION: The overlaps between Schistosoma spp. and malaria with hepatitis B and C viruses in endemic countries with lower income levels were high, which deserve further attention.

Towards the First Multiepitope Vaccine Candidate against Neospora caninum in Mouse Model: Immunoinformatic Standpoint.

Neospora caninum is an economically significant parasite among livestock, particularly in dairy cattle herds, causing storm abortions. Vaccination seems necessary to limit the infection and its harsh consequences. This is the first steps towards developing a multiepitope vaccine candidate against N. caninum using in silico approaches. High-ranked mouse MHC-binding and shared linear B-cell epitopes from six proteins (SRS2, MIC3, MIC6, GRA1, IMP-1, and profilin) as well as IFN-γ-inducing epitopes (from SAG1) were predicted, screened, and connected together through appropriate linkers. Finally, RS-09 protein (TLR4 agonist) and histidine tag were added to N- and C-terminal of the vaccine sequence, yielding 486 residues in length. Physicochemical properties showed a stable (instability index: 27.23), highly soluble, antigenic (VaxiJen score: 0.9554), and nonallergenic candidate. Secondary structure of the multiepitope protein included 58.85% random coil, 20.99% extended strand, and 20.16% alpha helix. Also, the tertiary structure was predicted, and further analyses validated a stable interaction between the vaccine model and mouse TLR4 (binding score: -1261.6). Virtual simulation of immune profile demonstrated potently stimulated humoral (IgG+IgM) and cell-mediated (IFN-γ) responses upon multiepitope vaccine injection. Altogether, a potentially immunogenic vaccine candidate was developed using several N. caninum proteins, with the capability to elicit IFN-γ upsurge and other components of cellular immunity, and can be used in prophylactic purposes against neosporosis.

Engineering a multi-epitope vaccine candidate against Leishmania infantum using comprehensive Immunoinformatics methods.

Visceral leishmaniasis (VL) is a severe disease with particular endemicity in over 80 countries worldwide. There is no approved human vaccine against VL in the market. This study was aimed at designing and evaluation of a multimeric vaccine candidate against Leishmania infantum through utilization of helper T lymphocyte (HTL) and cytotoxic T lymphocyte (CTL) immunodominant proteins from histone H1, KMP11, LACK and LeIF antigens. Top-ranked mouse MHC-I, MHC-II binders and CTL epitopes were predicted and joined together via spacers. Also, a TLR-4 agonist (RS-09 synthetic protein) and His-tag were added to the N- and C-terminal of the vaccine sequence, respectively. The final chimeric vaccine had a length of 184 amino acids with a molecular weight of 18.99 kDa. Physico-chemical features showed a soluble, highly-antigenic and non-allergenic candidate. Secondary and tertiary structures were predicted, and subsequent analyses confirmed the construct stability that was capable to properly interact with TLR-4/MD2 receptor. Immunoinformatics simulation displayed potent stimulation of T cell immune responses, with particular rise in IFN-γ, upon vaccination with the proposed multi-epitope candidate. In conclusion, immunoinformatics data demonstrated a highly antigenic vaccine candidate in mouse, which could develop considerable levels clearance mechanisms and other components of cellular immune profile, and can be directed for VL prophylactic purposes. Supplementary Information: The online version contains supplementary material available at 10.1007/s11756-021-00934-3.

Promising effects of parasite-derived compounds on tumor regression: a systematic review of in vitro and in vivo studies.

The parasites are repeatedly confronting their host to take advantage of nutrients for multiplication and survival. In this sense, a wide spectrum of molecules is released from both sides, with immune-regulatory activity, accompanying this biological battle. Such parasites and their valuable molecules can be directed toward microbial-based cancer therapy. Herein, we contrived a systematic review to gather information on the antitumor activity of parasite-derived compounds. Following systematic search in Web of Science, ScienceDirect, Scopus, PubMed, ProQuest and Embase until 31 December 2019, a total number of 51 articles (54 datasets) were finally included in this review. Thirteen parasitic agents were found to possess possible antitumor activity, comprising protozoan species Toxoplasma gondii, Trypanosoma cruzi, Trichomonas vaginalis, Acanthamoeba castellanii, Besnoitia jellisoni, Leishmania major, Plasmodium yoelii, and Plasmodium lophurae, as well as parasitic helminths Toxocara canis, Echinococcus granulosus, Taenia crassiceps, Trichinella spiralis, and Schistosoma mansoni. Most experiments were done based on antigenic preparations from T. gondii (16 studies), E. granulosus (10 studies), T. spiralis (8 studies), and T. cruzi (6 studies). Possible antitumor properties of the selected parasites were revealed in this review. However, precise molecular basis of anticancer activity for each parasite remains to be elucidated in the future.