In-depth computational analysis of calcium-dependent protein kinase 3 of Toxoplasma gondii provides promising targets for vaccination

Purpose@#The Toxoplasma gondii calcium-dependent protein kinase-3 (CDPK3) is a key enzyme for parasite egress, control of calcium-dependent permeabilization in parasitophorous vacuole membrane and tissue cyst formation. In this study, we comprehensively explored the bioinformatics features of this protein to improve vaccine design against T. gondii. @*Materials and Methods@#Various web servers were employed for the analysis of physicochemical properties, post-translational modifications, localization in the subcellular milieu, secondary and tertiary structures, as well as B-cell, major histocompatibility complex (MHC)-binding and cytotoxic T-lymphocyte (CTL) epitopes. @*Results@#This protein was a 537 amino acid antigenic and non-allergenic molecule with a molecular weight of 60.42 kDa, a grand average of hydropathicity score of -0.508, and aliphatic index of 79.50. There exists 46.74% alpha helix, 12.48% extended strand, and 40.78% random coil in the secondary structure. Ramachandran plot of the refined model demonstrated 99.3%, 0.7%, and 0.0% of residues in the favored, allowed and outlier areas, respectively. Besides, various potential B-cell (continuous and conformational), MHC-binding and CTL epitopes were predicted for Toxoplasma CDPK3 protein. @*Conclusion@#This article provides a foundation for further investigations, and laid a theoretical basis for the development of an appropriate vaccine against T. gondii infection.

In-depth computational analysis of calcium-dependent protein kinase 3 of Toxoplasma gondii provides promising targets for vaccination

Purpose@#The Toxoplasma gondii calcium-dependent protein kinase-3 (CDPK3) is a key enzyme for parasite egress, control of calcium-dependent permeabilization in parasitophorous vacuole membrane and tissue cyst formation. In this study, we comprehensively explored the bioinformatics features of this protein to improve vaccine design against T. gondii. @*Materials and Methods@#Various web servers were employed for the analysis of physicochemical properties, post-translational modifications, localization in the subcellular milieu, secondary and tertiary structures, as well as B-cell, major histocompatibility complex (MHC)-binding and cytotoxic T-lymphocyte (CTL) epitopes. @*Results@#This protein was a 537 amino acid antigenic and non-allergenic molecule with a molecular weight of 60.42 kDa, a grand average of hydropathicity score of -0.508, and aliphatic index of 79.50. There exists 46.74% alpha helix, 12.48% extended strand, and 40.78% random coil in the secondary structure. Ramachandran plot of the refined model demonstrated 99.3%, 0.7%, and 0.0% of residues in the favored, allowed and outlier areas, respectively. Besides, various potential B-cell (continuous and conformational), MHC-binding and CTL epitopes were predicted for Toxoplasma CDPK3 protein. @*Conclusion@#This article provides a foundation for further investigations, and laid a theoretical basis for the development of an appropriate vaccine against T. gondii infection.

Molecular characterization of Echinococcus granulosus in paraffin-embedded human tissues from Southwest Iran

Objective: To investigate Echinococcus (E.) granulosus genotypes as the causative agents of hydatidosis in humans in the southwest of Iran (Khuzestan province). Methods: In this study, isolates of 80 archived human paraffin embedded hydatid cysts were collected from pathology laboratories in Ahvaz city, Khuzestan province. DNA was extracted and examined by nested-PCR of ribosomal DNA (rDNA) internal transcribed spacer 1 (ITS1), and PCR-RFLP. In addition, the sequences of fragments of genes coding for Cox space1 and NADH dehydrogenase 1 (ND1) were also examined. Results: Of the 80 paraffin samples, 44 (55.0%) were from the liver, 27 (33.8%) from the lung, and the rest from other organs. The amplified hydatid genomic DNA showed that the cysts were E. granulosus strains. The results of PCR-RFLP and sequencing analysis revealed the presence of G1 genotype (sheep strain) in all human isolates. Furthermore, no camel strain (G6) was detected among all samples in the regions studied. Conclusions: The molecular findings indicate that the predominant genotype involved in E. granulosus transmission in southwest of Iran is the common sheep strain (G1), which occurs in human populations. These results may have important implications for hydatid disease control in the studied areas.

Rhoptry antigens as Toxoplasma gondii vaccine target

Toxoplasmosis is a cosmopolitan zoonotic infection, caused by a unicellular protozoan parasite known as Toxoplasma gondii that belongs to the phylum Apicomplexa. It is estimated that over one-third of the world's population has been exposed and are latently infected with the parasite. In humans, toxoplasmosis is predominantly asymptomatic in immunocompetent persons, while among immunocompromised individuals may be cause severe and progressive complications with poor prognosis. Moreover, seronegative pregnant mothers are other risk groups for acquiring the infection. The life cycle of T. gondii is very complex, indicating the presence of a plurality of antigenic epitopes. Despite of great advances, recognize and construct novel vaccines for prevent and control of toxoplasmosis in both humans and animals is still remains a great challenge for researchers to select potential protein sequences as the ideal antigens. Notably, in several past years, constant efforts of researchers have made considerable advances to elucidate the different aspects of the cell and molecular biology of T. gondii mainly on microneme antigens, dense granule antigens, surface antigens, and rhoptry proteins (ROP). These attempts thereby provided great impetus to the present focus on vaccine development, according to the defined subcellular components of the parasite. Although, currently there is no commercial vaccine for use in humans. Among the main identified T. gondii antigens, ROPs appear as a putative vaccine candidate that are vital for invasion procedure as well as survival within host cells. Overall, it is estimated that they occupy about 1%–30% of the total parasite cell volume. In this review, we have summarized the recent progress of ROP-based vaccine development through various strategies from DNA vaccines, epitope or multi epitope-based vaccines, recombinant protein vaccines to vaccines based on live-attenuated vectors and prime-boost strategies in different mouse models.

A systematic review and meta-analysis of the prevalence of toxoplasmosis in hemodialysis patients in Iran / 한국역학회지

OBJECTIVES: Toxoplasmosis is a parasitic disease that occurs worldwide, with a wide range of complications in immunocompromised patients. This systematic review and meta-analysis was performed to evaluate the seroprevalence of Toxoplasma gondii among patients undergoing hemodialysis in Iran.METHODS: We searched English and Persian databases for studies reporting T. gondii seroprevalence in Iranian hemodialysis patients through December 31, 2017. Inclusion and exclusion criteria were applied.RESULTS: A total of 10 studies containing 1,865 participants (1,048 patients and 817 controls) met the eligibility criteria. ImmunoglobulinG (IgG) antibodies against T. gondii were found in 58% (95% confidence interval [CI], 46 to 70) of hemodialysis patients and 40% (95% CI, 31 to 50) of healthy controls, while immunoglobulin M (IgM) antibodies were found in 2% (95% CI, 0 to 6) of hemodialysis patients and 0% (95% CI, 0 to 1) of healthy controls. The meta-analysis showed that hemodialysis patients were significantly more likely to be seropositive for IgG (odds ratio [OR], 2.04; 95% CI, 1.54 to 2.70; p < 0.001) and IgM (OR, 2.53; 95% CI, 1.23 to 5.22; p < 0.001) antibodies against T. gondii infection than healthy individuals.CONCLUSIONS: The current study revealed a high prevalence of T. gondii infection in hemodialysis patients. Since hemodialysis patients are immunocompromised and T. gondii can cause serious clinical complications, we recommend that periodic screenings for T. gondii infection should be incorporated into the routine clinical care of these patients.

A systematic review and meta-analysis of the prevalence of toxoplasmosis in hemodialysis patients in Iran / 한국역학회지

OBJECTIVES@#Toxoplasmosis is a parasitic disease that occurs worldwide, with a wide range of complications in immunocompromised patients. This systematic review and meta-analysis was performed to evaluate the seroprevalence of Toxoplasma gondii among patients undergoing hemodialysis in Iran.@*METHODS@#We searched English and Persian databases for studies reporting T. gondii seroprevalence in Iranian hemodialysis patients through December 31, 2017. Inclusion and exclusion criteria were applied.@*RESULTS@#A total of 10 studies containing 1,865 participants (1,048 patients and 817 controls) met the eligibility criteria. ImmunoglobulinG (IgG) antibodies against T. gondii were found in 58% (95% confidence interval [CI], 46 to 70) of hemodialysis patients and 40% (95% CI, 31 to 50) of healthy controls, while immunoglobulin M (IgM) antibodies were found in 2% (95% CI, 0 to 6) of hemodialysis patients and 0% (95% CI, 0 to 1) of healthy controls. The meta-analysis showed that hemodialysis patients were significantly more likely to be seropositive for IgG (odds ratio [OR], 2.04; 95% CI, 1.54 to 2.70; p < 0.001) and IgM (OR, 2.53; 95% CI, 1.23 to 5.22; p < 0.001) antibodies against T. gondii infection than healthy individuals.@*CONCLUSIONS@#The current study revealed a high prevalence of T. gondii infection in hemodialysis patients. Since hemodialysis patients are immunocompromised and T. gondii can cause serious clinical complications, we recommend that periodic screenings for T. gondii infection should be incorporated into the routine clinical care of these patients.

A systematic review and meta-analysis of the prevalence of toxoplasmosis in hemodialysis patients in Iran / 한국역학회지

OBJECTIVES: Toxoplasmosis is a parasitic disease that occurs worldwide, with a wide range of complications in immunocompromised patients. This systematic review and meta-analysis was performed to evaluate the seroprevalence of Toxoplasma gondii among patients undergoing hemodialysis in Iran. METHODS: We searched English and Persian databases for studies reporting T. gondii seroprevalence in Iranian hemodialysis patients through December 31, 2017. Inclusion and exclusion criteria were applied. RESULTS: A total of 10 studies containing 1,865 participants (1,048 patients and 817 controls) met the eligibility criteria. Immunoglobulin G (IgG) antibodies against T. gondii were found in 58% (95% confidence interval [CI], 46 to 70) of hemodialysis patients and 40% (95% CI, 31 to 50) of healthy controls, while immunoglobulin M (IgM) antibodies were found in 2% (95% CI, 0 to 6) of hemodialysis patients and 0% (95% CI, 0 to 1) of healthy controls. The meta-analysis showed that hemodialysis patients were significantly more likely to be seropositive for IgG (odds ratio [OR], 2.04; 95% CI, 1.54 to 2.70; p < 0.001) and IgM (OR, 2.53; 95% CI, 1.23 to 5.22; p < 0.001) antibodies against T. gondii infection than healthy individuals. CONCLUSIONS: The current study revealed a high prevalence of T. gondii infection in hemodialysis patients. Since hemodialysis patients are immunocompromised and T. gondii can cause serious clinical complications, we recommend that periodic screenings for T. gondii infection should be incorporated into the routine clinical care of these patients.

Recent progress in microneme-based vaccines development against Toxoplasma gondii

Toxoplasmosis is a cosmopolitan zoonotic disease, which infect several warm-blooded mammals. More than one-third of the human population are seropositive worldwide. Due to the high seroprevalence of Toxoplasma gondii infection worldwide, the resulting clinical, mental, and economical complications, as well as incapability of current drugs in the elimination of parasites within tissue cysts, the development of a vaccine against T. gondii would be critical. In the past decades, valuable advances have been achieved in order to identification of vaccine candidates against T. gondii infection. Microneme proteins (MICs) secreted by the micronemes play a critical role in the initial stages of host cell invasion by parasites. In this review, we have summarized the recent progress for MIC-based vaccines development, such as DNA vaccines, recombinant protein vaccines, vaccines based on live-attenuated vectors, and prime-boost strategy in different mouse models. In conclusion, the use of live-attenuated vectors as vehicles to deliver and express the target gene and prime-boost regimens showed excellent outcomes in the development of vaccines against toxoplasmosis, which need more attention in the future studies.

Calcium-dependent protein kinases are potential targets for Toxoplasma gondii vaccine

Toxoplasma gondii belongs to the Apicomplexa phylum that caused a widespread zoonotic infection in wide range of intermediate hosts. Over one-third of the world's population are latently infected with T. gondii and carry it. The complex life cycle of T. gondii indicates the presence of a plurality of antigenic epitopes. During the recent years, continuous efforts of scientists have made precious advances to elucidate the different aspects of the cell and molecular biology of T. gondii. Despite of great progresses, the development of vaccine candidates for preventing of T. gondii infection in men and animals is still remains a challenge. The calcium-dependent protein kinases (CDPKs) belongs to the superfamily of kinases, which restricted to the apicomplexans, ciliates, and plants. It has been documented that they contribute several functions in the life cycle of T. gondii such as gliding motility, cell invasion, and egress as well as some other critical developmental processes. In current paper, we reviewed the recent progress concerning the development of CDPK-based vaccines against acute and chronic T. gondii.