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Rashidi, S.;  Sánchez-Montejo, J.;  Mansouri, R.;  Ali-Hassanzadeh, M.;  Savardashtaki, A.;  Bahreini, M.S.;  Karimazar, M.;  Manzano-Román, R.;  Nguewa, P. Toxoplasma gondii. Toxoplasmosis. Encyclopedia. Available online: https://encyclopedia.pub/entry/25346 (accessed on 02 July 2024).
Rashidi S,  Sánchez-Montejo J,  Mansouri R,  Ali-Hassanzadeh M,  Savardashtaki A,  Bahreini MS, et al. Toxoplasma gondii. Toxoplasmosis. Encyclopedia. Available at: https://encyclopedia.pub/entry/25346. Accessed July 02, 2024.
Rashidi, Sajad, Javier Sánchez-Montejo, Reza Mansouri, Mohammad Ali-Hassanzadeh, Amir Savardashtaki, Mohammad Saleh Bahreini, Mohammadreza Karimazar, Raúl Manzano-Román, Paul Nguewa. "Toxoplasma gondii. Toxoplasmosis" Encyclopedia, https://encyclopedia.pub/entry/25346 (accessed July 02, 2024).
Rashidi, S.,  Sánchez-Montejo, J.,  Mansouri, R.,  Ali-Hassanzadeh, M.,  Savardashtaki, A.,  Bahreini, M.S.,  Karimazar, M.,  Manzano-Román, R., & Nguewa, P. (2022, July 20). Toxoplasma gondii. Toxoplasmosis. In Encyclopedia. https://encyclopedia.pub/entry/25346
Rashidi, Sajad, et al. "Toxoplasma gondii. Toxoplasmosis." Encyclopedia. Web. 20 July, 2022.
Toxoplasma gondii. Toxoplasmosis
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This entry is adapted from the peer-reviewed paper 10.3390/ani12091098

Toxoplasma gondii is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts leading to an infectious zoonotic disease known as toxoplasmosis. The infection outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. 

Toxoplasma gondii toxoplasmosis Parasite

1. Introduction. Vaccine and Diagnostic Strategies in Toxoplasmosis

Toxoplasma gondii, the causative agent of toxoplasmosis, is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts [1]. Toxoplasmosis affects approximately one-third of the world’s human population but also may be a concern in a considerable number of mammalian and avian species, with potential associated public health risks [2][3][4]. Although toxoplasmosis is usually asymptomatic in immune-competent individuals, the outcomes of infection could be severe or fatal in patients with immunodeficiency, diabetes patients, and pregnant women and infants [5][6][7]. The One Health approach to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. Therefore, the development of effective vaccine and diagnostics strategies is urgent for the elimination of this infection.
The immunological effects of numerous vaccination trials, including attenuated and inactivated vaccines, genetically engineered vaccines, subunit vaccines, and DNA vaccines, have been evaluated and developed against toxoplasmosis in animal models. However, such strategies have also encountered several difficulties, such as vaccine construct, routes of administration, and standardization of immunization evaluation [8].
Live attenuated vaccines are more likely to produce the beneficial T helper (Th1) immune response compared to the subunit or DNA vaccines in different infectious agents, especially in intracellular pathogens. However, there are a limited number of trials evaluating concerns of such vaccines, maybe due to their reversion of attenuated pathogens to their virulent form [9][10]. Therefore, whole genome sequencing and appealing strategies, including clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, to edit genes of Toxoplasma parasites and the construction of novel mutant strains have recently accelerated the improvement of live attenuated vaccines against toxoplasmosis. Thus, a huge range of experimental live-attenuated vaccines were described through deleting or knocking-out numerous genes [11][12]. Recently, a wide range of DNA vaccines against toxoplasmosis have been developed. The efficacy of such vaccines is deeply affected by the method of vaccine delivery. Furthermore, it has been suggested that DNA vaccines expressing several antigens could further induce protection against toxoplasmosis than single antigen vaccines [11]. Similarly, numerous candidate proteins involved in the Toxoplasma parasite pathogenesis, survival, and relevant critical pathways to this infection, have been employed as vaccine antigens in recombinant subunit vaccines. In this sense, the protective efficacy of multi-antigenic subunit vaccines has been underlined [11].
Some of the Toxoplasma proteins, such as calcium-dependent protein kinases (CDPKs), have been targeted as vaccine candidates against toxoplasmosis by using the abovementioned strategies. It has been indicated that the use of CDPK1, CDPK2 and CDPK3 in the form of attenuated, recombinant and DNA vaccine induced high levels of Th1-associated cytokines, and prolonged survival and decrease brain cysts in vaccinated mice [13][14][15][16][17]. In addition, in silico tools have predicted recently potential immunogenic B- and T-cell epitopes for CDPK4 and CDPK7, pointing out their potential as appropriate vaccine candidates against T. gondii [18][19].
Despite of all those approaches, there is currently no licensed toxoplasmosis vaccine available for humans. “Toxovax” is considered as the only commercial vaccine (designed based on live attenuated (S48 strain) strategy) against congenital toxoplasmosis in ewes. The use of such vaccines for humans needs to overcome big challenges, such as their high cost, adverse effects, short shelf-life, and the risk of reverting to a virulent form.
On the other hand, different serodiagnostic tests have been expanded for the detection of human toxoplasmosis. As a recent strategy, the use of recombinant proteins or a combination of several recombinant proteins have been successfully suggested for measuring T. gondii antibodies at different stages of this infection. However, the development of relatively rapid, highly sensitive and specific methods has remained a prominent challenge in this sense. Therefore, integrating genomic, transcriptomic, and proteomic tools and multilocus genotyping methods with molecular and bioinformatics techniques have been currently suggested to increase the sensitivity and specificity of the diagnostic methods based on the use of recombinant proteins [20].

2. Toxoplasma Life Cycle Stages. Proteome and Proteomics

The different T. gondii life stages employ specific mechanisms for triggering stage conversion, and these could be related to pathobiology within the host [21]. Changes in the expression levels of some proteins also occur as parasites progress through their life cycles, and it is likely that particular proteins have important functions in restricted life stages [22]. Since most of such proteins are involved in the parasite survival, virulence and modulation of the host immune response, the identification and biological understanding of these critical proteins in the different parasitic forms might be useful for the diagnosis, directed targeting and prevention of the disease (vaccination). Accordingly, further improvements of the effective serodiagnostic tools and the potentiality of vaccine candidates in inducing the host immune responses are considered key factors for the discovery of new functionality relevant proteins in the Toxoplasma (life cycle stages) proteome [3].
Some of the differentially expressed proteins in each stage of the Toxoplasma parasite’s life cycle could be correlated with the pathogenesis or might induce host immune responses. Thus, the use of such a common immunodominant protein expressed in all stages or the selection of several immunodominant proteins in all stages as a multistage (multivalent) vaccine could efficiently induce the desired immune responses during all stages of the parasite. On the other hand, designed vaccines based on a multistage strategy are able to exhibit efficient effects in initial and recurrent infections and probably exert major functions in restricting the bradyzoites released from tissue cysts [23]. Due to the active functions of proteins, such as Toxoplasma dense granule antigen 1 (TgGRA1) and bradyzoite antigen 1 (BAG1), during the invasion of host cell and their potential to induce increased immunoglobulin G (IgG) levels (with slight tendency to IgG2a response) and interferon gamma (IFN-γ) secreting cluster of differentiation 4 (CD4) and CD8 cells, these proteins were described as vaccine candidates to generate a multistage vaccine which could block the tachyzoite and bradyzoite stages of the parasite [24]. A common immunodominant protein, such as microneme protein 3 (MIC3), that could be expressed as a critical protein in the proteome of Toxoplasma-oocysts [22], Toxoplasma-tachyzoites (excretory-secretory antigens (ESAs) and soluble tachyzoite antigens (STAgs)) [25][26] might also be a potential multistage vaccine against toxoplasmosis. Evidence has shown that MIC3, 4, 13, rhoptry neck protein 5 (RON5), rhoptry protein 2 (ROP2), and GRA1, 6, 8, 14 with potential pathogenicity and immunogenicity properties were expressed in the three infective stages of Toxoplasma parasites. Moreover, other potential virulent and immunodominant proteins, including rhomboid 4 (ROM4), ROP5, 16, 17, 38, GRA2, 4, 15, 10, 12, 16, RON4, MIC1, 5, and surface antigen 3 (SAG3), were identified only in tachyzoites and bradyzoites stages [23]. These proteins could also be considered in multistage vaccine against toxoplasmosis.
Proteomics analysis has allowed the identification of key proteins that can be utilized in the development of novel disease diagnostics and vaccines [27][28][29][30][31]. Thus, proteomic approaches may help to identify such proteins with crucial roles in mediating parasite capacity to modulate the host immune response. Those strategies may enable us to detect and select promising vaccine and diagnostic targets against toxoplasmosis [32][33][34]. Therefore, the aim of this study is bringing together the main functionality relevant proteins from Toxoplasma parasites coming from proteomic approaches most likely to be useful in improving disease management and to critically propose innovative directions to finally develop promising vaccines and diagnostic tools. Accordingly, this work also covers the possible vaccine and diagnostics properties of such important proteins.

References

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  14. Chen, K.; Wang, J.-L.; Huang, S.-Y.; Yang, W.-B.; Zhu, W.-N.; Zhu, X.-Q. Immune responses and protection after DNA vaccination against Toxoplasma gondii calcium-dependent protein kinase 2 (TgCDPK2). Parasite 2017, 24, 41.
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  16. Wang, J.-L.; Li, T.-T.; Elsheikha, H.M.; Chen, K.; Cong, W.; Yang, W.-B.; Bai, M.-J.; Huang, S.-Y.; Zhu, X.-Q. Live Attenuated Pru: Δ cdpk2 Strain of Toxoplasma gondii Protects Against Acute, Chronic, and Congenital Toxoplasmosis. J. Infect. Dis. 2018, 218, 768–777.
  17. Zhang, N.-Z.; Gao, Q.; Wang, M.; Elsheikha, H.M.; Wang, B.; Wang, J.-L.; Zhang, F.-K.; Hu, L.-Y.; Zhu, X.-Q. Immunization with a DNA vaccine cocktail encoding TgPF, TgROP16, TgROP18, TgMIC6, and TgCDPK3 genes protects mice against chronic toxoplasmosis. Front. Immunol. 2018, 9, 1505.
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  22. Wang, Z.-X.; Zhou, C.-X.; Elsheikha, H.M.; He, S.; Zhou, D.-H.; Zhu, X.-Q. Proteomic differences between developmental stages of Toxoplasma gondii revealed by iTRAQ-based quantitative proteomics. Front. Microbiol. 2017, 8, 985.
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Subjects: Parasitology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Sajad Rashidi
,
Javier Sánchez-Montejo
,
Reza Mansouri
,
Mohammad Ali-Hassanzadeh
,
Amir Savardashtaki
,
Mohammad Saleh Bahreini
,
Mohammadreza Karimazar
,
Raúl Manzano-Román
,
Paul Nguewa
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Revisions: 2 times (View History)
Update Date: 21 Jul 2022
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