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.