Toxoplasmosis is caused by an intracellular parasite called Toxoplasma gondii (T. gondii). This parasite is common between humans and animals (zoonosis) that are capable to create diseases in all warm-blooded animals and is considered an important pathogen for humans (Hill and Dubey, 2002; Wyrosdick and Schaefer, 2015). T. gondii could be transferred to humans via eating meat containing parasite tissue bradyzoites, drinking contaminated water and milk with the tachyzoites, blood transition (Moghimi et al., 2015), and organ transplantation (Carme et al., 2002). According to several transmission routes, toxoplasmosis is considered as a prevalent infection in most areas of the world, highlighting its medical and veterinary importance (Tenter et al., 2000). The importance of toxoplasmosis is for the immunodeficiency patients such as AIDS and pregnant women who are infected for the first time in pregnancy (Dakshina et al., 2018). Sometimes, toxoplasmosis could led to an eye infection and the next blindness would have happened without treatment. Lymphadenitis is a kind of self-limited disease that is right after a few months. In reaction to this infection, CD4+ and CD8+ T cells as well as B cells with corroboration together could be able to exert long-term protection against infection.

Various vaccine candidates against toxoplasmosis have been tested in animal models using different antigens and adjuvants in the vaccine formulation. However, none of these vaccines have been approved as yet. The most important challenges in the vaccine development is that the inefficacy in eliminating the tissue cysts and also blocking the vertical transmission. Therefore, current strategy in the controlling the infection is based mainly on treatment by therapeutic agents (Wang et al., 2019). Available drugs include primary plus folic acid, sulfadiazine, clindamycin, and cotrimoxazole which are often utilized primarily plus sulfadiazine. However, treatment with these drugs has some side effects such as neutropenia, osteoporosis, and blood toxicity. In addition, sulfadiazine not only is unable to omit infection, but also causes a wide variety of side effects such as hypersensitivity, crystalluria, and hematuria, especially in patients with immunodeficiency which could be caused by disease relapse (Engstrom et al., 1991; Opremcak et al., 1992).

In this respect, the available vaccines lack the ability to induce long-term protection against T. gondii in recent decades. Protein vaccines cause B cell responses to have high performance through neutralizing pathogens by antibodies and are valuable to diagnosis but could not create enough immunity (Denkers et al., 1993; Johnson et al., 2004). Generally, immunological limitations have encountered problems with vaccine development against T. gondii with a variety of antigens (Chu and Quan, 2021). According to observations, research should be continued to find effective drugs with low toxicity and high efficiency. Therefore, herbal therapeutics would be considered as a valuable alternative. Natural products originated from medicinal plants are the key source of expansion of pharmaceutical compounds. Medicine plants are beneficial tools to treat the disease due to lower side effects as compared with chemical drugs (Radmehr et al., 2020). In this respect, curcumin as hydrophobic, poly-phenolic, and non-toxic compounds has a wide spectrum of anti-microbial, anti-oxidant, anti-inflammatory, and anticancer activities (Akbar et al., 2018; Mandroli and Bhat, 2013).

In vivo studies have shown anti-trypanosome and anti-malaria effects in Trypanosoma evanci and Plasmodium falciparum, respectively. The immunomodulatory effects of curcumin substance on the immune system are determined (Jagetia and Aggarwal, 2007). Some studies have shown the ability of curcumin to suppress thymocyte proliferation and inhibit spleen and cytotoxicity lymphocytes as well as cytokines such as IFN-γ and IL-2 (Sikora et al., 1997). Along with this, several studies indicated that curcumin can regulate the NF-kB pathway and decrease IL-2 production. Another study demonstrated that curcumin is capable to suppress the cellular cycle via downregulation of Cyclin D1, Cdk1, and Cdc25c and block the proliferation of polluted cells with HTLV-1. Otherwise, other studies indicated that curcumin could increase T and B-lymphocyte proliferation and IFN-γ cytokine release (Gao et al., 2004; Ranjan et al., 1998).

A recent study has shown that curcumin has immunomodulatory effects and can be used as an adjuvant in the treatment of chronic diseases (Terby et al., 2021). Some studies revealed the role of curcumin in the treatment of some diseases such as toxoplasmosis. It has been shown that curcumin nanoemulsion has a potential formula for the treatment of acute and chronic toxoplasmosis in mice, especially in those with latent bradyzoites in the brain (Azami et al., 2018). The anti-toxoplasma effects of some traditional medicinal plant extracts including Curcuma have long been proven (Al Nasr et al., 2016). In addition, it has been shown that a novel formulation of dendrosomal nano-curcumin has potent anti-tumor properties on the different mouse and human cancer cells, including fibrosarcoma, gastric, colon, glioblastoma, bladder, breast, and hepatocellular carcinoma in vitro and vivo (Dendrosomal nano-curcumin; the novel formulation to improve the anticancer properties of curcumin).

Here, we hypothesized that the formulation of killed T. gondii in nanocurcumin drug may result in an improvement of the vaccine potency and also efficacy. Therefore, killed T. gondii was formulated in nanocurcumin and curcumin drugs, followed by the assessment of cellular and humoral immune parameters. In addition, the vaccine efficacy was evaluated in the murine challenge model.