Exploring the Application of Gamma Radiation-Attenuated <i>Toxoplasma gondii</i> Tachyzoites: A Promising Vaccine Candidate Against Toxoplasmosis

Abstract

Background: Toxoplasma gondii is a protozoan parasite with a global distribution. Despite the medical importance of the associated diseases, current therapeutic agents and vaccines are not effective for disease control. Research to find an effective vaccine is ongoing. Attenuated vaccines, particularly those developed through radiation, are promising due to their proper immunogenicity. Objectives: The current study aimed to investigate gamma radiation-attenuated tachyzoites of the T. gondii RH strain as a potential vaccine. Methods: Tachyzoites of the RH strain of T. gondii were exposed to gamma rays at doses of 50, 100, and 200 Gy. Tachyzoite viability was assessed using flow cytometry, and infectivity was assessed in HeLa cell cultures. An in vivo study was conducted by injecting the irradiated tachyzoites into BALB/c mice. Disease progression in inoculated mice was compared to a control group by challenging them with intact tachyzoites of the RH strain. Serum levels of interleukins 2 and 10, and interferon-gamma were measured before and after the vaccine challenge. Results: Flow cytometry showed significant mortality rates in tachyzoites exposed to gamma rays, with 35.28%, 58.31%, and 89.28% mortality at 50, 100, and 200 Gy, respectively. In HeLa cell cultures, gamma ray exposure significantly reduced tachyzoite load compared to controls (P < 0.05). In vivo, mice infected with 50 Gy irradiated tachyzoites showed complete mortality within 14 days, while the 100 Gy group had partial mortality (4 out of 20 died), and the 200 Gy group had full survival. Control mice infected with intact tachyzoites died within 8 days (average survival: 6.8 ± 0.44 days). ELISA results indicated significant increases in cytokine levels (IL-2, IL-10, IFN-γ) in mice treated with 100 Gy and 200 Gy irradiated tachyzoites post-vaccine challenge (P < 0.05). Survival rate monitoring post-vaccine challenge revealed higher survival rates in the 100 Gy and 200 Gy groups compared to controls. Conclusions: The findings of the current study provide significant insights into the potential use of gamma radiation to reduce the pathogenicity of T. gondii and enhance the immune response in infected hosts. Further research is needed to explore their full potential and safety in human populations.