Protective efficacy of two novel DNA vaccines expressing Toxoplasma gondii rhomboid 4 and rhomboid 5 proteins against acute and chronic toxoplasmosis in mice

Abstract

Objectives: To evaluate the protective efficacy of two novel DNA vaccines expressing Toxoplasma gondii rhomboid 4 (ROM4) and rhomboid 5 (ROM5) proteins against acute and chronic toxoplasmosis. Methods: DNA vaccines (pVAX-TgROM5 and pVAX-TgROM4) were constructed and their immunogenicity evaluated in Kunming mice. Results: Mice vaccinated with pVAX-TgROM5 or pVAX-TgROM4 elicited strong Th1-type humoral and cellular responses, with higher level of IgG antibody titers (the predominance of IgG2a production), and increased levels of CD4⁺ and CD8⁺ T cells and cytokines IFN-γ, IL-2, IL-12 (p70) and IL-23. Mice vaccinated with pVAX-TgROM5 (11 days) showed a significantly longer survival time compared with controls (8 days) (p < 0.05) after lethal challenge. Brain cyst numbers of mice vaccinated with pVAX-TgROM5 and pVAX-TgROM4 reduced significantly (p < 0.05) (72.04 and 44.08%, respectively) compared with control groups after chronic challenge.Conclusion: The pVAX-TgROM5 showed a better protective efficacy against acute and chronic toxoplasmosis compared to pVAX-TgROM4.

Keywords:

• DNA vaccine
• immune response
• protective immunity
• ROM4
• ROM5
• Toxoplasma gondii

Financial & competing interest’s disclosure

This work was supported by the Natural Science Foundation of Gansu Province (Grant No. 1308RJYA092), the National Natural Science Foundation of China (Grant Nos. 31172316, 31230073) and the Science Fund for Creative Research Groups of Gansu Province (Grant No. 1210RJIA006). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Toxoplasmosis is a major public health problem worldwide, and many efforts have focused on the development of vaccines against the disease.

• Vaccination with Toxoplasma gondii ROM5 or ROM4 DNA vaccine induced strong humoral and cellular responses.

• Higher levels of IFN-γ, IL-2, IL-12, IL-23 and IL-4 were observed after DNA vaccination, and immunization with pVAX-TgROM5 associated with a Th1-type response.

• Vaccination with pVAX-TgROM5 resulted in a significantly prolonged survival time and increased survival rate (3/15) of immunized mice.

• Significant reduction in brain cyst number was observed after vaccination with both DNA plasmids.

• Both TgROM4 and TgROM5 are potential vaccine candidates against acute and chronic toxoplasmosis, and a better protective efficacy was detected in vaccination with pVAX-TgROM5.

Notes