Abstract
Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70). Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant. Indeed, ex vivo experiments showed that peritoneal macrophages pre-stimulated with rTgHSP70 presented increased NO production and enhanced parasite killing, and the protein was able to directly stimulate B cells toward antibody producing profile. In addition, rTgHSP70 immunization leads to high specific antibody titters systemically and a mixed IgG1/IgG2a response, with predominance of IgG1 production. Nonetheless, it was observed that the pretreatment of the parasite with rTgHSP70 immune sera was not able to control T. gondii internalization and replication by NIH fibroblast neither peritoneal murine macrophages, nor anti-rTgHSP70 antibodies were able to kill T. gondii by complement-mediated lysis, suggesting that these mechanisms are not crucial to resistance. Interestingly, when in combination with Alum, rTgHSP70 immunization was able to reduce inflammation in the brain of infected mice and in parallel anti-rTgHSP70 immune complexes in the serum. In conclusion, immunization with rTgHSP70 induces massive amounts of iNOS expression and reduced brain parasitism, suggesting that iNOS expression and consequently NO production in the brain is a protective mechanism induced by TgHSP70 immunization, therefore rTgHSP70 can be a good candidate for vaccine development against toxoplasmosis.
Highlights
Because there is no current effective vaccine for humans, prevention of toxoplasmosis transmission seem to be the best method for controlling the disease (Verma and Khanna, 2013)
It was observed that mice inoculated with phosphate-buffered saline (PBS), Alum, or rTgHSP70 alone showed inflammatory changes in the brain characterized by infiltration of inflammatory cells in the meninges, perivascular cuffs, glial nodules, and inflammatory cells throughout the parenchyma
Immunization with 100 μg rTgHSP70 prolonged the survival rate of mice challenged with RH strain, and this effect was more effective when rTgHSP70 was used with the adjuvant ginseng stem-and-leaf saponins (Zhuo et al, 2016)
Summary
Because there is no current effective vaccine for humans, prevention of toxoplasmosis transmission seem to be the best method for controlling the disease (Verma and Khanna, 2013). The only commercially available vaccine used to prevent toxoplasmosis is derived from live attenuated T. gondii (non-cyst-forming S48strain), Toxovax, and it is used in sheep and goats to avoid abortion (Buxton and Innes, 1995), the safety of this vaccine for humans and food-producing animals is uncertain. The mechanisms associated with the protection still remain poorly understood
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
