PLK: Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis

Toxoplasmosis is a zoonotic parasitic disease caused by the obligate intracellular protozoa Toxoplasma gondii, which threatens a range of warm-blooded mammals including humans. To date, it remains a challenge to find safe and effective drug treatment or vaccine against toxoplasmosis. In this study, our results found that the development of a mutant strain based on gene disruption of dense granule protein 9 (gra9) in type II PLK strain decreased parasite replication in vivo, severely attenuated virulence in mice, and significantly reduced the formation of cysts in animals. Hence, we developed an immunization scheme to evaluate the protective immunity of the attenuated strain of Delta gra9 in type II PLK parasite as a live attenuated vaccine against toxoplasmosis in the mouse model. Delta gra9 vaccination-induced full immune responses characterized by significantly high levels of pro-inflammatory cytokine interferon gamma (IFN-gamma) and interleukin-12 (IL-12), maintained the high T gondii-specific immunoglobulin G (IgG) level, and mixed high IgG1/19G2a levels. Their levels provided the complete protective immunity which is a combination of cellular and humoral immunity in mouse models against further infections of lethal doses of type I RH, type II PLK wild-type tachyzoites, or type II PLK cysts. Results showed that Delta gra9 vaccination proved its immunogenicity and potency conferring 100% protection against acute and chronic T gondii challenges. Together, Delta gra9 vaccination provided safe and efficient immune protection against challenging parasites, suggesting that PLK: Delta gra9 is a potentially promising live attenuated vaccine candidate.

Automated summary

The mutant strain based on gene disruption of dense granule protein 9 (gra9) reduced parasite replication, attenuated virulence in mice, and decreased cyst formation. Delta gra9 vaccination induced full immune responses with high levels of pro-inflammatory cytokines, maintaining T gondii-specific antibody levels, and providing complete protective immunity in mouse models. The vaccine proved to be immunogenic and potent, conferring 100% protection against acute and chronic T gondii challenges.