Live-attenuated Toxoplasma gondii PruΔpp2a-c mutant elicits protective immunity against toxoplasmosis in mice and cats.

Abstract

Toxoplasma gondii is a zoonotic protozoan pathogen capable of infecting humans and nearly all warm-blooded animals, and causing substantial economic losses to the livestock industry. Developing an effective vaccine against T. gondii remains an urgent priority for controlling the spread of this zoonotic parasite. In this study, we evaluated the protective efficacy of a live-attenuated T. gondii Pru&#x394;pp2a-c mutant in both mice and cats. Immunization with Pru&#x394;pp2a-c elicited strong cellular (IL-2, IL-4, IL-10, IL-12, and IFN-&#x3b3;) and humoral (IgG, IgG1, and IgG2a) immune responses in mice, conferring protection against lethal challenge with various T. gondii strains, including highly virulent Type I (RH), mildly virulent ToxoDB#9 (PYS), and less virulent Type II (Pru) strains. While partial protection was observed against virulent strains, almost complete immune protection was achieved against both acute and chronic infections by the less virulent Pru strain, along with a significant reduction in brain cyst burden (P&#xa0;<&#xa0;0.001). Notably, vaccination of cats with Pru&#x394;pp2a-c induced high antibody titers and led to a 94.5&#xa0;% reduction in fecal oocyst shedding (P&#xa0;<&#xa0;0.001) following homologous challenge, thereby significantly decreasing the potential for environmental transmission. These findings demonstrate that Pru&#x394;pp2a-c provides strong cross-protection against various T. gondii strains and substantially limits oocyst shedding. The dual efficacy observed in both intermediate and definitive hosts highlights Pru&#x394;pp2a-c as a promising live-attenuated vaccine candidate for preventing transmission of T. gondii by cats.