Gene-edited live-attenuated vaccines against Toxoplasma gondii: recent advances and future frontiers

Toxoplasma gondii is an infectious disease that infects nearly one third of the world's population and endangers the health of immunocompromised people, pregnant women, and livestock. There are no existing drugs able to treat the infection and prevent tissue cysts from developing. Therefore, the creation of a safe vaccine should be considered as a matter of great importance. While many of the vaccines have not proven successful in the past, recently created live-attenuated vaccines (LAVs) using CRISPR-Cas9 gene editing technology were able to outperform the previous ones. The current review aims to highlight the recent progress in genetically engineered LAVs against T. gondii. In particular, the knockout strains affecting metabolic genes (ompdc, uprt, and adsl), virulence genes (rop18), and host-parasite interactions (gra5, gra72, had2a, and cdpk3) will be mentioned. LAVs described above demonstrate high attenuating effects and ability to protect mice by inducing immunity on the basis of specific IgG (IgG2a), IFN-γ, IL-12, and CD4⁺, CD8⁺ T cells. Furthermore, vaccination provides protection from a lethal infection caused by types I, II, and Chinese 1 strains of T. gondii as well as preventing development of tissue cysts in chronic infection. RHΔompdcΔuprt is an example of an LAV that can be used to reduce oocyst shedding in cats and promote the One Health concept. In general terms, genetically engineered LAVs can effectively deal with toxoplasmosis infection with better attenuation immunogenicity balance than other vaccines. Nonetheless, several problems need consideration.