Nanoparticle-Based Vaccines Against Toxoplasma gondii: Immunological Rationale, Platform Strategies, and Translational Challenges.

Toxoplasma gondii is a widely distributed zoonotic pathogen with detrimental impacts on both human health and livestock production. No vaccine is available for humans, and the only licensed veterinary vaccine, Toxovax, has limitations related to safety, stability, and large-scale production. In this review, we analyze nanoparticle platforms, including PLGA, chitosan, lipid nanoparticles, calcium phosphate nanoparticles, virus-like particles, and porous delivery systems, in relation to antigen uptake and MHC-I/MHC-II presentation, Th1-polarized cellular immunity, and mucosal vaccination. We also consider how antigen selection, carrier properties, route of administration, and host species influence immune responses and protection. Available studies show that different antigens may perform differently within the same platform and that the same antigen may induce different outcomes when delivered by different carriers. From a One Health perspective, feline vaccination may reduce environmental oocyst contamination, whereas livestock vaccination may reduce tissue cysts and food-borne transmission. Although parenteral mRNA-LNP vaccines have reduced chronic-stage parasite burdens in mice, direct evidence that they induce intestinal mucosal immunity remains limited. Key translational issues include validation in nonrodent hosts, chronic-stage and mucosal endpoints, manufacturing scalability, and regulatory approval. Nanoparticle vaccines remain promising, but their successful development will require closer matching of antigen, platform, administration route, and target host.