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Aim:Development of protein vaccine to prevent congenital infection is a major public health priority. Our goal is the design of mucosal synthetic pathogen inducing protective immune responses against congenital toxoplasmosis. Materials & methods:Mice were immunized intranasally, establishing pregnancy and challenging orally. Placental immune response, congenital infection, pup growth, parasitic load rates were studied. Results:Pups born to vaccinated infected dams had significantly fewer brain cysts, no intraocular inflammation and normal growth. Protection was associated with a placental cellular Th1 response downregulated by IL-6 and correlated with persistence of vaccine for few hours in the nose before being totally eliminated. Conclusion:Our vaccine conferred high protection against congenital toxoplasmosis. These results provide support for future studies of other congenital vaccine.