Engineering and functional evaluation of neutralizing antibody fragments against congenital toxoplasmosis

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Di Tommaso, Anne | Juste, Matthieu | Lakhrif, Zineb | Mévélec, Marie-Nöelle | Borowczyk, Coraline | Hammeni, Pierre | Desoubeaux, Guillaume | van Langendonck, Nathalie | Debierre-Grockiego, Françoise | Aubrey, Nicolas | Dimier-Poisson, Isabelle

Edité par CCSD ; Oxford University Press -

International audience. Maternal-fetal transmission of Toxoplasma gondii tachyzoites acquired during pregnancy has potentially dramatic consequences for the fetus. Current gold-standard treatments are not specific to the parasite and can induce severe side effects. In order to provide treatments with a higher specificity against toxoplasmosis, we developed antibody fragments - scFv, scFv-Fc - directed against the major surface protein SAG1. After validating their capacity to inhibit T. gondii proliferation in vitro, the antibody fragments' biological activity was assessed in vivo using a congenital toxoplasmosis mouse model. Dams were treated by systemic administration of antibody fragments and with prevention of maternal-fetal transmission being used as the parameter of efficacy. We observed that both antibody fragments prevented T. gondii dissemination and protected neonates, with the scFv-Fc format having a better efficacy. These data provide a proof-of-concept for the use of antibody fragments as effective and specific treatment against congenital toxoplasmosis and provide promising leads.

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