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Engineering and functional evaluation of neutralizing antibody fragments against congenital toxoplasmosis

Abstract : 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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https://hal.inrae.fr/hal-03186466
Contributor : Nathalie Katy Chanteloup <>
Submitted on : Wednesday, March 31, 2021 - 10:27:13 AM
Last modification on : Tuesday, June 8, 2021 - 3:53:53 PM

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Anne Di Tommaso, Matthieu Juste, Zineb Lakhrif, Marie-Nöelle Mévélec, Coraline Borowczyk, et al.. Engineering and functional evaluation of neutralizing antibody fragments against congenital toxoplasmosis. Journal of Infectious Diseases, Oxford University Press (OUP), In press, ⟨10.1093/infdis/jiab141⟩. ⟨hal-03186466⟩

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