Engineering and Functional Evaluation of Neutralizing Antibody Fragments Against Congenital Toxoplasmosis.

Autor: Tommaso, Anne di, Juste, Matthieu O, Lakhrif, Zineb, Mévélec, Marie-Noëlle, Borowczyk, Coraline, Hammeni, Pierre, Désoubeaux, Guillaume, Langendonck, Nathalie Van, Debierre-Grockiego, Françoise, Aubrey, Nicolas, Dimier-Poisson, Isabelle, di Tommaso, Anne, Van Langendonck, Nathalie
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Zdroj: Journal of Infectious Diseases; 8/15/2021, Vol. 224 Issue 4, p705-714, 10p
Abstrakt: Maternal-fetal transmission of Toxoplasma gondii tachyzoites acquired during pregnancy has potentially dramatic consequences for the fetus. Current reference-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-single-chain fragment variable (scFv) and scFv fused with mouse immunoglobulin G2a crystallizable fragment (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 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index