Engineering and functional evaluation of neutralizing antibody fragments against congenital toxoplasmosis
2021
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 | Infectiologie et Santé Publique (ISP) ; Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Institut des Sciences Moléculaires (ISM) ; Université de Bordeaux (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) | Service ophtalmologie [Tours] ; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) | Service de parasitologie, mycologie, médecine tropicale [CHRU Tours] | Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR) ; Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Région Centre-Val de Loire: appel à projets de recherche d'intérêt régional (APR IR) "AbTox" | ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010)
International audience
Show more [+] Less [-]English. 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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