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J Infect Dis ; 224(4): 705-714, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-33728452

RESUMO

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.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antiprotozoários/imunologia , Engenharia de Proteínas , Anticorpos de Cadeia Única , Toxoplasmose Congênita , Animais , Feminino , Camundongos , Gravidez , Anticorpos de Cadeia Única/imunologia , Toxoplasma/imunologia , Toxoplasmose Congênita/tratamento farmacológico , Toxoplasmose Congênita/prevenção & controle
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