A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques

两种人类单克隆抗体的组合可限制寨卡病毒对恒河猴胎儿造成的损害

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作者:Koen K A Van Rompay, Lark L Coffey, Tania Kapoor, Anna Gazumyan, Rebekah I Keesler, Andrea Jurado, Avery Peace, Marianna Agudelo, Jennifer Watanabe, Jodie Usachenko, Anil Singapuri, Ramya Immareddy, Amir Ardeshir, Jackson B Stuart, Stylianos Bournazos, Jeffrey V Ravetch, Paul J Balderes, Ivo C Loren

Abstract

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement (ADE) in vitro and extend their half-lives. Here we report on prophylactic coadministration of the Fc-modified antibodies to pregnant rhesus macaques challenged three times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission, protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.

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