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

Authors :
Koen K. A. Van Rompay
Andrea Jurado
Charles M. Rice
Lark L. Coffey
Ivo C. Lorenz
Ramya Immareddy
Jennifer Watanabe
Jeffrey V. Ravetch
Jennifer R. Keeffe
Qiao Wang
Anna Gazumyan
Amir Ardeshir
Michel C. Nussenzweig
Rebekah I. Keesler
Marianna Agudelo
Jackson B. Stuart
Margaret R. MacDonald
Avery Peace
Shannon R. Esswein
Pamela J. Bjorkman
Stylianos Bournazos
Jodie Usachenko
Davide F. Robbiani
Anil Singapuri
Paul J. Balderes
Tania Kapoor
Source :
Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 14, Proceedings of the National Academy of Sciences of the United States of America
Publication Year :
2020
Publisher :
eScholarship, University of California, 2020.

Abstract

Significance Zika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease-enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.<br />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.

Details

Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 14, Proceedings of the National Academy of Sciences of the United States of America
Accession number :
edsair.doi.dedup.....8532a9277cda828e4e1165743df99d18