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

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. Lorenz, Shannon R. Esswein, Jennifer R. KeeffePamela J. Bjorkman, Qiao Wang, Charles M. Rice, Margaret R. MacDonald, Michel C. Nussenzweig, Davide F. Robbiani

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)7981-7989
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number14
DOIs
StatePublished - Apr 7 2020

Keywords

  • Antibody-Dependent enhancement
  • Congenital Zika syndrome
  • Fc domain modifications
  • Macaque pregnancy model
  • Zika virus

ASJC Scopus subject areas

  • General

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  • Cite this

    van Rompay, K. K. A., Coffey, L. L., Kapoor, T., Gazumyan, A., Keesler, R. I., Jurado, A., Peace, A., Agudelo, M., Watanabe, J., Usachenko, J., Singapuri, A., Immareddy, R., Ardeshir, A., Stuart, J. B., Bournazos, S., Ravetch, J. V., Balderes, P. J., Lorenz, I. C., Esswein, S. R., ... Robbiani, D. F. (2020). A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques. Proceedings of the National Academy of Sciences of the United States of America, 117(14), 7981-7989. https://doi.org/10.1073/pnas.2000414117