1. A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques
- Author
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Van Rompay, Koen KA, Coffey, Lark L, Kapoor, Tania, Gazumyan, Anna, Keesler, Rebekah I, Jurado, Andrea, Peace, Avery, Agudelo, Marianna, Watanabe, Jennifer, Usachenko, Jodie, Singapuri, Anil, Immareddy, Ramya, Ardeshir, Amir, Stuart, Jackson B, Bournazos, Stylianos, Ravetch, Jeffrey V, Balderes, Paul J, Lorenz, Ivo C, Esswein, Shannon R, Keeffe, Jennifer R, Bjorkman, Pamela J, Wang, Qiao, Rice, Charles M, MacDonald, Margaret R, Nussenzweig, Michel C, and Robbiani, Davide F
- Subjects
Medical Microbiology ,Reproductive Medicine ,Biomedical and Clinical Sciences ,Immunology ,Vector-Borne Diseases ,Women's Health ,Perinatal Period - Conditions Originating in Perinatal Period ,Biodefense ,Maternal Health ,Prevention ,Emerging Infectious Diseases ,Pregnancy ,Vaccine Related ,Immunization ,Rare Diseases ,Infectious Diseases ,Pediatric ,5.1 Pharmaceuticals ,Reproductive health and childbirth ,Infection ,Good Health and Well Being ,Animals ,Animals ,Newborn ,Antibodies ,Monoclonal ,Antibodies ,Neutralizing ,Disease Models ,Animal ,Drug Therapy ,Combination ,Female ,Fetus ,HEK293 Cells ,Humans ,Immunoglobulin Fc Fragments ,Immunoglobulin G ,Infectious Disease Transmission ,Vertical ,Pregnancy Complications ,Infectious ,Protein Engineering ,RNA ,Viral ,Recombinant Proteins ,Zika Virus ,Zika Virus Infection ,Fc domain modifications ,Zika virus ,macaque pregnancy model ,antibody-dependent enhancement ,congenital Zika syndrome - 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.
- Published
- 2020