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

Autor:	Van Rompay KKA; California National Primate Research Center, University of California, Davis, CA 95616; kkvanrompay@ucdavis.edu nussen@rockefeller.edu drobbiani@rockefeller.edu.; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616., Coffey LL; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616., Kapoor T; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065., Gazumyan A; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065., Keesler RI; California National Primate Research Center, University of California, Davis, CA 95616., Jurado A; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065., Peace A; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065., Agudelo M; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065., Watanabe J; California National Primate Research Center, University of California, Davis, CA 95616., Usachenko J; California National Primate Research Center, University of California, Davis, CA 95616., Singapuri A; California National Primate Research Center, University of California, Davis, CA 95616., Immareddy R; California National Primate Research Center, University of California, Davis, CA 95616., Ardeshir A; California National Primate Research Center, University of California, Davis, CA 95616., Stuart JB; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616., Bournazos S; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065., Ravetch JV; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065., Balderes PJ; Tri-Institutional Therapeutics Discovery Institute, New York, NY 10065., Lorenz IC; Tri-Institutional Therapeutics Discovery Institute, New York, NY 10065., Esswein SR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125., Keeffe JR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125., Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125., Wang Q; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.; Key Laboratory of Medical Molecular Virology of Ministry of Education/National Health Commission/Chinese Academy of Medical Sciences, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, 200032 Shanghai, China., Rice CM; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065., MacDonald MR; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065., Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065; kkvanrompay@ucdavis.edu nussen@rockefeller.edu drobbiani@rockefeller.edu.; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065., Robbiani DF; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065; kkvanrompay@ucdavis.edu nussen@rockefeller.edu drobbiani@rockefeller.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Apr 07; Vol. 117 (14), pp. 7981-7989. Date of Electronic Publication: 2020 Mar 24.
DOI:	10.1073/pnas.2000414117
Abstrakt:	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. Competing Interests: Competing interest statement: The Rockefeller University, D.F.R., and M.C.N. have filed a patent application for antibodies Z004 and Z021. (Copyright © 2020 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu