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J Exp Med. 2019 Oct 7;216(10):2302-2315. doi: 10.1084/jem.20191061. Epub 2019 Aug 14.

Risk of Zika microcephaly correlates with features of maternal antibodies.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY drobbiani@rockefeller.edu.
2
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
3
Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
4
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT.
5
Faculdade de Medicina and Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
6
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
7
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia, Brazil.
8
Hospital Geral Roberto Santos, Secretária da Saúde do Estado da Bahia, Salvador, Brazil.
9
Universidade Federal de São Paulo, São Paulo, Brazil.
10
Instituto Evandro Chagas, Ministério da Saúde Ananindeua, Pará, Brazil.
11
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY.
12
Hospital Santo Amaro, Salvador, Bahia, Brazil.
13
Hospital Aliança, Salvador, Bahia, Brazil.
14
California National Primate Research Center, University of California, Davis, Davis, CA.
15
Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA.
16
Washington National Primate Research Center, Seattle, WA.
17
Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA.
18
Department of Immunology, University of Washington, Seattle, WA.
19
Department of Global Health, University of Washington, Seattle, WA.
20
Department of Pediatrics, University of Washington, Seattle, WA.
21
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA.
22
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA.
23
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
24
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI.
25
Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR.
26
Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR.
27
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR.
28
Pathology Services Unit, Division of Comparative Medicine, Oregon National Primate Research Center, Beaverton, OR.
29
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR.
30
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY nussen@rockefeller.edu.
31
Howard Hughes Medical Institute, The Rockefeller University, New York, NY.
#
Contributed equally

Abstract

Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015-2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

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