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Cell. 2017 May 4;169(4):597-609.e11. doi: 10.1016/j.cell.2017.04.024.

Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Electronic address: drobbiani@rockefeller.edu.
2
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
3
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
4
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia CEP 40296-710, Brazil.
5
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
6
National Institute of Respiratory Diseases, Mexico City CP 14080, Mexico.
7
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia CEP 40296-710, Brazil; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA.
8
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia CEP 40296-710, Brazil; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA; Faculdade de Medicina da Bahia and Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Bahia CEP 40296-710, Brazil.
9
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA.
10
Faculdade de Medicina da Bahia and Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Bahia CEP 40296-710, Brazil.
11
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA. Electronic address: macdonm@rockefeller.edu.
12
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. Electronic address: nussen@rockefeller.edu.

Abstract

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

KEYWORDS:

Zika virus; antibodies; dengue virus; flavivirus; structure; vaccine

PMID:
28475892
PMCID:
PMC5492969
DOI:
10.1016/j.cell.2017.04.024
[Indexed for MEDLINE]
Free PMC Article

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