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PLoS Negl Trop Dis. 2017 Jun 12;11(6):e0005655. doi: 10.1371/journal.pntd.0005655. eCollection 2017 Jun.

A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus.

Author information

1
Department of Pathology University of Miami, Miami, FL, United States of America.
2
Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
3
Hospital Sírio-Libanês, São Paulo, SP, Brazil.
4
Neurology Department, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
5
Instituto Adolfo Lutz, São Paulo, SP, Brazil.
6
Instituto Evandro Chagas, Belém, PA, Brazil.
7
Departamento de Moléstias Infecciosas e Parasitárias-(LIM-52), Instituto de Medicina Tropical de São Paulo e Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
8
Laboratório de Pesquisas em Virologia, Departamento de Doenças Dermatológicas, Infecciosas e Parasitárias, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
9
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
10
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States of America.
11
The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States of America.

Abstract

The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut50 ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.

PMID:
28604797
DOI:
10.1371/journal.pntd.0005655
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