TY - JOUR
T1 - A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus
AU - Magnani, Diogo M.
AU - Silveira, Cassia G.T.
AU - Rosen, Brandon C.
AU - Ricciardi, Michael J.
AU - Pedreño-Lopez, Núria
AU - Gutman, Martin J.
AU - Bailey, Varian K.
AU - Maxwell, Helen S.
AU - Domingues, Aline
AU - Gonzalez-Nieto, Lucas
AU - Avelino-Silva, Vivian I.
AU - Trindade, Mateus
AU - Nogueira, Juliana
AU - Oliveira, Consuelo S.
AU - Maestri, Alvino
AU - Felix, Alvina Clara
AU - Levi, José Eduardo
AU - Nogueira, Mauricio L.
AU - Martins, Mauricio A.
AU - Martinez-Navio, José M.
AU - Fuchs, Sebastian P.
AU - Whitehead, Stephen S.
AU - Burton, Dennis R.
AU - Desrosiers, Ronald C.
AU - Kallas, Esper G.
AU - Watkins, David I.
N1 - Funding Information:
This work was supported by the NIH grant 4P01AI094420-05, the Wallace H. Coulter Center for Translational Research at the University of Miami [http://www.miami.edu/index.php/u_innovation/about_us/whcc/], and the Miami Clinical and Translational Science Institute (CTSI) [http://miamictsi.org].The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the patients for their volunteer donations. We also thank the laboratory and clinical personnel responsible for collecting the plasma samples used in this study.
Publisher Copyright:
© 2017, Public Library of Science. All rights reserved.
PY - 2017/6/12
Y1 - 2017/6/12
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pntd.0005655
DO - 10.1371/journal.pntd.0005655
M3 - Article
C2 - 28604797
AN - SCOPUS:85021339566
VL - 11
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
SN - 1935-2727
IS - 6
M1 - e0005655
ER -