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A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization.

Publication ,  Journal Article
Singh, T; Hwang, K-K; Miller, AS; Jones, RL; Lopez, CA; Dulson, SJ; Giuberti, C; Gladden, MA; Miller, I; Webster, HS; Eudailey, JA; Luo, K ...
Published in: Cell
December 8, 2022

Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM contributes to ZIKV immunity in pregnancy, mediating neutralization up to 3 months post-symptoms. From a ZIKV-infected pregnant woman, we isolated a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets an envelope dimer epitope within domain II. The epitope arrangement on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not available to IgG. DH1017.IgM protected mice against viremia upon lethal ZIKV challenge more efficiently than when expressed as an IgG. Our findings identify a role for antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunotherapeutic, particularly during pregnancy.

Duke Scholars

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

December 8, 2022

Volume

185

Issue

25

Start / End Page

4826 / 4840.e17

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Pregnancy
  • Neutralization Tests
  • Mice
  • Immunoglobulin M
  • Female
  • Epitopes
  • Developmental Biology
  • Antibodies, Viral
 

Citation

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Chicago
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Singh, T., Hwang, K.-K., Miller, A. S., Jones, R. L., Lopez, C. A., Dulson, S. J., … Bonsignori, M. (2022). A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. Cell, 185(25), 4826-4840.e17. https://doi.org/10.1016/j.cell.2022.10.023
Singh, Tulika, Kwan-Ki Hwang, Andrew S. Miller, Rebecca L. Jones, Cesar A. Lopez, Sarah J. Dulson, Camila Giuberti, et al. “A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization.Cell 185, no. 25 (December 8, 2022): 4826-4840.e17. https://doi.org/10.1016/j.cell.2022.10.023.
Singh T, Hwang K-K, Miller AS, Jones RL, Lopez CA, Dulson SJ, et al. A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. Cell. 2022 Dec 8;185(25):4826-4840.e17.
Singh, Tulika, et al. “A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization.Cell, vol. 185, no. 25, Dec. 2022, pp. 4826-4840.e17. Pubmed, doi:10.1016/j.cell.2022.10.023.
Singh T, Hwang K-K, Miller AS, Jones RL, Lopez CA, Dulson SJ, Giuberti C, Gladden MA, Miller I, Webster HS, Eudailey JA, Luo K, Von Holle T, Edwards RJ, Valencia S, Burgomaster KE, Zhang S, Mangold JF, Tu JJ, Dennis M, Alam SM, Premkumar L, Dietze R, Pierson TC, Ooi EE, Lazear HM, Kuhn RJ, Permar SR, Bonsignori M. A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. Cell. 2022 Dec 8;185(25):4826-4840.e17.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

December 8, 2022

Volume

185

Issue

25

Start / End Page

4826 / 4840.e17

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Pregnancy
  • Neutralization Tests
  • Mice
  • Immunoglobulin M
  • Female
  • Epitopes
  • Developmental Biology
  • Antibodies, Viral