Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.cell.2022.10.023
Title: A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization
Authors: Singh, Tulika
Hwang, Kwan-Ki
Miller, Andrew S
Jones, Rebecca L
Lopez, Cesar A
Dulson, Sarah J
Giuberti, Camila
Gladden, Morgan A
Miller, Itzayana
Webster, Helen S
Eudailey, Joshua A
Luo, Kan
Von Holle, Tarra
Edwards, Robert J
Valencia, Sarah
Burgomaster, Katherine E
Zhang, Summer 
Mangold, Jesse F
Tu, Joshua J
Dennis, Maria
Alam, S Munir
Premkumar, Lakshmanane
Dietze, Reynaldo
Pierson, Theodore C
Ooi, Eng Eong 
Lazear, Helen M
Kuhn, Richard J
Permar, Sallie R
Bonsignori, Mattia
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
IMMUNOGLOBULIN-M ANTIBODIES
DENGUE
PROTECTION
VACCINE
MICROSCOPY
CHALLENGE
PERSISTENCE
INFECTION
EFFICACY
BROAD
Issue Date: 8-Dec-2022
Publisher: CELL PRESS
Citation: Singh, Tulika, Hwang, Kwan-Ki, Miller, Andrew S, Jones, Rebecca L, Lopez, Cesar A, Dulson, Sarah J, Giuberti, Camila, Gladden, Morgan A, Miller, Itzayana, Webster, Helen S, Eudailey, Joshua A, Luo, Kan, Von Holle, Tarra, Edwards, Robert J, Valencia, Sarah, Burgomaster, Katherine E, Zhang, Summer, Mangold, Jesse F, Tu, Joshua J, Dennis, Maria, Alam, S Munir, Premkumar, Lakshmanane, Dietze, Reynaldo, Pierson, Theodore C, Ooi, Eng Eong, Lazear, Helen M, Kuhn, Richard J, Permar, Sallie R, Bonsignori, Mattia (2022-12-08). A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. CELL 185 (25) : 4826-+. ScholarBank@NUS Repository. https://doi.org/10.1016/j.cell.2022.10.023
Abstract: 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.
Source Title: CELL
URI: https://scholarbank.nus.edu.sg/handle/10635/241883
ISSN: 0092-8674
1097-4172
DOI: 10.1016/j.cell.2022.10.023
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