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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 |
Appears in Collections: | Staff Publications Elements |
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