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タイトル | A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. |
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ジャーナル・号・ページ | Cell, Vol. 185, Issue 25, Page 4826-4840.e17, Year 2022 |
掲載日 | 2022年12月8日 |
著者 | Tulika Singh / Kwan-Ki Hwang / Andrew S Miller / Rebecca L Jones / Cesar A Lopez / Sarah J Dulson / Camila Giuberti / Morgan A Gladden / Itzayana Miller / Helen S Webster / Joshua A Eudailey / Kan Luo / Tarra Von Holle / Robert J Edwards / Sarah Valencia / Katherine E Burgomaster / Summer Zhang / Jesse F Mangold / Joshua J Tu / Maria Dennis / S Munir Alam / Lakshmanane Premkumar / Reynaldo Dietze / Theodore C Pierson / Eng Eong Ooi / Helen M Lazear / Richard J Kuhn / Sallie R Permar / Mattia Bonsignori / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:36402135 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 5.26 Å |
構造データ | EMDB-25606: Zika Virus particle bound with IgM antibody DH1017 Fab fragment |
由来 |
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キーワード | VIRUS / Zika Virus particle / IgM / Fab fragment / Neutralization |