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There are currently no licensed vaccines for Zika virus (ZIKV), which can be congenitally transmitted, potentially leading to microcephaly and neurodevelopmental deficits in newborns. Neutralizing antibodies (nAbs) are a critical component of protective immune responses against ZIKV, with studies primarily focused on identifying neutralizing IgG antibodies. However, infections are also characterized by prolonged ZIKV-specific IgM responses. Here, Singh et al. analysed plasma samples from a previously described cohort of pregnant women from the 2015–2016 ZIKV outbreak in Brazil, and showed that IgM contributes to ZIKV neutralization primarily within the first three months of infection. Probing the B cell compartment of the infected mothers identified B cells producing ZIKV-neutralizing IgM, which were used to establish ZIKV-binding B lymphoblastoid cell lines (B-LCL). One of these B-LCLs produced a pentameric IgM monoclonal antibody, termed DH1017.IgM, which potently and specifically neutralized ZIKV. In mice, DH1017.IgM conferred protection from lethal challenge and controlled viremia more efficiently than the monomeric IgG. Structural studies identified modes of antigen recognition not available to IgG.