Researchers pull an IgM with ultrapotent neutralization from a pregnant Zika virus patient


Pregnancy-related ZIKV infections increase the danger of vertical transmission from mother to fetus. Up to 14% of newborns are then at risk for congenital neurodevelopmental deficits.

ZIKV infection causes a humoral immune response, similar to other flavivirus infections, that is characterized by enduring IgM serum antibodies. Previous research has demonstrated the importance of fetal IgM monoclonal antibodies (mAbs) in the development of protective immunity against ZIKV. These ZIKV-specific IgM mAbs haven’t been characterized by studies, though.

In the present study, researchers isolated a pentameric ZIKV-specific IgM (DH1017.IgM) from an infected pregnant female to characterize it and develop an understanding of the mechanisms of action of the IgM isotype against ZIKV.

They used blood plasma samples from a cohort of pregnant women with serologically confirmed ZIKV infection from the 2015–2016 ZIKV outbreak that hit Brazil. Serological investigations confirmed that most of these women also had prior exposure to Dengue virus (DENV), termed secondary ZIKV.

Another intriguing observation was that a class of potent IgM mAbs recognize and bind to a quarternary epitope on ZIKV, different from previously identified potent ZIKV-specific mAbs. Most likely, the multimeric structure of the IgM isotype facilitates this binding at high orders of valency.

Narrow scanning micrographs (NSEM) showed that five E dimers in domain II of ZIKV are concurrently bound through an IgM-specific antigen recognition multivalent mode, demonstrating a functional advantage of DH1017.IgM compared to IgG isotype.

NSEM micrographs of a ZIKV also showed virion aggregation in the presence of DH1017. IgM is a potent viral neutralization mode. A five times more dosage of DH1017. IgG achieved a biological effect comparable to DH1017.

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