The Specificity of the Persistent IgM Neutralizing Antibody Response in Zika Viral Infections Among Individuals with Prior Dengue Virus Exposure
Dengue viruses (DENV) and Zika virus (ZIKV) are related mosquito-borne flaviviruses with similar disease manifestations, vector ecology and geographic range. The ability to differentiate these viruses serologically is vital due to the teratogenic nature of ZIKV and the potential confounding of pre-existing cross-reactive anti-DENV antibodies. Here we illustrate the kinetics of the IgM neutralizing antibody (NAb) response using longitudinal samples ranging from acute ZIKV infection to late convalescence from individuals with evidence of prior DENV infection. By serially depleting antibody isotypes prior to neutralization assay, we determined that IgM contributes predominantly to ZIKV neutralization, and it is less cross-reactive than the IgG NAb. The IgM NAb peaked around 14 days (95% CI: 13-15) with a median duration of 257 days (95% CI: 133-427). These results demonstrate the persistence of IgM NAb after ZIKV infections and imply its potential role in diagnosis, vaccine evaluation, serosurveillance, and research of flaviviral-host interactions.