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Significance The CDC estimates that every hour, a child is born in the United States with permanent neurologic disability resulting from human cytomegalovirus (HCMV) infection—more than is caused by Down syndrome, fetal alcohol syndrome, and neural tube defects combined. A maternal vaccine to block transmission of HCMV to the developing fetus is a necessary intervention to prevent these adverse outcomes. The gB/MF59 vaccine is the most successful tested clinically to date, achieving 50% reduction in HCMV acquisition. This manuscript establishes the function and epitope specificity of the humoral response stimulated by this vaccine that may explain the partial vaccine efficacy. Understanding the mechanism of gB/MF59-elicited protective immune responses will guide rational design and evaluation of the next generation of HCMV vaccines.

HCMV glycoprotein B subunit vaccine efficacy mediated by nonneutralizing antibody effector functions