Blockade of dengue virus transmission from viremic blood to Aedes aegypti mosquitoes using human monoclonal antibodies

Background Dengue is the most prevalent arboviral disease of humans. Virus neutralizing antibodies are likely to be critical for clinical immunity after vaccination or natural infection. A number of human monoclonal antibodies (mAbs) have previously been characterized as able to neutralize the infectivity of dengue virus (DENV) for mammalian cells in cell-culture systems. Methodology/Principle findings We tested the capacity of 12 human mAbs, each of which had previously been shown to neutralize DENV in cell-culture systems, to abrogate the infectiousness of dengue patient viremic blood for mosquitoes. Seven of the twelve mAbs (1F4, 14c10, 2D22, 1L12, 5J7, 747(4)B7, 753(3)C10), almost all of which target quaternary epitopes, inhibited DENV infection of Ae. aegypti. The mAbs 14c10, 747(4)B7 and 753(3)C10 could all inhibit transmission of DENV in low microgram per mL concentrations. An Fc-disabled variant of 14c10 was as potent as its parent mAb. Author summary Dengue is the most prevalent arboviral disease affecting humans. There are no therapeutics for the disease. We developed a novel virus neutralization assay, employing Ae. aegypti mosquitoes and viremic blood from dengue patients, to examine the virus-neutralizing potency of 12 human-derived monoclonal antibodies (mAbs) that had previously been shown to neutralize DENV in cell-culture systems. Five of the twelve mAbs failed to block dengue virus infections of mosquitoes using our assay. The remaining seven mAbs neutralized at least one serotype of dengue virus. The results demonstrate that some mAbs were functional and potently neutralized DENV in the complex matrix of viremic human blood. These findings advance the understanding of the types of antibodies that would be desirable to elicit using a dengue vaccine or to apply for acute therapy.