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. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that mAbs can neutralize infectious DENV derived from infected human cells, in the matrix of human blood. Coupled with previous evidence of their ability to prevent DENV infection of mammalian cells, such mAbs could be considered attractive antibody classes to elicit with dengue vaccines, or alternatively, for consideration as therapeutic candidates.

Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes.

The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.

Comparative Susceptibility of Aedes albopictus and Aedes aegypti to Dengue Virus Infection After Feeding on Blood of Viremic Humans: Implications for Public Health.

Aedes albopictus is secondary to Aedes aegypti as a vector of dengue viruses (DENVs) in settings of endemicity, but it plays an important role in areas of dengue emergence. This study compared the susceptibility of these 2 species to DENV infection by performing 232 direct blood-feeding experiments on 118 viremic patients with dengue in Vietnam. Field-derived A. albopictus acquired DENV infections as readily as A. aegypti after blood feeding. Once infected, A. albopictus permitted higher concentrations of DENV RNA to accumulate in abdominal tissues, compared with A. aegypti. However, the odds of A. albopictus having infectious saliva were lower than the odds observed for A. aegypti (odds ratio, 0.70; 95% confidence interval, .52-.93). These results quantitate the susceptibility of A. albopictus to DENV infection and will assist parameterization of models for predicting disease risk in settings where A. albopictus is present.

Host and viral features of human dengue cases shape the population of infected and infectious Aedes aegypti mosquitoes.

Dengue is the most prevalent arboviral disease of humans. The host and virus variables associated with dengue virus (DENV) transmission from symptomatic dengue cases (n = 208) to Aedes aegypti mosquitoes during 407 independent exposure events was defined. The 50% mosquito infectious dose for each of DENV-1-4 ranged from 6.29 to 7.52 log10 RNA copies/mL of plasma. Increasing day of illness, declining viremia, and rising antibody titers were independently associated with reduced risk of DENV transmission. High early DENV plasma viremia levels in patients were a marker of the duration of human infectiousness, and blood meals containing high concentrations of DENV were positively associated with the prevalence of infectious mosquitoes 14 d after blood feeding. Ambulatory dengue cases had lower viremia levels compared with hospitalized dengue cases but nonetheless at levels predicted to be infectious to mosquitoes. These data define serotype-specific viremia levels that vaccines or drugs must inhibit to prevent DENV transmission.