Infection of Aedes albopictus and Aedes aegypti mosquitoes with dengue parent and progeny candidate vaccine viruses: a possible marker of human attenuation.

Dengue (DEN-1) and DEN-4 parent (P) and progeny candidate vaccine (CV) viruses were compared in their abilities to infect and to replicate in Aedes aegypti and Aedes albopictus mosquitoes. The DEN CV clones were temperature sensitive (ts) and had small plaque morphology. The DEN-1 and DEN-4 CV viruses differed in their ability to infect, to replicate in, and to be transmitted by mosquitoes. The DEN-1 CV virus was not attenuated for the vector mosquitoes; oral infection rates with the CV virus were as high as or higher than the P virus, and the CV virus replicated efficiently in mosquitoes after oral infection. The DEN-4 CV virus was attenuated; it was less efficient than its P virus in infection and replication in mosquitoes. Thus, the ts phenotype and small plaque morphology are not reliable biological markers for prediction of vector attenuation. Similar results were reported by others for attenuation in man and monkeys. These studies with DEN-1 and DEN-4 viruses, and previously reported studies with DEN-2 virus and with DEN-3 virus suggest that vector and vertebrate host attenuation are genetically linked. Thus, vector attenuation may be a biological marker for human attenuation.