A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission fromvaccinees to mosquitoes

2A Delta 30 is a live dengue-4 virus vaccine candidate with a 30-nucleotide deletion in its 3'-untranslated region. To assess the transmissibility of 2A Delta 30 by mosquitoes, we compared its in vivo replication in mosquitoe s with that of its wild type DEN-4 parent. Both the vaccine candidate and w ild type virus were equally able to infect the mosquito Toxorhynchites sple ndens after intrathoracic inoculation. Relative to its wild type parent, 2A Delta 30 was slightly restricted in its ability to infect the midgut of Ae des aegypti mosquitoes fed on an artificial blood meal and was even more re stricted in its ability to disseminate from the midgut to the salivary glan ds. Thus, the 30-nucleotide deletion rendered the vaccine candidate more se nsitive than its wild type parent to the mosquito rnidgut escape barrier. M ost significantly, 2A Delta 30 was not transmitted to 352 Ae. albopictus mo squitoes fed on 10 vaccinees. all of whom were infected with the vaccine ca ndidate.