Chimeric Langat/Dengue viruses protect mice from heterologous challenge with the highly virulent strains of tick-borne encephalitis virus

Langat virus (LGT), a tick-borne flavivirus, is naturally attenuated for hu mans but it is very virulent in SCID mice. In contrast, viable recombinant chimeras of LGT (preM and E genes) and dengue type 4 virus (all other seque nces) recovered in mosquito cell culture were completely attenuated in SCID mice but still capable of providing protection against LGT. To develop the chimeras into Vaccine candidates, we adapted them to replicate efficiently in simian Vero cells, a satisfactory substrate for human vaccines. The ada pted chimeras remained completely attenuated for SCID mice and, significant ly provided protection in immunocompetent mice against tick-borne encephali tis virus, the most virulent of the tick-borne flaviviruses. (C) 2000 Acade mic Press.