Affordable Access

Publisher Website

Introduction of mutations into the non-structural genes or 3′ untranslated region of an attenuated dengue virus type 4 vaccine candidate further decreases replication in rhesus monkeys while retaining protective immunity

Publication Date
DOI: 10.1016/j.vaccine.2004.02.031
  • Dengue
  • Vaccine
  • Mutagenesis
  • Biology


Abstract A dengue virus vaccine candidate, rDEN4Δ30, has been previously reported to be safe and immunogenic in humans, but a subset of vaccinees developed asymptomatic rash, elevation of liver enzymes and/or mild neutropenia. In the current study, mutations that had previously been shown to reduce replication of DEN4 virus in suckling mice and/or in SCID mice engrafted with human liver cells (SCID-HuH-7 mice) were introduced into rDEN4Δ30 in an attempt to further attenuate this virus. Three of the five resulting modified rDEN4Δ30 viruses showed decreased replication in SCID-HuH-7 mice relative to rDEN4Δ30. Moreover, in rhesus monkeys, two of the modified rDEN4Δ30 viruses showed a decrease in replication relative to rDEN4Δ30 while generating levels of neutralizing antibody similar to rDEN4Δ30 virus. All of the modified rDEN4Δ30 viruses completely protected immunized rhesus monkeys from challenge with wild-type DEN4 virus. Based on their attenuation for both human liver cells and rhesus monkeys, two of the modified rDEN4Δ30 vaccine candidates are currently being prepared for use in clinical trials. The application of these attenuating mutations to flavivirus vaccine development is discussed.

There are no comments yet on this publication. Be the first to share your thoughts.