This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Whitehead, S. S. Articles by Murphy, B. R. Search for Related Content PubMed PubMed Citation Articles by Whitehead, S. S. Articles by Murphy, B. R.

A Live, Attenuated Dengue Virus Type 1 Vaccine Candidate with a 30-Nucleotide Deletion in the 3' Untranslated Region Is Highly Attenuated and Immunogenic in Monkeys

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health,¹ Laboratory of Vector-Borne Virus Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892²

Received 8 August 2002/ Accepted 8 October 2002

The 30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN130, was attenuated in rhesus monkeys to a level similar to that of the rDEN430 vaccine candidate. rDEN130 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN130 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN130 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the 30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the 30 mutation into wt DEN viruses belonging to each of the four serotypes.