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

 Previous Article  |  Next Article 

Journal of Virology, January 2003, p. 1653-1657, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1653-1657.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Stephen S. Whitehead,1* Barry Falgout,2 Kathryn A. Hanley,1 Joseph E. Blaney, Jr.,1 Lewis Markoff,2 and Brian R. Murphy1

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 {Delta}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, rDEN1{Delta}30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4{Delta}30 vaccine candidate. rDEN1{Delta}30 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 rDEN1{Delta}30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1{Delta}30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the {Delta}30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the {Delta}30 mutation into wt DEN viruses belonging to each of the four serotypes.

* Corresponding author. Mailing address: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bldg. 50, Room 6515, 50 South Dr., Bethesda, MD 20892. Phone: (301) 496-7692. Fax: (301) 496-8312. E-mail: swhitehead{at}niaid.nih.gov.

Journal of Virology, January 2003, p. 1653-1657, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1653-1657.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»