The live attenuated chimeric vaccine rWN/DEN4δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers

Anna P. Durbin, Peter F. Wright, Amber Cox, Eunice Wangeci Kagucia, Daniel Elwood, Susan Henderson, Kimberli Wanionek, Jim Speicher, Stephen S. Whitehead, Alexander G. Pletnev

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


WNV has become the leading vector-borne cause of meningoencephalitis in the United States. Although the majority of WNV infections result in asymptomatic illness, approximately 20% of infections result in West Nile fever and 1% in West Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or flaccid paralysis. The elderly are at particular risk for WNND, with more than half the cases occurring in persons older than sixty years of age. There is no licensed treatment for WNND, nor is there any licensed vaccine for humans for the prevention of WNV infection. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a recombinant live attenuated WNV vaccine based on chimerization of the wild-type WNV NY99 genome with that of the live attenuated DENV-4 candidate vaccine rDEN4δ30. The genes encoding the prM and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the resultant virus was designated rWN/DEN4δ30. The vaccine was evaluated in healthy flavivirus-naïve adult volunteers age 18-50 years in two separate studies, both of which are reported here. The first study evaluated 103 or 104PFU of the vaccine given as a single dose; the second study evaluated 105PFU of the vaccine given as two doses 6 months apart. The vaccine was well-tolerated and immunogenic at all three doses, inducing seroconversion to WNV NY99 in 74% (103PFU), 75% (104PFU), and 55% (105PFU) of subjects after a single dose. A second 105PFU dose of rWN/DEN4δ30 given 6 months after the first dose increased the seroconversion rate 89%. Based on the encouraging results from these studies, further evaluation of the candidate vaccine in adults older than 50 years of age is planned.

Original languageEnglish (US)
Pages (from-to)5772-5777
Number of pages6
Issue number48
StatePublished - Nov 19 2013


  • Clinical trial
  • Live attenuated WNV vaccine
  • West Nile virus (WNV)

ASJC Scopus subject areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


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