Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 17, Pages 6694-6699Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0601932103
Keywords
clinical trial; non-human primate; yellow fever
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Funding
- NIAID NIH HHS [K08 AI001729, N01 AI025490, U19 AI057319, K08 AI01729] Funding Source: Medline
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West Nile (WN) virus is an important cause of febrile exanthem and encephalitis. Since it invaded the U.S. in 1999, > 19,000 human cases have been reported. The threat of continued epidemics has spurred efforts to develop vaccines. ChimeriVax-WNO2 is a live, attenuated recombinant vaccine constructed from an infectious clone of yellow fever (YF) 17D virus in which the premembrane and envelope genes of 17D have been replaced by the corresponding genes of WIN virus. Preclinical tests in monkeys defined sites of vaccine virus replication in vivo. ChimeriVax-WN02 and YF 17D had similar biodistribution but different multiplication kinetics. Prominent sites of replication were skin and lymphoid tissues, generally sparing vital organs. Viruses were cleared from blood by day 7 and from tissues around day 14. In a clinical study, healthy adults were inoculated with 5.0 log(10) plaque-forming units (PFU) (n = 30) or 3.0 log(10) PFU (n = 15) of ChimeriVax-WN02, commercial YF vaccine (YF-VAX, n = 5), or placebo (n = 30). The incidence of adverse events in subjects receiving the vaccine was similar to that in the placebo group. Transient viremia was detected in 42 of 45 (93%) of ChimeriVax-WN02 subjects, and four of five (80%) of YF-VAX subjects. All subjects developed neutralizing antibodies to WN or YF, respectively, and the majority developed specific T cell responses. ChimeriVax-WN02 rapidly elicits strong immune responses after a single dose, and is a promising candidate warranting further evaluation for prevention of WIN disease.
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