Phase II, randomized, double-blind, placebo-controlled, multicenter study to investigate the immunogenicity and safety of a West Nile virus vaccine in healthy adults

Abstract

Background: ChimeriVax-WN02 is a live, attenuated chimeric vaccine for protection against West Nile virus. This Phase II, randomized, double-blind, placebo-controlled, multicenter study assessed the immunogenicity, viremia, and safety of the ChimeriVax-WN02 vaccine.

Methods: The 2-part study included adults in general good health. In part 1, subjects aged 18-40 years were randomized to 1 of 4 treatment groups: ChimeriVax-WN02 3.7- × -10(5) plaque-forming units (PFU), 3.7 × 10(4) PFU, 3.7 × 10(3) PFU, or placebo. In part 2, subjects aged 41-64 and ≥ 65 years were randomized to receive ChimeriVax-WN02 3.7 × 10(5) PFU or placebo.

Results: In both part 1 and part 2, seroconversion was achieved at day 28 by >96% of subjects in active treatment groups. In part 1, neutralizing antibody titers at day 28 were higher and viremia levels lower with the highest dose, whereas the adverse event profile was similar between the dose groups. In part 2, antibody titers and viremia levels were higher in subjects aged ≥ 65 years, and more subjects in the 41-64 years cohort experienced adverse events.

Conclusions: The ChimeriVax-WN02 vaccine was highly immunogenic in younger adults and the elderly, and it was well tolerated at all dose levels and in all age groups investigated. Clinical Trials.gov identifier: NCT00442169.

Figures

Figure 1.

Flow of subjects through the study. a8 subjects at 1 study center were randomized to receive the low dose of ChimeriVax-WN02 (WN02) but actually received the medium dose of WN02 owing to a dilution error; bthis subject was included in the as treat per protocol (ATPP) population; cinclusion/exclusion criteria violation; dblood samples to test for yellow fever and St. Louis encephalitis viruses were taken before vaccination on day 0. N, number of subject; PFU, plaque-forming units.

Figure 1.

Flow of subjects through the study. a8 subjects at 1 study center were randomized to receive the low dose of ChimeriVax-WN02 (WN02) but actually received the medium dose of WN02 owing to a dilution error; bthis subject was included in the as treat per protocol (ATPP) population; cinclusion/exclusion criteria violation; dblood samples to test for yellow fever and St. Louis encephalitis viruses were taken before vaccination on day 0. N, number of subject; PFU, plaque-forming units.

Figure 2.

Seroconversion at day 28. All subjects had a prevaccination titer

Figure 3.

Mean viremia up to 14 days after injection. Viremia levels were determined by plaque assay on Vero cell monolayers using the crystal violet (negative stain) technique (part 1) or a positive staining (immunostain) technique (part 2) and defined as the mean number of plaque-forming units (PFU)/mL. WN02, ChimeriVax-WN02.