Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection
Kimberly Page, Michael T. Melia, Rebecca T. Veenhuis, Matthew E. Winter, Kimberly E. Rousseau, Guido Massaccesi, William O. Osburn, Michael Forman, E. Donnall Thomas, Karla Thornton, Katherine Wagner, Ventzislav Vassilev, Lan Lin, Paula J. Lum, Linda C. Giudice, Ellen Stein, Alice Asher, Soju Chang, Richard L. Gorman, Marc G. Ghany, T. Jake Liang, Michael R. Wierzbicki, Elisa Scarselli, Alfredo Nicosia, Antonella Folgori, Stefania Capone, Andrea L. Cox
Abstract
BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.).