title: Short-Term Immunogenicity and Safety of an Accelerated Pre-Exposure Prophylaxis Regimen With Japanese Encephalitis Vaccine in Combination With a Rabies Vaccine: A Phase III, Multicenter, Observer-Blind Study.
abstract: BACKGROUND
  The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study.
  
  
  METHODS
  Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57.
  
  
  RESULTS
  Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine.
  
  
  CONCLUSIONS
  This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated regimen, if licensed, could potentially be a valid alternative for individuals requiring a primary series of JE vaccination and rabies pre-exposure prophylaxis on short notice.
authors.affiliation: The Berlin Center for Travel and Tropical Medicine, Berlin, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelinek
authors.affiliation: Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Gerd D
authors.initials: GD
authors.lastname: Burchard
authors.affiliation: Institute of Tropical Medicine and International Health, Charité, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dieckmann
authors.affiliation: Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Silja
authors.initials: S
authors.lastname: Bühler
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Paulke-Korinek
authors.affiliation: Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Nothdurft
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, Rostock University Medical Center, Rostock, Germany.
authors.forename: Emil
authors.initials: E
authors.lastname: Reisinger
authors.affiliation: Novartis Healthcare Pvt. Ltd., Hyderabad, India.
authors.forename: Khaleel
authors.initials: K
authors.lastname: Ahmed
authors.affiliation: Novartis Vaccines and Diagnostics, GmbH, Marburg, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Bosse
authors.affiliation: Novartis Vaccines and Diagnostics, GmbH, Marburg, Germany.
authors.forename: Seetha
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Novartis Vaccines and Diagnostics, S.r.l., Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Costantini
authors.affiliation: Novartis Vaccines and Diagnostics, S.r.l., Siena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Pellegrini
mesh_terms: D000328:Adult; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D006801:Humans; D055261:Immunogenetic Phenomena / Q000187:drug effects*; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000276:immunology; D008875:Middle Aged; D009500:Neutralization Tests / Q000379:methods; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors; D014195:Travel; D057236:Travel Medicine / Q000379:methods; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
chemical_list: D022321:Japanese Encephalitis Vaccines; D011819:Rabies Vaccines