title: One-year immunogenicity kinetics and safety of a purified chick embryo cell rabies vaccine and an inactivated Vero cell-derived Japanese encephalitis vaccine administered concomitantly according to a new, 1-week, accelerated primary series.
abstract: BACKGROUND
  Conventional rabies pre-exposure prophylaxis (PrEP) and Japanese encephalitis (JE) primary series vaccination regimens each require up to 4 weeks to complete and, thus, may not be feasible for individuals who need these immunizations on short notice. This Phase 3b, randomized, controlled, observer-blind study evaluated the immunogenicity and safety of concomitant administration of a purified chick embryo cell culture rabies vaccine and an inactivated, adsorbed JE vaccine according to an accelerated (1 week) regimen when compared with the conventional regimens (4 weeks). This report describes the kinetics of immune responses up to 1 year after vaccination.
  
  
  METHODS
  A total of 661 healthy adults (18 to ≤65 years) were randomized into the following accelerated or conventional vaccine regimens: Rabies + JE-Conventional, Rabies + JE-Accelerated, Rabies-Conventional and JE-Conventional. Immunogenicity was assessed by virus neutralization tests. Safety and tolerability were also evaluated.
  
  
  RESULTS
  Irrespective of rabies vaccination regimen, ≥97% of subjects had adequate levels of rabies virus neutralizing antibody (RVNA) concentrations (≥0.5 IU/ml) up to Day 57, with percentages of subjects with RVNA concentrations ≥0.5 IU/ml at Day 366 ranging between 68% in the Rabies + JE-Accelerated group and 80% of subjects in the Rabies-Conventional group. The Rabies + JE-Accelerated group revealed high JE neutralizing antibody titers at all-time points. At Day 366, the percentage of subjects with antibody titers indicative of seroprotection (PRNT50 titers ≥1:10) remained high across JE vaccine groups (86-94%).
  
  
  CONCLUSIONS
  The accelerated PrEP rabies and JE vaccination regimens, once licensed, could represent a valid alternative in the short-term to currently recommended conventional regimens. The concomitant administration of these two vaccines does not compromise immune responses to any of the vaccine antigens particularly when aiming for short-term protection. Further evidence will clarify the need for and timing to administration of rabies vaccine booster doses in subjects primed with an accelerated PrEP regimen. (NCT01662440).
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Section Clinical Research and Epidemiology/University Medical Center Hamburg-Eppendorf, Bernhard Nocht Centre for Clinical Trials (BNCCT), Hamburg, Germany.
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Cramer
authors.affiliation: Berlin Center for Travel and Tropical Medicine, Berlin, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelinek
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Medical University Vienna, Austria, Federal Ministry of Health, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Paulke-Korinek
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, University of Rostock Medical School, Rostock, Germany.
authors.forename: Emil C
authors.initials: EC
authors.lastname: Reisinger
authors.affiliation: Institute of Tropical Medicine and International Health, Charité-Universitaetsmedizin Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dieckmann
authors.affiliation: Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Alberer
authors.affiliation: Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
authors.forename: Silja
authors.initials: S
authors.lastname: Bühler
authors.affiliation: Novartis Vaccines and Diagnostics, GmbH, Marburg, Germany (a GSK company) and.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Bosse
authors.affiliation: Novartis Vaccines and Diagnostics, GmbH, Marburg, Germany (a GSK company) and.
authors.forename: Seetha
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Novartis Vaccines and Diagnostics, Srl (a GSK company), Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Fragapane
authors.affiliation: Novartis Vaccines and Diagnostics, Srl (a GSK company), Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Costantini
authors.affiliation: Novartis Vaccines and Diagnostics, Srl (a GSK company), Siena, Italy michele.x.pellegrini@gsk.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Novartis Vaccines and Diagnostics, Srl (a GSK company), Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Lattanzi
authors.affiliation: Novartis Vaccines and Diagnostics, Srl (a GSK company), Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dovali
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001317:Austria; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004311:Double-Blind Method; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D005260:Female; D005858:Germany; D006801:Humans; D007117:Immunization, Secondary; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D013557:Switzerland; D014195:Travel; D014709:Vero Cells / Q000821:virology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; D011819:Rabies Vaccines
keywords: Accelerated vaccination; Japanese encephalitis vaccine; concomitant vaccination; persistence; rabies vaccine; travelers on short notice