title: A serum-free, purified vero cell rabies vaccine is safe and as immunogenic as the reference vaccine Verorab for pre-exposure use in healthy adults: results from a randomized controlled phase-II trial.
abstract: BACKGROUND
  Verorab was licensed in 1985 for both pre- and post-exposure prophylaxis of rabies. The next generation purified Vero cell rabies vaccine (PVRV-NG) is a highly purified vaccine. We performed a phase II clinical study in adults in France to assess its immunological non-inferiority and clinical safety for pre-exposure prophylaxis.
  
  
  METHODS
  In a randomized phase-II trial, 384 healthy adult subjects were randomized (2:1) to receive a three-dose primary series of PVRV-NG or Verorab. One year later, the PVRV-NG group received a PVRV-NG booster while the Verorab group participants were randomized to receive a booster of PVRV-NG or Verorab for. Rabies virus neutralizing antibodies (RVNA) were evaluated on days 0, 28 (subgroup), 42, months 6, 12 and 12+14 days. Safety was evaluated for seven days after each dose. Adverse event between doses, until 28 days after the final dose was recorded. Serious adverse events were recorded up to 6 months after the last dose.
  
  
  RESULTS
  The criterion for non-inferiority was met in the per-protocol analysis set and confirmed in the full analysis set (FAS). In the FAS, 99.6% and 100% of subjects had RVNA titers ≥0.5 IU/mL in PVRV-NG and Verorab groups, respectively. While RVNA levels gradually decreased over the 12-month period, at 6 and 12 months after vaccination >89% and >77%, respectively, in both groups had RVNA titers ≥0.5 IU/mL. The PVRV-NG booster induced a strong response, irrespective of the vaccine given for the primary series. PVRV-NG was safe and well tolerated and its safety profile was similar to Verorab for unsolicited adverse events and solicited systemic reactions. The incidence of solicited injection-site reactions was lower with PVRV-NG than with Verorab after the primary series and the booster dose.
  
  
  CONCLUSIONS
  PVRV-NG was shown to be at least as immunogenic as Verorab and to present a similar safety profile.
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France. Sylvie.Pichon@sanofipasteur.com
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pichon
authors.forename: Françoise
authors.initials: F
authors.lastname: Guinet-Morlot
authors.forename: Maria
authors.initials: M
authors.lastname: Minutello
authors.forename: Yves
authors.initials: Y
authors.lastname: Donazzolo
authors.forename: Regine
authors.initials: R
authors.lastname: Rouzier
authors.forename: Didier
authors.initials: D
authors.lastname: Chassard
authors.forename: Serge
authors.initials: S
authors.lastname: Fitoussi
authors.forename: Victor
authors.initials: V
authors.lastname: Hou
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D005260:Female; D005602:France; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology; D014709:Vero Cells; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011819:Rabies Vaccines