title: Safety and immunogenicity of an inactivated whole virus Vero cell-derived Ross River virus vaccine: a randomized trial.
abstract: BACKGROUND
  Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. Approximately 5000 cases of RRV disease, which is characterized by debilitating polyarthritis, are recorded each year in Australia. This study describes the first clinical trial of a candidate RRV vaccine.
  
  
  METHODS
  An inactivated whole-virus Vero cell-derived RRV vaccine was tested in 382 healthy, RRV-naïve adults in a phase 1/2 dose-escalation study at ten sites in Austria, Belgium and The Netherlands. Subjects were equally randomized to receive 1.25 μg, 2.5 μg, 5 μg, or 10 μg aluminum hydroxide-adjuvanted or non-adjuvanted RRV vaccine, with a second dose after three weeks and a booster at six months. Vaccine immunogenicity was determined by measurements of serum IgG and neutralizing antibody titers. Vaccine tolerability and safety were monitored over the entire study period.
  
  
  RESULTS
  The optimal vaccine formulation was the adjuvanted 2.5 μg dose, as calculated using a repeated mixed model analysis of covariance comparing log-transformed RRV-specific IgG titers between different dose groups. Geometric means of RRV-specific serum antibodies measured 21 days after the third vaccination with the 2.5 μg adjuvanted formulation were 520.9 (90% CI 377.2-719.4) as determined by IgG ELISA and 119.9 (82.6-173.9) as determined by virus neutralization assay, resulting in seropositivity rates of 92.9% (82.6-98.0) and 92.7% (82.2-98.0), respectively. All vaccine formulations and doses were well tolerated after the first, second and third vaccination.
  
  
  CONCLUSIONS
  The adjuvanted, inactivated whole-virus Vero cell-derived Ross River virus vaccine is highly immunogenic in RRV-naïve adults and well tolerated at all dose levels.
authors: Global R&D, Baxter BioScience, IZD Tower, Wagramerstraße 17-19, A-1220 Vienna, Austria. gerald aichinger@baxter.com
authors: Gerald
authors: G
authors: Aichinger
authors: Hartmut J
authors: HJ
authors: Ehrlich
authors: John G
authors: JG
authors: Aaskov
authors: Sandor
authors: S
authors: Fritsch
authors: Christiane
authors: C
authors: Thomasser
authors: Wolfgang
authors: W
authors: Draxler
authors: Michael
authors: M
authors: Wolzt
authors: Markus
authors: M
authors: Müller
authors: Fritz
authors: F
authors: Pinl
authors: Pierre
authors: P
authors: Van Damme
authors: Annick
authors: A
authors: Hens
authors: Jack
authors: J
authors: Levy
authors: Daniel
authors: D
authors: Portsmouth
authors: Georg
authors: G
authors: Holzer
authors: Otfried
authors: O
authors: Kistner
authors: Thomas R
authors: TR
authors: Kreil
authors: P Noel
authors: PN
authors: Barrett
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D018354:Alphavirus Infections / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001317:Austria; D001530:Belgium; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D009426:Netherlands; D009500:Neutralization Tests; D012398:Ross River virus / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D015164:Vaccines, Inactivated; D014765:Viral Vaccines