title: Randomized comparison of the safety of Flublok(®) versus licensed inactivated influenza vaccine in healthy, medically stable adults ≥ 50 years of age.
abstract: BACKGROUND
  The safety and tolerability of Flublok(®), a purified recombinant hemagglutinin seasonal influenza vaccine, was compared to AFLURIA(®) in a randomized, blinded clinical trial in adults ≥ 50 years of age with attention to hypersensitivity reactions.
  
  
  METHODS
  This blinded, randomized trial of healthy adults ≥ 50 years of age compared safety of Flublok vs. AFLURIA with respect to pre-specified possible hypersensitivity: "rash," "urticaria," "swelling" and "non-dependent edema;" solicited reactogenicity and unsolicited adverse events. Subject-reported outcomes were collected for 30 days after vaccination. All adverse event terms were reviewed by physicians blinded to vaccine group, who added other terms possibly reflecting hypersensitivity. Case records of subjects with possible hypersensitivity were adjudicated by independent experts blinded to treatment assignment to identify likely hypersensitivity reactions. Non-inferiority of the incidence of hypersensitivity in the two vaccine groups was pre-defined as an absolute difference with an upper bound of 2-sided 95% confidence limits ≤ 0.015.
  
  
  RESULTS
  A total of 2640 subjects were enrolled, evenly split in age cohorts of 50-64 and ≥ 65 years. Fifty-two subjects reported at least one term possibly representing hypersensitivity, with a slight imbalance of 31 on Flublok and 21 on AFLURIA. The adjudicators determined that six and four subjects on Flublok and AFLURIA, respectively, likely met clinical criteria for hypersensitivity, yielding a difference in incidence between the two vaccine groups of 0.15% (upper bound of 2-sided 95% CI=0.9%). Reactogenicity and overall adverse event profiles were similar across both vaccines.
  
  
  CONCLUSIONS
  Flublok was non-inferior to AFLURIA in adults ≥ 50 years of age with respect to expert-adjudicated events of likely hypersensitivity during 30 days following vaccination (Sponsored by Protein Sciences Corporation; ClinicalTrials.gov number NCT01825200).
authors.affiliation: Protein Sciences Corporation, Meriden, CT, United States. Electronic address: rizikson@proteinsciences.com.
authors.forename: Ruvim
authors.initials: R
authors.lastname: Izikson
authors.affiliation: Yale University School of Medicine, New Haven, CT, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Leffell
authors.affiliation: University of Colorado Denver School of Medicine, Aurora, CO, United States.
authors.forename: S Allan
authors.initials: SA
authors.lastname: Bock
authors.affiliation: Biologics Consulting Group, Inc., Bethesda, MD, United States.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Patriarca
authors.affiliation: Protein Sciences Corporation, Meriden, CT, United States.
authors.forename: Penny
authors.initials: P
authors.lastname: Post
authors.affiliation: Protein Sciences Corporation, Meriden, CT, United States. Electronic address: ldunkle@proteinsciences.com.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Dunkle
authors.affiliation: Protein Sciences Corporation, Meriden, CT, United States.
authors.forename: Manon M J
authors.initials: MM
authors.lastname: Cox
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D007252:Influenza Vaccines / Q000009:adverse effects; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: Allergic reaction; Flublok; Influenza vaccine; Recombinant hemagglutinin vaccine