title: Safety, immunogenicity, and tolerability of three influenza vaccines in older adults: results of a randomized, controlled comparison.
abstract: To determine if newer influenza vaccines can safely improve seroprotection rates of older adults, we compared three licensed trivalent inactivated vaccines (TIVs) in a randomized, controlled trial with evaluator blinding. Participants were non-frail adults ≥ 65 y old, annually TIV-immunized. Study vaccines included intradermal (IDV), MF59-adjuvanted (ADV) and subunit (TIV) formulations of equal potency and strain composition. Blood was obtained before vaccination (V1) and 21 (V2) and 180 d (V3) afterward and tested by hemagglutination inhibition (HAI) assay. Safety diaries were completed daily by participants and specific tolerability questions were posed regarding injections and symptoms. In total, 911 participants were immunized and 887 (97.4%) completed V3. Groups had similar demographics. General symptom rates post-vaccination were similar among groups. Rates of injection site redness after IDV/ADV/TIV were 75%/13%/13% and rates of pain were 29%/38%/20%, respectively, but each vaccine was well tolerated, with symptoms causing little bother. Baseline antibody titers did not differ significantly among groups but B/Brisbane titers were too high for meaningful response assessments. At V2, seroprotection rates (HAI titer ≥ 40) were highest after ADV, the rate advantage over IDV and TIV being significant at 11.8% and 11.4% for H3N2 and 10.2% and 12.5% for H1N1, respectively. At day 180, seroprotection rates had declined ~25% and no longer differed significantly among groups. While IDV and TIV were also well tolerated, ADV induced modestly higher antibody titers in seniors to influenza A strains at 3 weeks but not 6 mo post-vaccination. Immune responses to IDV and TIV were similar in this population.
authors.affiliation: Vaccine Evaluation Center; University of British Columbia; Vancouver, BC Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Scheifele
authors.forename: Shelly A
authors.initials: SA
authors.lastname: McNeil
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.forename: Marc
authors.initials: M
authors.lastname: Dionne
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Brenda
authors.initials: B
authors.lastname: Coleman
authors.forename: Mark
authors.initials: M
authors.lastname: Loeb
authors.forename: Ethan
authors.initials: E
authors.lastname: Rubinstein
authors.forename: Janet
authors.initials: J
authors.lastname: McElhaney
authors.forename: Todd
authors.initials: T
authors.lastname: Hatchette
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Emanuele
authors.initials: E
authors.lastname: Montomoli
authors.forename: Amy
authors.initials: A
authors.lastname: Schneeberg
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bettinger
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D011446:Prospective Studies; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: adjuvant; adults; immunization; influenza; vaccine safety