title: Safety and immunogenicity of 2010–2011 A/H1N1pdm09-containing trivalent inactivated influenza vaccine in adults previously given AS03-adjuvanted H1N1 2009 pandemic vaccine: results of a randomized trial.
abstract: Many Canadians received a novel AS03-adjuvanted vaccine during the 2009 influenza A/H1N1 pandemic. Longer term implications of adjuvant use were unclear: would anti-H1N1 immune responses persist at high levels and, if so, could that result in increased or unusual adverse effects upon re-exposure to H1N1pdm09 antigen in the trivalent influenza vaccine (TIV) for 2010-11? To answer these questions, adults given AS03-adjuvanted H1N1pdm09 vaccine (Arepanrix®, GSK Canada) 9-10 mo earlier were enrolled in an evaluator-blinded, crossover trial to receive 2010-2011 non-adjuvanted TIV (Fluviral®, GSK Canada) and placebo 10 d apart, in random order. Adverse effects were monitored for 7 d after each injection. Vaccine-attributable adverse event (VAAE) rates were calculated by subtracting rates after placebo from those after vaccine. Blood was obtained pre-vaccination and 21-30 d afterward to measure hemagglutination inhibiting antibody titers. In total, 326 participants were enrolled and 321 completed the study. VAAE rates were low except for myalgia (18.6%) and injection site pain (63.2%). At baseline, H1N1pdm09 titers ≥ 40 were present in 176/325 subjects (54.2%, 95% confidence interval 48.6, 59.7), with a geometric mean titer (GMT) of 37.4 (95% CI 32.8, 42.6). Post-immunization, 96.0% (95% CI 92.3, 97.8) had H1N1pdm09 titers ≥ 40, with GMT of 167.4 (95% CI 148.7, 188.5). Responses to both influenza A strains in TIV were similar, implying no lasting effect of adjuvant exposure. In summary, titers ≥ 40 persisted in only half the participants 9-10 mo after adjuvanted pandemic vaccine but were restored in nearly all after TIV vaccination, with minimal increase in adverse effects.
authors.affiliation: Vaccine Evaluation Center, BC Children’s Hospital, University of British Columbia, Vancouver, BC Canada. dscheifele@cfri.ca
authors.forename: David W
authors.initials: DW
authors.lastname: Scheifele
authors.forename: Marc
authors.initials: M
authors.lastname: Dionne
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Otto G
authors.initials: OG
authors.lastname: Vanderkooi
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002170:Canada; D018592:Cross-Over Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects* / Q000379:methods*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D010919:Placebos; D015164:Vaccines, Inactivated