A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart

Abstract

A randomised, partially observer-blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart KG Participants: Three hundred and forty-seven subjects were identified and randomised to AS03 A -adjuvanted split-virion H1N1 vaccine or whole-virion (WV) vaccine in age groups [≥ 18-44 years (n = 140), ≥ 45-64 years (n = 136) and ≥ 65 years (n = 71)]. Interventions: Vaccine was administered by intramuscular injection into the deltoid muscle of the non-dominant arm. One hundred and seventy-five randomised subjects were allocated AS03 A -adjuvanted split H1N1 vaccine; one hundred and sixty-nine subjects had a second dose of the same vaccine 21 days later. One hundred and seventy-two subjects were allocated WV vaccine; one hundred and seventy-one subjects had a second dose of the same vaccine 21 days later. Serum samples for antibody measurements were collected on days 0 (before the first vaccination), 7, 14, 21 (before the second vaccination), 28, 35, 42 and 180. Subjects were observed for local and systemic reactions for 30 minutes after each injection, and for the next 7 days they recorded, in self-completed diaries, the severity of solicited local (pain, bruising, erythema and swelling) and systemic symptoms (chills, malaise, muscle aches, nausea and headache), oral temperature and use of analgesic medications. Main outcome measures: Vaccine immunogenicity using the CHMP and the FDA licensing criteria. Antibody titres were measured using haemagglutination inhibition (HI) and microneutralisation (MN) assays at baseline and 7, 14 and 21 days after each vaccination and at day 180. The three immunogenicity criteria end points were the seroprotection rate, the seroconversion rate and the mean-fold titre elevation. Results: Both vaccine doses were given in 340 subjects (98%). Data from 680 (99%) of 687 issued diary cards were returned. Sera were obtained from 340 (98.0%), 333 (96.0%), 341 (98.3%), 331 (95.4%), Abstract 196 329 (94.8%) and 332 (95.7%) subjects on days 7, 14, 21, 28, 35 and 42, respectively. Three hundred and fortysix and 345 subjects were included in the safety and immunogenicity analyses, respectively. Prevaccination antibody was detected by HI (titre ≥ 1 : 8) and MN (titre ≥ 1 : 10) in 14% and 31% of subjects, respectively. Among the 298 (85.9%) subjects without baseline antibody on HI assay, a titre of ≥ 1 : 40 (seroprotection) was achieved after a single dose of AS03 A -adjuvanted vaccine and WV vaccine by day 21 in 93.0% and 65.5%, respectively, of subjects between 18 and 44 years, 76.4% and 36.1% of subjects between 45 and 64 years, and 53.1% and 30.0% of subjects ≥ 65 years. Among all 347 subjects, a titre of ≥ 1 : 40 was achieved after a single dose of AS03 A -adjuvanted vaccine and WV vaccine by day 21 in 94.0% and 71.4%, respectively, of subjects between 18 and 44 years, 77.3% and 38.8% of subjects between 45 and 64 years, and 51.4% and 32.4% of subjects ≥ 65 years. The age-adjusted odds ratio (OR) for ...

Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults

“…Contrary to the observations made by Nicholson et al using a similar vaccine in adults including the elderly, 20 no age-related declined immunological response was observed at Day 42 in the present study, and the data indicated that the immunological response was persistent up to Month 6 in both age strata (20–40 and 41–64 y). The safety profile of the vaccine in Asian adults was comparable to previous reports and no-Asia-specific safety concerns were reported.…”

“…In addition, a large proportion of the participants were found to have protective levels of antibodies against the vaccine strain even six months after vaccination with two doses (although age-related decline was evident), indicating that pandemic influenza vaccines can potentially confer immunity against successive waves of the same virus 20 . This is in agreement with previous studies using the AS03-adjuvanted H1N1 2009 vaccine that have demonstrated substantial benefits in terms of induction of rapid, strong and long-lasting immune responses.…”

Adjustment for reporting bias in network meta-analysis of antidepressant trials

“…Reporting bias is a major threat to the validity of results of conventional systematic reviews or MAs [4,5]. Accounting for reporting biases in NMA is challenging, because unequal availability of findings across the network of evidence may jeopardize NMA validity [6,7].…”

Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals

“…Therefore, it was recommended for use by Health Canada in order to optimize vaccine efficacy and distribution in the Canadian population [4]. Immunogenicity of vaccine antigens is enhanced by inflammation [5-7] and clinical trial data indicates an increased incidence of non-severe vaccine-associated adverse events following administration of the ASO3 adjuvanted A/California/07/2009 H1N1 vaccine (Arepanrix TM ) compared to non-adjuvanted influenza antigen formulations [1,3,7]. These reported events were mainly symptoms of localized and systemic inflammation.…”