Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in healthy adults: A phase I/II, observer-blind, randomized, controlled trial. Issue 10 (7th March 2017)

• Record Type: Journal Article
• Authors: Madan, Anuradha; Ferguson, Murdo; Sheldon, Eric; Segall, Nathan; Chu, Laurence; Toma, Azhar; Rheault, Paul; Friel, Damien; Soni, Jyoti; Li, Ping; Innis, Bruce L.; Schuind, Anne
• Is Part Of: Vaccine. Volume 35:Issue 10(2017)
• Page Start: 1431
• Page End: 1439
• Publication Date: 2017-03-07
• Subjects: AE adverse event -- CBER Center for Biologics Evaluation and Research -- CHMP Committee for Medical Products for Human Use -- CI confidence interval -- GMT geometric mean titers -- HA hemagglutinin -- HI hemagglutination-inhibition -- MGI mean geometric increase -- MN microneutralization -- pIMD potential immune-mediated disease -- PP per-protocol -- RBC red blood cells -- SAE serious adverse event -- SAS statistical analysis system -- SBIR internet-based randomization system -- SCR seroconversion rate -- SPR seroprotection rate -- TVC total vaccinated cohort -- VRR vaccine response rate; H7N1 -- H7N9 -- Pandemic flu -- H7 influenza vaccine -- AS03 adjuvant; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.01.054
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Adjuvanted H7N1 vaccine formulations had a clinically acceptable safety profile. Beneficial AS03 adjuvant effect was demonstrated for all adjuvanted vaccine groups. Post-dose 2, all adjuvanted H7N1 formulations met regulatory acceptance criteria. Regulatory acceptance criteria were not met after 1 adjuvanted H7N1 vaccine dose. Cross-reactivity to the H7N9 virus was observed. Abstract: Background: H7 influenza strains have pandemic potential. AS03-adjuvanted H7N1 A/mallard/Netherlands/12/2000 split-virion vaccine formulations were evaluated as model H7-subtype vaccine and tested after H7N9 emerged in China, and caused severe human disease with high mortality. Methods: In this phase I/II, observer-blind, randomized trial in US and Canada, 420 healthy adults (21–64 years) were randomized to receive 1 of 4 H7N1 vaccine formulations (3.75 or 7.5 μg hemagglutinin adjuvanted with either AS03A or AS03B ), 15 μg unadjuvanted H7N1 hemagglutinin, or saline placebo, given as 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays, at day 42 (21 days post-dose 2), month 6, and month 12 (HI only) for the per-protocol cohorts (398, 379 and 368 participants, respectively). Safety is reported up to month 12. Results: Beneficial AS03 adjuvant effect was demonstrated. Committee for Medical Products for Human Use, and Center for Biologics Evaluation and Research (CBER) criteria were met for all adjuvanted formulations at day 42 (H7N1 HI assay); seroprotection (SPR) and seroconversion rates (SCR) were 88.5–94.8%, mean geometric increase (MGI) 19.2–34.9, and geometric mean titers (GMT) 98.3–180.7. Unadjuvanted H7N1 vaccine did not meet CBER criteria. In adjuvanted groups, antibody titers decreased over time; month 12 SPRs and GMTs were low (2.0–18.8% and 8.1–12.2). MN antibodies showed similar kinetics, with titers persisting at higher range than HI at month 6. All adjuvanted groups showed cross-reactivity against H7N9, with HI responses similar to H7N1. The most frequent solicited symptom in adjuvanted groups was injection site pain (71.2–86.7%); grade 3 solicited symptoms were infrequent. Nine participants reported 17 serious adverse events; none were considered causally related to vaccination. Conclusions: Adjuvanted H7N1 vaccine formulations had an acceptable safety profile and induced an antibody response after 2 doses with cross-reactivity to H7N9. ClinicalTrials.gov:NCT01934127