Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65 years of age and older: A phase II, observer-blind, randomized, controlled trial

Background: H7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7 subtype vaccine. Methods: 360 adults >= 65 years of age in stable health received either 1 of 4 adjuvanted A/mallard/ Netherlands/12/2000 split virion vaccine formulations (3.75 mu g or 7.5 mu g hemagglutinin adjuvanted with either AS03A or AS03(B)) or saline placebo, given as a 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays for the per-protocol cohort, comprising 332 participants at 21 days post-each dose, 332 at month 6, and 309 at month 12 (HI assay only). Safety was assessed up to month 12 for all participants who had received >= 1 dose (360 participants). Results: For H7N1 HI antibody assessment at day 42 (21 days post-dose 2), seroprotection rates (SPR) in the vaccinated groups were 69.6%-88.7%, seroconversion rates (SCR) 69.6%-88.5%, mean geometric increase (MGI) 11.0-18.9, and HI geometric mean titers (GMTs) 55.0-104.8. These parameters declined by month 6 and month 12. Microneutralization GMTs were 46.2-74.7 in the vaccinated groups at day 42, while vaccine response rate (VRR; proportion with >= 4-fold increase in MN titer) was 46.4%-81.5%. For the cross-reactive H7N9 strain, at day 42, HI GMT were 64.3-201.3, SPR 78.6%-96.3%, SCR 79.3%-96.3%, and MGI 14.1-37.7; MN GMTs were 44.0-85.6, and VRR 46.4-85.2%. The most frequent solicited symptom was injection site pain (41.7%-65.0% of vaccine recipients). In total, 40 participants reported 67 serious adverse events; none were considered causally related to vaccination. Conclusions: In adults aged >= 65 years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile. (C) 2017 GlaxoSmithKline. Published by Elsevier Ltd.