Anuradha Madan1, Murdo Ferguson2, Eric Sheldon3, Nathan Segall4, Laurence Chu5, Azhar Toma6, Paul Rheault7, Damien Friel8, Jyoti Soni9, Ping Li10, Bruce L Innis11, Anne Schuind12. 1. GSK, 1250 South Collegeville Road, Collegeville, PA 19426, USA. Electronic address: Anu.2.Madan@gsk.com. 2. Colchester Research Group, 68 Robie Street, Truro, Nova Scotia B2N 1L2, Canada. 3. Miami Research Associates, 6141 Sunset Drive Suite 501, Miami 33143, USA. 4. Clinical Research Atlanta, 175 Country Club Dr. Ste A, Stockbridge 30281, USA. 5. Benchmark Research, 1015 East 32nd Street, Suite 309, Austin, TX 78705, USA. 6. Manna Research, 2291 Kipling Avenue Suite 117B, Toronto, Ontario M9W 4L6, Canada. Electronic address: azhar.toma@mannaresearch.com. 7. Medicor Research Inc, 202-1280 Lasalle Blvd, Sudbury, Ontario P3E 1H5, Canada. 8. GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. 9. GSK Pharmaceuticals Ltd., 5 Embassy Links, SRT Road, Bangalore, India. 10. GSK, 2301 Renaissance Blvd, King of Prussia, PA 19406-2772, USA. Electronic address: ping.li4@pfizer.com. 11. GSK, 14200 Shady Grove Road, Rockville, MD 20850, USA. 12. GSK, 2301 Renaissance Blvd, King of Prussia, PA 19406-2772, USA.
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 (21-64years) were randomized to receive 1 of 4 H7N1 vaccine formulations (3.75 or 7.5μg hemagglutinin adjuvanted with either AS03A or AS03B), 15μg 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 (21days 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.
RCT Entities:
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 (21-64years) were randomized to receive 1 of 4 H7N1 vaccine formulations (3.75 or 7.5μg hemagglutinin adjuvanted with either AS03A or AS03B), 15μg 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 (21days 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.
Authors: Christine M Oshansky; James King; Di Lu; James Zhou; Corrina Pavetto; Gary Horwith; Karen Biscardi; Bai Nguyen; John J Treanor; Li-Mei Chen; Brett Jepson; Rick A Bright; Robert A Johnson; Vittoria Cioce; Ruben O Donis Journal: NPJ Vaccines Date: 2021-03-19 Impact factor: 7.344
Authors: Wivine Burny; Andrea Callegaro; Viviane Bechtold; Frédéric Clement; Sophie Delhaye; Laurence Fissette; Michel Janssens; Geert Leroux-Roels; Arnaud Marchant; Robert A van den Berg; Nathalie Garçon; Robbert van der Most; Arnaud M Didierlaurent Journal: Front Immunol Date: 2017-08-14 Impact factor: 7.561