Anuradha Madan1, Murdo Ferguson2, Paul Rheault3, David Seiden4, Azhar Toma5, Damien Friel6, Jyoti Soni7, Ping Li8, Bruce L Innis9, Anne Schuind10. 1. GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA. Electronic address: Anu.2.Madan@gsk.com. 2. Colchester Research Group, 68 Robie Street, Truro, Nova Scotia B2N 1L2, Canada. 3. Medicor Research Inc, 202-1280 Lasalle Blvd, Sudbury P3A 1Y8, Canada. 4. Broward Research Group, 7261 Sheridan Street, Suite 210, Hollywood 33024, USA. 5. Manna Research, 2291 Kipling Avenue Suite 117B, Toronto, Ontario M9W 4L6, Canada. Electronic address: azhar.toma@mannaresearch.com. 6. GSK, Avenue Fleming, 1300 Wavre, Belgium. Electronic address: damien.j.friel@gsk.com. 7. GSK, No. 5, Embassy, Bangalore 560052, India. 8. GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA. Electronic address: ping.li4@pfizer.com. 9. GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA. Electronic address: bruce.2.innis@gsk.com. 10. GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA.
Abstract
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 ≥65years of age in stable health received either1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3.75μg or 7.5μg hemagglutinin adjuvanted with either AS03A or AS03B) 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 21days 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 (21days 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 ≥65years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile. www.ClinicalTrials.gov: NCT01949090.
RCT Entities:
BACKGROUND: H7 influenza strains can cause severe and often fatal humaninfections, 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 ≥65years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3.75μg or 7.5μg hemagglutinin adjuvanted with either AS03A or AS03B) 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 21days 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 (21days 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 ≥65years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile. www.ClinicalTrials.gov: NCT01949090.
Authors: Patricia Winokur; Hana M El Sahly; Mark J Mulligan; Sharon E Frey; Richard Rupp; Evan J Anderson; Kathryn M Edwards; David I Bernstein; Kenneth Schmader; Lisa A Jackson; Wilbur H Chen; Heather Hill; Abigail Bellamy Journal: Vaccine Date: 2021-01-21 Impact factor: 3.641
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: Weina Sun; Stephen McCroskery; Wen-Chun Liu; Sarah R Leist; Yonghong Liu; Randy A Albrecht; Stefan Slamanig; Justine Oliva; Fatima Amanat; Alexandra Schäfer; Kenneth H Dinnon; Bruce L Innis; Adolfo García-Sastre; Florian Krammer; Ralph S Baric; Peter Palese Journal: Vaccines (Basel) Date: 2020-12-17