title: Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65years of age and older: A phase II, observer-blind, randomized, controlled trial.
abstract: 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.
  
  
  
  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 AS03Aor 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).
  
  
  
  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.
  
  
  
  In adults aged ≥65years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile. www.ClinicalTrials.gov: NCT01949090.
authors.affiliation: GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA. Electronic address: Anu.2.Madan@gsk.com.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Madan
authors.affiliation: Colchester Research Group, 68 Robie Street, Truro, Nova Scotia B2N 1L2, Canada.
authors.forename: Murdo
authors.initials: M
authors.lastname: Ferguson
authors.affiliation: Medicor Research Inc, 202-1280 Lasalle Blvd, Sudbury P3A 1Y8, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Rheault
authors.affiliation: Broward Research Group, 7261 Sheridan Street, Suite 210, Hollywood 33024, USA.
authors.forename: David
authors.initials: D
authors.lastname: Seiden
authors.affiliation: Manna Research, 2291 Kipling Avenue Suite 117B, Toronto, Ontario M9W 4L6, Canada. Electronic address: azhar.toma@mannaresearch.com.
authors.forename: Azhar
authors.initials: A
authors.lastname: Toma
authors.affiliation: GSK, Avenue Fleming, 1300 Wavre, Belgium. Electronic address: damien.j.friel@gsk.com.
authors.forename: Damien
authors.initials: D
authors.lastname: Friel
authors.affiliation: GSK, No. 5, Embassy, Bangalore 560052, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Soni
authors.affiliation: GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA. Electronic address: ping.li4@pfizer.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA. Electronic address: bruce.2.innis@gsk.com.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
authors.affiliation: GSK, 2301 Renaissance Blvd, RN0220, King of Prussia, PA 19406, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Schuind
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D057916:Influenza A Virus, H7N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D010919:Placebos / Q000008:administration & dosage; D011136:Polysorbates / Q000008:administration & dosage*; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D010919:Placebos; D011136:Polysorbates; D015164:Vaccines, Inactivated; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
keywords: AS03 adjuvant; Elderly population; H7 influenza vaccine; H7N1; H7N9; Pandemic flu