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

Vaccine. 2017 Apr 4;35(15):1865-1872. doi: 10.1016/j.vaccine.2017.02.057. Epub 2017 Mar 13.

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 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.

Keywords: AS03 adjuvant; Elderly population; H7 influenza vaccine; H7N1; H7N9; Pandemic flu.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • Drug Combinations
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Healthy Volunteers
  • Hemagglutination Inhibition Tests
  • Humans
  • Influenza A Virus, H7N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / immunology*
  • Male
  • Neutralization Tests
  • Placebos / administration & dosage
  • Polysorbates / administration & dosage*
  • Single-Blind Method
  • Squalene / administration & dosage*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / adverse effects
  • Vaccines, Inactivated / immunology
  • alpha-Tocopherol / administration & dosage*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Combinations
  • Influenza Vaccines
  • Placebos
  • Polysorbates
  • Vaccines, Inactivated
  • Squalene
  • AS03 adjuvant
  • alpha-Tocopherol

Associated data

  • ClinicalTrials.gov/NCT01949090