Immunogenicity and Safety of AS03-Adjuvanted H7N9 Influenza Vaccine in Adults (18-64 and ≥65 Years): A Phase 1/2, Randomized, Placebo-Controlled Trial

Influenza Other Respir Viruses. 2024 Dec;18(12):e70020. doi: 10.1111/irv.70020.

Abstract

Background: Influenza A/Hong Kong/125/2017 (H7N9) virus poses a pandemic risk owing to its evolving nature. This study evaluated the immunogenicity and safety of an AS03-adjuvanted H7N9 vaccine in adults (18-64 years [younger] and ≥65 years [older]).

Methods: Participants (younger, n = 418; older, n = 420) were randomized to receive one of six adjuvanted vaccines (hemagglutinin [1.9 μg, 3.75 μg, and 7.5 μg] with AS03A or AS03B) or placebo. The co-primary objectives were to determine whether the adjuvanted vaccines elicit an immune response against the vaccine-homologous virus 21 days after the second vaccine dose and to evaluate the safety of the vaccines.

Results: H7N9 AS03-adjuvanted vaccines at various doses showed a humoral immune response but failed to meet CBER immunogenicity criteria. However, a trend of increased immune responses was observed with the AS03A adjuvant versus the AS03B adjuvant, particularly in older adults. In both age groups, injection site pain and fatigue occurred more frequently with adjuvanted vaccines. No reported serious adverse events were vaccine-related.

Conclusions: This study did not achieve its primary objective at any dose level. The modest immune response to AS03-adjuvanted vaccines, consistent with other studies using similar antigens, highlights the need for continued research for H7N9 pandemic preparedness.

Trial registration: NCT04789577 [ClinicalTrials.gov].

Keywords: AS03; H7N9; influenza; vaccine.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Vaccine / administration & dosage
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral* / blood
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Influenza A Virus, H7N9 Subtype* / immunology
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / adverse effects
  • Influenza Vaccines* / immunology
  • Influenza, Human* / immunology
  • Influenza, Human* / prevention & control
  • Male
  • Middle Aged
  • Polysorbates / administration & dosage
  • Squalene / administration & dosage
  • Squalene / immunology
  • Young Adult
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / adverse effects
  • alpha-Tocopherol / immunology

Substances

  • Influenza Vaccines
  • Antibodies, Viral
  • AS03 adjuvant
  • Adjuvants, Vaccine
  • Squalene
  • Polysorbates
  • Adjuvants, Immunologic
  • alpha-Tocopherol
  • Drug Combinations

Associated data

  • ClinicalTrials.gov/NCT04789577