A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults

Clin Infect Dis. 2024 Jun 14;78(6):1757-1768. doi: 10.1093/cid/ciae173.

Abstract

Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.

Methods: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed.

Results: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval.

Conclusions: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.

Keywords: 2013 H7N9; 2017 H7N9; antibody; avian influenza; boost.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Vaccine / administration & dosage
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral* / blood
  • Drug Combinations
  • Female
  • Healthy Volunteers
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunization Schedule
  • Immunization, Secondary*
  • 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
  • Polysorbates / adverse effects
  • Squalene / administration & dosage
  • Squalene / adverse effects
  • Squalene / immunology
  • Vereinigte Staaten
  • Vaccination / methods
  • Vaccines, Inactivated* / administration & dosage
  • Vaccines, Inactivated* / adverse effects
  • Vaccines, Inactivated* / immunology
  • Young Adult
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / adverse effects

Substances

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

Associated data

  • ClinicalTrials.gov/NCT03589807