Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens

Vaccine. 2025 Feb 15:47:126689. doi: 10.1016/j.vaccine.2024.126689. Epub 2025 Jan 4.

Abstract

Introduction: Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans.

Material and methods: In a series of clinical trials, we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dose priming series had an appreciable effect on NAI antibody responses. Anti-HA stalk antibody responses were minimal and not durable.

Conclusions: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness.

Clinical trial registry numbers: NCT03312231, NCT03318315, NCT03589807, NCT03738241.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Drug Combinations
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus* / immunology
  • Humans
  • Immunization, Secondary / methods
  • Influenza A Virus, H7N9 Subtype* / immunology
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / immunology
  • Influenza, Human* / immunology
  • Influenza, Human* / prevention & control
  • Male
  • Middle Aged
  • Neuraminidase* / immunology
  • Polysorbates / administration & dosage
  • Squalene / administration & dosage
  • Squalene / immunology
  • Vaccines, Inactivated* / administration & dosage
  • Vaccines, Inactivated* / immunology
  • Young Adult
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / immunology

Substances

  • Influenza Vaccines
  • Antibodies, Viral
  • Neuraminidase
  • Vaccines, Inactivated
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Adjuvants, Immunologic
  • AS03 adjuvant
  • Polysorbates
  • alpha-Tocopherol
  • Squalene
  • Drug Combinations

Associated data

  • ClinicalTrials.gov/NCT03738241
  • ClinicalTrials.gov/NCT03318315
  • ClinicalTrials.gov/NCT03312231
  • ClinicalTrials.gov/NCT03589807