Priming Vaccination With Influenza Virus H5 Hemagglutinin Antigen Significantly Increases the Duration of T cell Responses Induced by a Heterologous H5 Booster Vaccination

J Infect Dis. 2016 Oct 1;214(7):1020-9. doi: 10.1093/infdis/jiw310. Epub 2016 Jul 20.


Background: Influenza A(H5N1) virus and other avian influenza virus strains represent major pandemic threats. Like all influenza A virus strains, A(H5N1) viruses evolve rapidly. Innovative immunization strategies are needed to induce cross-protective immunity.

Methods: Subjects primed with clade 1 H5 antigen, with or without adjuvant, and H5-naive individuals were boosted with clade 2 H5 antigen. The impact of priming on T cells capable of both proliferation and cytokine production after antigen restimulation was assessed.

Results: Subjects previously vaccinated with clade 1 H5 antigen developed significantly enhanced clade 2 H5 cross-reactive T cell responses detectable 6 months after vaccination with clade 2 H5 antigen. Priming dose (15 µg vs 45 or 90 µg) had no effect on magnitude of heterotypic H5 T cell responses. In contrast, age at priming negatively modulated both the magnitude and duration of heterotypic H5 T cell responses. Elderly subjects developed significantly less heterotypic H5 T cell boosting, predominantly for T cells capable of cytokine production. Adjuvant had a positive albeit weaker effect than age. The magnitude of CD4(+) interferon-γ producing T cells correlated with H5 antibody responses.

Conclusions: H5 heterotypic priming prior to onset of an A(H5N1) pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus.

Keywords: H5N1; clade; human; influenza; prime/boost; vaccine.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Proliferation
  • Cytokines / metabolism
  • Double-Blind Method
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / administration & dosage
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunity, Heterologous*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • Vaccination / methods*
  • Young Adult


  • Cytokines
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • hemagglutinin, avian influenza A virus