Priming Vaccination With Influenza Virus H5 Hemagglutinin Antigen Significantly Increases the Duration of T cell Responses Induced by a Heterologous H5 Booster Vaccination
H5N1 and other avian influenza strains represent major pandemic threats. Like all influenza A strains, H5N1 viruses evolve rapidly. Innovative immunization strategies are needed to induce cross-protective immunity.
Subjects primed with Clade 1 H5 antigen, with or without adjuvant, and H5 naïve 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.
Subjects previously vaccinated with Clade 1 H5 antigen developed significantly enhanced Clade 2 H5 cross-reactive T cell responses detectable 6 months post-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 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. Magnitude of CD4+ IFN-γ producing T cells correlated with H5 antibody responses.
H5 heterotypic priming prior to onset of an H5N1 pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus.
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