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

Publication Type
Journal Article
Year of Publication
Hoft, DF; Lottenbach, K; Goll, JB; Hill, H; Winokur, PL; Patel, SM; Brady, RC; Chen, WH; Edwards, K; Creech, CB; Frey, SE; Blevins, TP; Salomon, R; Belshe, RB
J Infect Dis
Start Page
Date Published
clade; H5n1; Human; influenza; prime/boost; vaccine

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.