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, Daniel F; Lottenbach, Kathleen; Goll, Johannes B; Hill, Heather; Winokur, Patricia L; Patel, Shital M; Brady, Rebecca C; Chen, Wilbur H; Edwards, Kathryn; Creech, C Buddy; Frey, Sharon E; Blevins, Tamara P; Salomon, Rachelle; Belshe, Robert B
J Infect Dis
Date Published
2016 10 01
Adult; Aged; Aged, 80 and over; Cell Proliferation; Cytokines; Double-Blind Method; Female; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Immunity, Heterologous; Influenza Vaccines; Influenza, Human; Male; Middle Aged; T-Lymphocytes; Vaccination; Young Adult

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.