Journal Article

Adjuvanted H5N1 vaccine induces early CD4⁺ T cell response that predicts long-term persistence of protective antibody levels

Del Giudice, Giuseppe, Sammicheli, Chiara, Nuti, Sandra, Borgogni, Erica, Tavarini, Simona, Rappuoli, Rino, Castellino, Flora, Zedda, Luisanna, Brauer, Volker, Banzhoff, Angelika, Galli, Grazia, Malzone, Carmine, Bardelli, Monia, Hilbert, Anne K, Medini, Duccio

2009

Overview

Immune responses to vaccination are tested in clinical trials. This process usually requires years especially when immune memory and persistence are analyzed. Markers able to quickly predict the immune response would be very useful, particularly when dealing with emerging diseases that require a rapid response, such as avian influenza. To address this question we vaccinated healthy adults at days 1, 22, and 202 with plain or MF59-adjuvanted H5N1 subunit vaccines and tested both cell-mediated and antibody responses up to day 382. Only the MF59-H5N1 vaccine induced high titers of neutralizing antibodies, a large pool of memory H5N1-specific B lymphocytes, and H5-CD4⁺ T cells broadly reactive with drifted H5. The CD4⁺ response was dominated by IL-2⁺ IFN-γ⁻ IL-13⁻ T cells. Remarkably, a 3-fold increase in the frequency of virus-specific total CD4⁺ T cells, measurable after 1 dose, accurately predicted the rise of neutralizing antibodies after booster immunization and their maintenance 6 months later. We suggest that CD4⁺ T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adjuvants, Immunologic - administration & dosage / Adjuvants, Immunologic - pharmacology / Adult / adults / Antibodies / Antibodies, Viral - immunology / Antibody Formation - drug effects / Avian flu / avian influenza / B lymphocytes / Biological Sciences / CD4-positive T-lymphocytes / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - immunology / Cell Proliferation - drug effects / Clinical trials / Dosage / Dose-Response Relationship, Immunologic / emerging diseases / H5N1 subtype influenza A virus / Humans / Immune response / Immunization / Immunogenicity / immunologic memory / Immunologic Memory - drug effects / Influenza A virus / Influenza A Virus, H5N1 Subtype - drug effects / Influenza A Virus, H5N1 Subtype - immunology / Influenza Vaccines - administration & dosage / Influenza Vaccines - immunology / Influenza Vaccines - pharmacology / interferon-gamma / Lymphocytes / Memory / Neutralization Tests / neutralizing antibodies / P values / Phenotype / Polysorbates - administration & dosage / Polysorbates - pharmacology / Proteins / Secondary immunization / Squalene - administration & dosage / Squalene - pharmacology / subunit vaccines / T cell receptors / T lymphocytes / Th1 Cells - cytology / Th1 Cells - drug effects / Th1 Cells - immunology / Time Factors / Vaccination / Vaccines