CD4+T‐cell immunity after pandemic influenza vaccination cross‐reacts with seasonal antigens and functionally differs from active influenza infection

• DOI: 10.1002/eji.201242393
• Publication Date: 2012-05-14T12:52:01Z
• Authors: Tina Schmidt; Jan Dirks; Martin Enders; Barbara C. Gärtner; Heike Uhlmann‐Sch...; Urban Sester; Martina Sester
• Keywords: Adult; CD4-Positive T-Lymphocytes; Immunity, Cellular; 0303 health sciences; Enzyme-Linked Immunosorbent Assay; Cross Reactions; Middle Aged; Antibodies, Viral; Flow Cytometry; Statistics, Nonparametric; 3. Good health; Interferon-gamma; 03 medical and health sciences; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Neutralization Tests; Influenza, Human; Humans; Interleukin-2; Pandemics

Antigen‐specific antibodies are well characterized after vaccination with pandemic H1N1 or seasonal influenza vaccines. However, knowledge on cellular immunity toward pandemic H1N1 after vaccination and infection and cross‐reactivities toward seasonal antigens is limited. Nineteen individuals were vaccinated with the pandemic H1N1 vaccine. Among those, ten had been prevaccinated against seasonal influenza. CD4+ T cells specific for pandemic H1N1 and for seasonal vaccine, and antibodies were monitored using flow cytometry and ELISA/neutralization assays, respectively. In addition, seven patients with acute pandemic influenza infection were analyzed. Pandemic H1N1 vaccination induced a strong 4.63‐fold (IQR 4.16) increase in antigen‐specific CD4+ T cells that was more pronounced in individuals not prevaccinated with seasonal influenza (p = 0.01). T‐cell levels toward seasonal vaccine concomitantly rose by 2.71‐fold (IQR 2.26). Likewise, prevaccination with seasonal influenza induced a less pronounced increase in specific antibodies. Influenza‐specific T cells in vaccinees had a Th1 phenotype mainly coexpressing IFN‐γ and IL‐2, whereas patients with active pandemic influenza showed a shift toward cells predominantly expressing IFN‐γ. In conclusion, T cells toward seasonal influenza antigens cross‐react with pandemic H1N1 antigens and affect induction of specific T cells after pandemic influenza vaccination. In addition, the cytokine patterns of specific T cells during acute H1N1 infection and after vaccination differ, and the predominantly dual‐positive cytokine profile of vaccine‐induced T cells suggests sufficient functionality to confer successful virus control.