Evaluation of Immune Responses to Seasonal Influenza Vaccination in Healthy Volunteers and in Patients After Stem Cell Transplantation

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Abstract
Influenza causes significant morbidity and mortality in immunocompromised stem cell transplantation (SCT) recipients. Measurement of cellular and humoral immunological responses might increase our understanding of how to estimate a protective response to influenza vaccination. Eighteen healthy subjects and 14 SCT patients tested before and 4 weeks after influenza vaccination were included in the study. Peripheral blood lymphocytes were stimulated with influenza peptides and Enzyme-Linked ImmunoSpot assays to measure the production of intracellular interferon-γ, interleukin-4 and interleukin-13. Prelabeled major histocompatibility complex class I pentamers were used for the detection of influenza-specific CD8+ T-cells. B-cell Enzyme-Linked ImmunoSpot and hemagglutination inhibition assays were performed to enumerate influenza-specific antibody-secreting cells and titer of neutralizing antibodies. Influenza vaccination elicited strong cell-mediated immune responses in the healthy controls (P≤0.003 for all four peptides) and SCT patients (P≤0.008). The percentage of CD8+ specific cells increased significantly after vaccination both in volunteers (P=0.005) and in patients (P≤0.003). The number of influenza-specific antibody-secreting cells increased after vaccination both in volunteers (P=0.009) and in patients (P=0.01). Twenty-nine percent of SCT patients demonstrated protective antibody levels to influenza A H1/N1 serotype. Seasonal vaccination against influenza boosts the cellular immune response both in SCT patients and healthy controls. The protective effect is lower in the patients in general and especially on those, vaccinated early after SCT.