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

Influenza causes significant morbidity and mortality in immunocompromised stem cell transplant (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 four influenza peptides; three based on sequences from the hemagglutinin and one from the M1 protein. Elispot assays were performed to measure the production of intracellular interferon-gamma (IFN-) and interleukin-13 (IL-13). Pre-labeled MHC class I pentamers were used for the detection of influenza-specific CD8+ T-cells. B-cell Elispot was performed to enumerate influenza-specific antibody-secreting cells (ASCs). Finally, haemagglutination inhibition (HIA) was used to determine the serum titers of neutralizing antibodies. Influenza vaccination elicited strong cell-mediated immune responses in the healthy volunteers (p≤0.003 for all four peptides) and SCT patients (p≤0.008). The percentage of CD8+ influenza-specific cells increased significantly after vaccination of both volunteers (p=0.005) and patients (p≤0.003). The number of influenza-specific ASCs increased as well (in volunteers p=0.009, in patients p=0.01). Only 29% of the SCT patients developed protective antibody levels to the influenza A H1/N1 serotype while no patient had protective antibody levels to H3/N2 or influenza B types. All responses were lower in patients studied less than 6 months after SCT compared to those studied later after SCT. These results indicate that seasonal vaccination against influenza can boost the cellular immune response in SCT patients and healthy controls, while B-cell responses are suboptimal in SCT patients.