CD154 Expression Is Associated with Neutralizing Antibody Titer Levels Postinfluenza Vaccination in Stem Cell Transplant Patients and Healthy Adults

We undertook a prospective longitudinal study to examine humoral and cellular immune responses to influenza vaccination in hematopoietic cell transplant (HCT) patients and healthy adults. Healthy volunteers and HCT patients had blood samples taken prior to influenza vaccination and 30, 90, and 180 days postvaccination. Serum from pre- and postvaccination time points were tested for influenza A IgG and IgM by ELISA as well as tested for neutralizing antibody (NAb) titers via hemagluttination inhibition assay. Polychromatic flow cytometry was used to examine CD4+ T cells for levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and CD154 (CD40 ligand) expression after stimulation with inactivated flu virus. In healthy subjects, we found a significant increase in Influenza A IgG and IgM levels as well as an increase in NAb titers pre- and postinfluenza vaccination. Notably, NAb titers of most HCT patients did not rise to a protective level postvaccination. CD4+ T cell expression of CD154 and cytokine responses were significantly reduced in HCT recipients compared to healthy adults. A lack of B cell reconstitution and dysfunctional CD4 T cell costimulation (as marked by low CD154 expression) is associated with low NAb levels postvaccination in HCT patients.