Pandemic influenza vaccination elicits influenza-specific CD4+ Th1-cell responses in hypogammaglobulinaemic patients: four case reports.

In these case reports, we investigated pandemic influenza 2009 vaccination of primary hypogammaglobulinaemic patients. Three combined variable immunodeficiency (CVID) patients and one X-linked agammaglobulinaemia (XLA) patient were vaccinated with the pandemic vaccine A/California/7/2009 (H1N1)-like split virus (X179a) adjuvanted with the oil-in-water emulsion AS03. Subsequently, serum and peripheral blood mononuclear cells were sampled and used to measure the haemagglutination inhibition (HI) and antibody-secreting cell (ASC) responses. In addition, the IFN-γ, IL-2 and TNF-α producing CD4(+) Th1-cell response was determined as these cytokines are important indicators of cell-mediated immunity. Two of the CVID patients responded to vaccination as determined by a >4-fold rise in HI antibodies. These subjects also had influenza-specific ASC numbers, which, albeit low, were higher than prevaccination levels. In addition, vaccination induced CD4(+) Th1-cell responses in both the XLA patient and the CVID patients, although the frequency of influenza-responsive cells varied amongst the patients. These results suggest that hypogammaglobulinaemia patients can mount a CD4(+) Th1 cell-mediated response to influenza vaccination and, additionally, that influenza vaccination of some hypogammaglobulinaemia patients can produce an influenza-specific humoral immune response. The findings should be confirmed in larger clinical studies.