Long-term immunogenicity after yellow fever vaccination in immunosuppressed and healthy individuals.

BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.

17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients.

BACKGROUND: The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. MATERIALS AND METHODS: Fifteen patients using different immunosuppressive drugs and 30 healthy individuals vaccinated 0-22 years ago were included. The serological response was measured using the plaque reduction neutralization test (PRNT). CD8(+) and CD4(+) T-cell responses were measured following proliferation and re-stimulation with YFV peptide pools. Phenotypic characteristics and cytokine responses of CD8(+) T-cells were determined using class I tetramers. RESULTS: The geometric mean titre of neutralizing antibodies was not different between the groups (p = 0.77). The presence of YFV-specific CD4(+) and CD8(+) T-cell did not differ between patients and healthy individuals (15/15, 100.0% vs. 29/30, 96.7%, p = 0.475). Time since vaccination correlated negatively with the number of YFV-specific CD8(+) T-cells (r = -0.66, p = 0.0045). Percentages of early-differentiated memory cells increased (r = 0.67, p = 0.017) over time. CONCLUSION: These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains.