In 2007, a 55-year old Caucasian male kidney transplant (KTX) patient received live attenuated YFV-17D vaccine (YF-VAX®
, Sanofi–Pasteur), in addition to concurrent immunization with an inactivated hepatitis A vaccine in preparation for a trip to South America. At the time of vaccination, the subject was 19 years post deceased donor kidney transplant and receiving maintenance immune suppression with cyclosporine (100 mg, twice daily) and mycophenolic acid (360 mg, twice daily). Shortly after immunization, the patient reviewed the vaccine contraindications and realizing the risks associated with his vaccination, he contacted his nephrologist who then contacted OHSU Transplant Infectious Disease for further consultation. Since viremia could not be monitored in real-time, liver enzymes were followed as a marker for yellow fever associated viscerotropic disease (YEL-AVD), a potentially life threatening condition that results in virus dissemination and multi-organ failure (4
). Prior to vaccination, the subject had average AST values of 28 U/mL (range = 19–38) and ALT levels of 27 U/mL (range = 16–27) (). By 11 days post-vaccination, the patient did not report having a fever but AST and ALT levels had increased to 60 U/mL and 53 U/mL, respectively. IVIG was administered on days 20, 21 and 22 post-immunization, with a daily dose of 500 mg/kg. AST and ALT levels had returned to normal by day 18 post-vaccination but total bilirubin was elevated (2.4 Units/mL) at day 25 post-vaccination. On day 26 (i.e., four days following final IVIG administration), the patient reported what may have been an urticarial or eczematous response on his face that resolved within five days. Total bilirubin, AST, and ALT levels were within normal range when examined at day 47 post-vaccination. Follow-up with the patient at approximately eight months post-vaccination indicated no long-term adverse events.
Analysis of liver enzymes and immune responses following yellow fever vaccination of a kidney transplant patient (KTX)
Retrospective testing was performed on patient blood samples and on the IVIG lot administered to the KTX patient. The IVIG lot yielded a YFV-specific 50% plaque reduction neutralizing test (PRNT50) value of 320, demonstrating the presence of YFV-specific neutralizing antibodies similar to ten other lots of IVIG sampled across four vendors (geometric mean PRNT50 = 226, range = 80–320). Blood samples were drawn from the patient at 20, 47, and 246 days after vaccination and analyzed for YFV-specific neutralizing antibody as well as CD4+ and CD8+ T cell responses (). For comparison, the immune responses of eight healthy adults at 30 days post-YFV-17D vaccination were examined. The patient seroconverted by 20 days post-vaccination with antibody titers within the lower range of the controls. In contrast to neutralizing antibody levels, the patient’s virus-specific CD4+ and CD8+ T cell responses remained below detection (i.e., equivalent to naïve controls) at all time points examined.