Immunization with an adjuvant hepatitis B vaccine after liver transplantation for hepatitis B–related disease

Abstract

Patients who undergo transplantation for hepatitis B virus (HBV)-related diseases are treated indefinitely with hepatitis B hyperimmunoglobulin (HBIG) to prevent endogenous HBV reinfection of the graft. Active immunization with standard hepatitis B vaccines in these patients has recently been reported with conflicting results. Two groups of 10 liver transplant recipients on continuous HBIG substitution who were hepatitis B surface antigen (HBsAg) positive and HBV DNA negative before transplantation were immunized in a phase I study with different concentrations of hepatitis B s antigen formulated with the new adjuvants 3-deacylated monophosphoryl lipid A (MPL) and Quillaja saponaria (QS21) (group I/vaccine A: 20 microg HBsAg, 50 microg MPL, 50 microg QS21; group II/vaccine B: 100 microg HBsAg, 100 microg MPL, 100 microg QS21). Participants remained on HBIG prophylaxis and were vaccinated at weeks 0, 2, 4, 16, and 18. They received 3 additional doses of vaccine B at bimonthly intervals if they did not reach an antibody titer against hepatitis B surface antigen (anti-HBs) greater than 500 IU/L. Sixteen (8 in each group) of 20 patients (80%) responded (group I: median, 7,293 IU/L; range, 721-45,811 IU/L anti-HBs; group II: median, 44,549 IU/L; range, 900-83,121 IU/L anti-HBs) and discontinued HBIG. They were followed up for a median of 13.5 months (range, 6-22 months). The vaccine was well tolerated. In conclusion, most patients immunized with the new vaccine can stop HBIG immunoprophylaxis for a substantial, yet to be determined period of time.

Therapeutic vaccination of a liver transplant recipient suffering from fulminant hepatitis B during pregnancy

“…Vaccination with a recombinant HBV vaccine formulated with monophosphoryl lipid A and Quillaja saponaria (QS-21) has been most promising. 1 However, no effective vaccine for the immunization of liver transplant recipients with nonresponder characteristics is available so far. Further studies are necessary to assess whether the encouraging results with Sci-B-Vac can be reproduced in a larger cohort of liver transplant recipients.…”

Viral Infection in the Renal Transplant Recipient

“…Alternative vaccination strategies have been studied. Twenty liver transplant patients given extra doses of hepatitis B vaccine with one of two new adjuvants demonstrated a serologic response rate of 80% (180). Twenty-four renal transplant recipients who did not respond to intramuscular vaccine had an overall response rate of 63% to a series of eight intradermal vaccinations followed by an intramuscular vaccination (181).…”

Elimination of Immunodominant Epitopes from Multispecific DNA-Based Vaccines Allows Induction of CD8 T Cells That Have a Striking Antiviral Potential

“…Although many experimental, therapeutic HBV vaccines have been developed (17)(18)(19)(20)(21), these have failed so far to reproducibly clear chronic HBV infection. The major problem for therapeutic HBV vaccines is the delivery of Ags into the tolerogen milieu of chronically infected patients.…”