Immunogenicity and safety of an experimental adjuvanted hepatitis B candidate vaccine in liver transplant patients

Abstract

Patients with chronic liver disease are at higher risk of hepatitis B (HB) virus infection before and after liver transplantation, and they commonly have a suboptimal immune response to HB vaccines. In this randomized trial, we compared the immunogenicity of primary vaccination with 2 doses of an experimental adjuvanted HB vaccine (adjuvant system 04 containing aluminium and monophosphoryl lipid A [HB-AS04] ) to that of 3 double doses of a licensed HB vaccine in 93 liver transplant candidates. Depending on the waiting list for liver transplantation, a booster dose of HB-AS04 or double booster dose of the licensed HB vaccine was given before or after surgery, at 6 to 12 months after initiation of the vaccination course. The percentage of subjects with seroprotective anti-HB surface antibody concentrations 1 month after booster was twice as high in the HB-AS04 group (60.0%), vs. patients in the comparator group (32.0%) (P ϭ 0.035). In subjects who did not undergo liver transplantation before administration of the booster, better immunogenicity results were obtained: 80% of subjects were seroprotected after HB-AS04 vaccination vs. 60% with the comparator (P ϭ 0.2302). Despite a slightly higher reactogenicity, the safety profile of the HB-AS04 vaccine was clinically acceptable. In conclusion, an improved antibody response was observed in liver transplant candidates with 3 doses of HB-AS04, as compared to 4 double doses of a comparator. Liver transplant candidates could benefit from the use of this experimental adjuvanted HB vaccine to further increase their protection against HB infection. Patients undergoing liver transplantation have an increased risk of exposure to hepatitis B (HB) virus, mainly due to transmission of the virus from the donor organ and, to a lesser extent, due to multiple transfusions of blood products. [1][2][3][4] To protect these patients against de novo HB infection acquired during or after Abbreviations: HB, hepatitis B; HBsAg, hepatitis B surface antigen; anti-HBs, antibody to hepatitis B surface antigen; AS04, adjuvant system 04 containing aluminium and monophosphoryl lipid A; GMC, geometric mean concentration; SAE, serious adverse event.

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

“…84 The AS02 and AS04 adjuvant system, which consists of monophosphoryl lipid A adsorbed on either aluminum or oil, has been evaluated in prophylactic vaccines against HBV. 85 The AS04-adjuvant HBV vaccine (Fendrix) boosted the anti-HBs antibody response with an acceptable safety profile not only in liver-transplant candidates, 86 who had a suboptimal response to double doses of recombinant hepatitis B vaccine, 87 but also in healthy non-responder individuals. 88 The AS02-adjuvant HBV vaccine (Supervax) induced more rapid, enhanced, and persistent protection with fewer doses than the currently-licensed AS04-adjuvant HBV vaccine.…”

Recombinant Hepatitis B Vaccine Adjuvanted With AS04 in Dialysis Patients: A Prospective Cohort Study

“…Preliminary data exist on adjuvanted HBV-AS04 use among liver transplant candidates [20] and HIV-infected patients [21,22]. Previous evidence has shown a high immunogenicity profile of adjuvanted HB-AS04 among healthy individuals [23].…”

Old and new adjuvants for hepatitis B vaccines

“…An improved anti-HBs response was observed in these patients with three doses of AS04-adjuvanted vaccine as compared to four double doses of Engerix-B [34]. Liver transplant candidates could thus benefit from the superior immunogenicity of this vaccine and be better protected against HBV infection.…”

“…The immunogenicity and safety of AS04-adjuvanted hepatitis B vaccine have also been examined in patients with end-stage liver disease on the waiting list for liver transplantation [34]. An improved anti-HBs response was observed in these patients with three doses of AS04-adjuvanted vaccine as compared to four double doses of Engerix-B [34].…”