Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease

Arslan, Mehmet; Wiesner, Russell H.; Sievers, Corey; Egan, Kathleen S.; Zein, Nizar N.

doi:10.1053/jlts.2001.23069

Cited by 89 publications

(88 citation statements)

References 25 publications

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“…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.…”

Section: Contribution Of Tlrs To the Control Of Hbv Infection Zy Ma Ementioning

confidence: 99%

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

Zhang

Yang

et al. 2014

Cell Mol Immunol

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It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus (HBV) infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons (IFNs) and pro-inflammatory cytokines. Experimental results from in vitro and in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T-and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

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Section: Contribution Of Tlrs To the Control Of Hbv Infection Zy Ma Ementioning

confidence: 99%

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

Zhang

Yang

et al. 2014

Cell Mol Immunol

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“…1 The immunization regimen was based on the knowledge that HBV vaccination in cirrhotic patients and non-HBV liver transplant recipients results in a low rate of hepatitis B surface antibody (anti-HBs) seroconversion. 2,3 The study included 17 virologically negative (hepatitis B surface antigen [HBsAg] and HBV-DNA negative by polymerase chain reaction on at least two consecutive assays) liver transplant recipients on cyclosporine monotherapy, who had undergone transplantation for HBV-related cirrhosis 25 to 85 months previously. Fifteen recipients were men.…”

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confidence: 99%

Vaccination for hepatitis B after transplantation: A realistic goal?

Pruett

2002

Hepatology

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L iver transplantation for hepatitis B has become remarkably successful over the past decade. This success has been predicated upon effective therapy to prevent clinical infection of the transplanted liver by hepatitis B virus (HBV). The cornerstone of therapy to prevent HBV infection in the transplanted liver has been the use of hepatitis B immune globulin (HBIG). With the availability of effective antiviral therapy (especially lamivudine with others soon to be available), the repertoire for HBV containment is increasing. There are significant shortcomings to longterm HBIG and lamivudine, not least of which has been cost and drug resistance. The prospect of inducing active immunity against HBV, without the need for additional treatment for the virus, was examined in the article by Angelico et al. in this issue of HEPATOL-OGY. 1 The immunization regimen was based on the knowledge that HBV vaccination in cirrhotic patients and non-HBV liver transplant recipients results in a low rate of hepatitis B surface antibody (anti-HBs) seroconversion. 2,3 The study included 17 virologically negative (hepatitis B surface antigen [HBsAg] and HBV-DNA negative by polymerase chain reaction on at least two consecutive assays) liver transplant recipients on cyclosporine monotherapy, who had undergone transplantation for HBV-related cirrhosis 25 to 85 months previously. Fifteen recipients were men. All patients were HBV-DNA negative (by hybridization assay) at the time of transplantation and 41% were hepatitis D antibody positive. HBIG monotherapy had been given to all patients on a monthly (typically about 5,000 IU) basis until entry into the study. Four weeks after the last dose of HBIG, the patients were started on lamivudine. The anti-HBs titers were followed until they were less than 10 IU/L, a median of 4.5 months after the last HBIG dose. The first course of vaccination used 40 g (double dose) recombinant HBsAg (Recombivax) given intramuscularly at 0, 1, and 2 months. Early response was defined as an anti-HBs titer greater than 100 IU/L at 3 months. One individual (5.9%) developed an early response with an anti-HBs titer of 687 IU/L at month 3 and one developed an anti-HBs titer of 20 IU/L. The 16 nonresponders were given a second course of vaccination: 10 g of recombinant HBsAg intradermally every 15 days for 3 months (6 doses). No additional patient developed an anti-HBs titer Ͼ100 IU/L, so all 16 were given a third vaccination series exactly the same as the first (40 g intramuscularly monthly for 3 doses). One patient responded at month 10 with an anti-HBs titer of 253 IU/L. In aggregate, 2 of 17 (12%) developed an anti-HBs titer greater than 100 IU/L and 3 more (18%) had a titer greater than 10 IU/L after the 3 vaccination courses. Per protocol, the 15 nonresponders resumed intravenous HBIG. Of two responders, one stopped lamivudine and one continued because the anti-HBs response was not durable. No patient developed HBV reinfection. The response in this series to a commercially available recombinant HBsAg vaccine was ...

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“…11,12 Our results obtained in the comparator group are in line with the 25-40% seroprotection rate observed after administration of an accelerated primary vaccination with double doses of licensed HB vaccine in liver transplant candidates. [8][9][10] At the moment of administration of the booster dose (Month 6-12), significantly more subjects (P ϭ 0.0337) were seroprotected in the HB-AS04 group (32.3%) as compared to the comparator group (10.0%), but GMCs were low and comparable in both groups at that time point.…”

Section: Discussionmentioning

confidence: 99%

“…These results confirm that, ideally, the booster dose should be given before surgery to avoid the subsequent negative effect of immunosuppressive medication. 8,10,18 The relatively low seroprotection rates observed with both vaccines after the primary vaccination course and following a booster dose after liver transplantation are not optimal and clearly a disadvantage in centers where waiting lists are not long. These data therefore support the importance of initiating immunization in all liver disease patients as early as possible in the disease evolution, to improve the protection conferred by vaccination of these individuals.…”

Section: Discussionmentioning

confidence: 99%

“…However, an accelerated schedule with double doses of a currently marketed HB vaccine followed by a booster dose provided seroprotection in only 25-40% of subjects. [8][9][10] The poor antibody response of liver transplant candidates to classical HB vaccines is mainly attributed to impaired immunity associated with end-stage liver disease. 11,12 Vaccination against HB is therefore recommended for these patients as soon as possible after the diagnosis of liver disease has been made, preferably at an early stage when the immune system is still functional.…”

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confidence: 99%

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

et al. 2006

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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.

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Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease

Cited by 89 publications

References 25 publications

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

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

Vaccination for hepatitis B after transplantation: A realistic goal?

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

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