Rapid, enhanced, and persistent protection of patients with renal insufficiency by AS02V-adjuvanted hepatitis B vaccine

Abstract

The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02 with that of HB-AS04. In this phase III, open, randomized study, 151 hepatitis B vaccine-naïve pre-dialysis, peritoneal dialysis, and hemodialysis patients aged 15 years and older received three doses of HB-AS02 at 0, 1, and 6 months. Another 149 similar patients received four doses of HB-AS04 at 0, 1, 2, and 6 months, and all were followed up for 12 months. HB-AS02 elicited more rapid and persistent seroprotection than HB-AS04, with rates of 77 and 39%, respectively, 1 month after the second vaccine dose, and 94 and 79%, respectively, at 12 months. Superiority of HB-AS02 over HB-AS04 in anti-hepatitis B geometric mean concentrations was found at all time points. HB-AS02 was more reactogenic than HB-AS04, but adverse events were mainly transient, of mild to moderate intensity with no reportable vaccine-related serious events. We conclude that a three-dose primary course of HB-AS02 induced more rapid, enhanced, and persistent protection in patients with renal insufficiency than the licensed four-dose primary schedule of HB-AS04. This adjuvanted vaccine affords greater protection with reduced need for booster doses in patients at high risk of hepatitis B infection.

Anti-HBs antibody persistence following primary vaccination with an investigational AS02v-adjuvanted hepatitis B vaccine in patients with renal insufficiency

“…All booster doses were of a conventional recombinant HBV vaccine (Engerix-B TM or HBVAXPRO TM ). As previously detailed, 16 the HB-AS02 vaccine was more reactogenic than HB-AS04. Local and systemic reactions were, however, mainly mild to moderate in intensity, transient in nature and no increase in reactogenicity was observed after successive vaccine doses in either group.…”

“…16 The higher anti-HBs antibody levels induced by the HB-AS02 vaccine following primary vaccination were maintained over the 36 mo of follow-up, with the enhanced protection provided by the HB-AS02 vaccine apparent in all subgroups of subjects studied (pre-dialysis, peritoneal dialysis and hemodialysis patients). The enhanced immunogenicity of the HB-AS02 vaccine appears to reduce the need for booster doses in this population.…”

“…14, 15 We have previously shown a three-dose primary course of HB-AS02 to induce more rapid seroprotection and higher anti-HBs antibody concentrations in patients with renal insufficiency than a fourdose primary course of HB-AS04 (FENDrix TM ; GlaxoSmithKline Biologicals, Rixensart, Belgium), 16 an adjuvanted HBV vaccine licensed in Europe since 2005 for use in this population. 17 This paper reports persistence of immune response up to 36 months (mo) following primary vaccination in the cohort from the previous study.…”

“…17 This paper reports persistence of immune response up to 36 months (mo) following primary vaccination in the cohort from the previous study. 16 This was an open, international, multicenter, Phase III follow-up study undertaken to evaluate the persistence of anti-HBs antibodies in pre-dialysis, hemodialysis or peritoneal dialysis patients randomized 1:1 to receive primary vaccination with HB-AS02 (administered according to a 0, 1 and 6 mo schedule) or HB-AS04 (administered at 0, 1, 2 and 6 mo) in a previously reported open comparative trial. 16 Subjects were required to be seronegative for anti-HBs antibodies, anti-hepatitis B core antigen antibodies and HBsAg and ≥15 years of age at the time of primary vaccination.…”

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

“…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. 89 Two TLR9 agonists of class B CpG-ODNs called CPG7909 and 1018 ISS in combination with recombinant HBsAg have been tested in clinical trials. The addition of CPG 7909 to the conventional HBV vaccine (Engerix-B) resulted in higher anti-HBs antibody titers and an enhanced late affinity maturation process to increase the avidity of anti-HBs antibody.…”