A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients

Abstract

Prehemodialysis and hemodialysis patients are at an increased risk of hepatitis B infection and have an impaired immune response to hepatitis B vaccines. We evaluated the immune response to the new adjuvant of hepatitis B vaccine AS04 (HBV-AS04) in this population. We measured antibody persistence for up to 42 months, and the anamnestic response and safety of booster doses in patients who were no longer seroprotected. The primary vaccination study showed that HBV-AS04 elicited an earlier antibody response and higher antibody titers than four double doses of standard hepatitis B vaccine. Seroprotection rates were significantly higher in HBV-AS04 recipients throughout the study. The decline in seroprotection over time was significantly less in the HBV-AS04 group with significantly fewer primed patients requiring a booster dose over the follow-up period. Solicited/unsolicited adverse events were rare following booster administration. Fifty-seven patients experienced a serious adverse event during the follow-up; none of which was vaccine related. When HBV-AS04 was used as the priming immunogen, the need for a booster dose occurred at a longer time compared to double doses of standard hepatitis B vaccine. Hence, in this population, the HBV-AS04 was immunogenic, safe, and well-tolerated both as a booster dose after HBV-AS04 or standard hepatitis B vaccine priming.

Designing Vaccines against Human Papillomavirus and Hepatitis B Virus: Similarities and Differences for Preventable Viral Infections and role of AS04 Adjuvant System in Addressing Specific Challenges

“…Similarly, at Month 42 about 78% of the subjects in the AS04-adjuvanted HBV vaccine group were still seroprotected against HBV as compared with 52% in the control group. These long term follow up data are consistent with the observation that pre-heamodialysis and haemodialysis patients loose more rapidly seroprotective levels of anti-HBs [147]. Therefore anti-HBs antibody concentrations have to be followed up regularly and most subjects need repeated booster doses of the vaccine.…”

“…The decrease in seroprotection rate over time was significantly slower in the AS04-adjuvanted HBV vaccine group, and a booster dose was required less rapidly than in the standard HBV vaccine group. Indeed, fewer patients primed with AS04-adjuvanted HBV vaccine had to receive a booster dose during the follow-up period (16.7% versus 42.9 in control group; p=0.0098) [147].…”

“…The decrease in seroprotection rate over time was significantly slower in the AS04-adjuvanted HBV vaccine group, and a booster dose was required less rapidly than in the standard HBV vaccine group. Indeed, fewer patients primed with AS04-adjuvanted HBV vaccine had to receive a booster dose during the follow-up period (16.7% versus 42.9 in control group; p=0.0098) [147].The aim for both AS04-adjuvanted vaccines is to elicit an enhanced immune response with a long duration for their specific population. The benefits of the AS04 Adjuvant System for both vaccines are summarised in Table 4.…”

Vaccination contre l’hépatite B

“…En effet, ce vaccin qui est administré en présence d'alun comme adjuvant, [19,20]. Plusieurs solutions ont été envisagées pour améliorer la réponse au vaccin chez les mauvais répondeurs : l'utilisation d'adjuvants plus puissants [21], la voie d'injection intradermale à la place de l'intramusculaire classiquement utilisée [22], et l'utilisation de vaccins contenant, en plus de la petite protéine virale, les protéines d'enveloppe moyenne et grande du virus. Ces vaccins, également appelés vaccins de troisième génération, ont fait leurs preuves en améliorant la réponse chez des individus mauvais répondeurs [23].…”

Safety and immunogenicity of an investigational adjuvanted hepatitis B vaccine (HB-AS02V) in healthy adults

“…Results of clinical studies show HB-AS04 to elicit higher and more persistent levels of anti-HBs antibodies than double doses of a conventional recombinant HBV vaccine. [24][25][26][27] The non-aluminum based AS02 adjuvant system combines MPL and QS21 in an oil-in-water emulsion with synergistic immunostimulant properties. 8 The AS02 adjuvant system has previously been shown to elicit stronger and more persistent antibody responses against HBsAg both in healthy adult volunteers and in patients with renal insufficiency than adjuvant systems containing MPL alone.…”