Safety and immunogenicity profile of an experimental hepatitis B vaccine adjuvanted with AS04

Boland, Greet J.; Beran, Jiřı́; Lievens, M.; Sasadeusz, Jose; Dentico, P; Nothdurft, Hans Dieter; Zuckerman, JN; Genton, Blaise; Steffen, Robert; Loutan, Louis; Hattum, Jan van; Stoffel, M.

doi:10.1016/j.vaccine.2004.06.006

Cited by 85 publications

(48 citation statements)

References 8 publications

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“…21 Similarly, in adult patients with cholestatic liver disease, a significantly better response to vaccination was seen as compared to noncholestatic forms of liver disease (43% vs. 7%). 22 The better immunogenicity of the adjuvanted HB-AS04 vaccine observed in this study confirms previous results in healthy subjects 16,17 as well as in prehemodialysis and hemodialysis patients. 23 Long-term protection after the HB-AS04 booster dose has not been evaluated in this study.…”

Section: Discussionsupporting

confidence: 90%

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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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Section: Discussionsupporting

confidence: 90%

“…The adjuvant system 04 containing aluminium and monophosphoryl lipid A (MPL ® , Corixa, Seattle, WA), has been shown to improve the immune response to HBsAg and to be well tolerated in healthy subjects. 16,17 The HB-AS04 vaccine might thus confer improved protection against HB in pre-liver transplant patients.…”

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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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“…7 After the first and second dose of ASO4, substantially more subjects were seropositive for anti-HBV antibodies than after the first and third dose of aluminum adjuvanted vaccine (Table 1). Thus, the ASO4 adjuvant provided the potential for an effective two dose HBV vaccine schedule.…”

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confidence: 99%

“…No serious adverse events (SAEs) related to the vaccinations occurred, and the overall incidence of vaccine-related adverse events (AEs) (e.g., pain, redness and swelling around the injection site) was comparable between groups. 7 For patients undergoing haemodialysis, the Centers for Disease Control recommends stronger or increased doses of HBV vaccine to assure protective immunity. 8 A clinical trial comparing the immune responses of pre-haemodialysis and haemodialysis patients showed four doses of HBV vaccine was more effective with ASO4 adjuvant than with aluminum adjuvant (Table 1).…”

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Improving vaccine delivery using novel adjuvant systems

Pichichero¹

2008

Human Vaccines

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ASO4, a novel adjuvant, contains aluminum hydroxide and monophosphoryl lipid (MPL) (500 mg aluminum hydroxide and 50 mg 3-O-desacyl-4' MPL A). Aluminum hydroxide is an adjuvant known to facilitate vaccine antigen delivery and transport to the draining lymph nodes by creating a 'depot' at the injection site. 2 Like all aluminum adjuvants, aluminum hydroxide helps improve immunogenicity of low molecular weight antigens, which could otherwise clear rapidly from the injection site or draining lymph nodes. 2 MPL, a non-toxic derivative of lipopolysaccharide, improves specific antibody and cell-mediated immune responses to vaccination. 4 With only minimal toxicity, 5 MPL enhances macrophage and B-and Tcell responses, as well as T-helper cell generation. 5,6 AS04 adjuvant has been shown to improve vaccine-induced immune responses in hepatitis B (HBV) and cervical cancer vaccines.In 2004, Boland et al. 7 described a randomized study where healthy subjects received two doses of HBV vaccine with ASO4 adjuvant or three doses of HBV vaccine with aluminum adjuvant. 7 After the first and second dose of ASO4, substantially more subjects were seropositive for anti-HBV antibodies than after the first and third dose of aluminum adjuvanted vaccine (Table 1). Thus, the ASO4 adjuvant provided the potential for an effective two dose HBV vaccine schedule. In addition, after two doses of ASO4 adjuvanted vaccine, geometric mean titers (GMT) were two times higher than those observed with the aluminum adjuvanted vaccine (7,832 mlU/ml vs 3,725 mlU/ml). No serious adverse events (SAEs) related to the vaccinations occurred, and the overall incidence of vaccine-related adverse events (AEs) (e.g., pain, redness and swelling around the injection site) was comparable between groups. 7 For patients undergoing haemodialysis, the Centers for Disease Control recommends stronger or increased doses of HBV vaccine to assure protective immunity. 8 A clinical trial comparing the immune responses of pre-haemodialysis and haemodialysis patients showed four doses of HBV vaccine was more effective with ASO4 adjuvant than with aluminum adjuvant (Table 1). 9 More patients achieved seroprotection at three months (p = 0.005) and remained seroprotected at 36 months with ASO4 adjuvanted vaccine than with aluminum adjuvanted vaccine (p = 0.03, Table 1). 9 At three and seven months post final dose, signficiantly more patients in the HBV-ASO4 adjuvant group had anti-HB concentrations >100 mlU/mL (p < 0.001 and p < 0.04, respectively), and a higher percentage retained these high anti-HB levels at 36 months

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“…TLR-dependent adjuvants act directly on dendritic cells (DCs), inducing the up-regulation of cytokines, MHC class II, and costimulatory molecules, and promoting DC migration to the T cell area of the lymph node (1,6). One example of TLR-dependent adjuvant is represented by nonmethylated CpG oligonucleotide (CpG), used as vaccine adjuvant in both preclinical and clinical studies (7,8). CpG acts through TLR9, expressed by human plasmacytoid DCs and B cells (9).…”

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confidence: 99%

Molecular and cellular signatures of human vaccine adjuvants

Mosca

Tritto

Muzzi

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

430

335

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Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b؉ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.innate immunity ͉ microarray ͉ MF59 ͉ alum ͉ CpG ͉ oligonucleotide

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Safety and immunogenicity profile of an experimental hepatitis B vaccine adjuvanted with AS04

Cited by 85 publications

References 8 publications

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

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

Improving vaccine delivery using novel adjuvant systems

Molecular and cellular signatures of human vaccine adjuvants

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