The immunogenicity and reactogenicity profile of a candidate hepatitis B vaccine in an adult vaccine non-responder population

Jacques, P. J.; Moens, Guido; Desombere, Isabelle; Dewijngaert, J; Leroux‐Roels, Geert; Wettendorff, Martine; Thoelen, S

doi:10.1016/s0264-410x(02)00397-3

Cited by 84 publications

(65 citation statements)

References 15 publications

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“…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. 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.…”

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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“…18 A high-antigen-content vaccine with a novel adjuvant (MPL plus alum; AS04) is also associated with higher seroprotective rates and geometric mean antibody levels in nonresponders. 12,18 Other novel vaccines, including a triple-antigen HBsAg vaccine (S, pre-S1, pre-S2) 13,17 and a DNA vaccine, 16 have demonstrated improved efficacy in nonresponders. Multisite revaccination with HBsAg-Eng vaccine via the intradermal route can also induce seroconversion in some nonresponders.…”

Section: Demographics and Participant Dispositionmentioning

confidence: 99%

Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine

Halperin

Ward

Dionne³

et al. 2013

Human Vaccines & Immunotherapeutics

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“…9 ASO4 adjuvant was also assessed in an adult population who were non-responsive to a licensed HBV vaccine (antibody hepatitis B titers <10 mlU/ml, Table 1). 11 After failing to respond to a four-dose HBV vaccine regimen, subjects received three additional doses of HBV vaccine with ASO4 adjuvant or aluminum adjuvant. 11 One month after the first dose, significantly more patients achieved seroprotection with the ASO4 adjuvanted vaccine than with the aluminum adjuvanted vaccine (p = 0.03), and more subjects remained seroprotected one month after the third dose (p < 0.001) ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…11 After failing to respond to a four-dose HBV vaccine regimen, subjects received three additional doses of HBV vaccine with ASO4 adjuvant or aluminum adjuvant. 11 One month after the first dose, significantly more patients achieved seroprotection with the ASO4 adjuvanted vaccine than with the aluminum adjuvanted vaccine (p = 0.03), and more subjects remained seroprotected one month after the third dose (p < 0.001) ( Table 1). GMTs after the final vaccine dose reached 1,937 mlU/ml in the ASO4 adjuvant group compared with 111 mlU/ml in the aluminum adjuvant group (p = 0.0001).…”

Section: Introductionmentioning

confidence: 99%

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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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The immunogenicity and reactogenicity profile of a candidate hepatitis B vaccine in an adult vaccine non-responder population

Cited by 84 publications

References 15 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

Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine

Improving vaccine delivery using novel adjuvant systems

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