Efficacy and safety of an intravenous monoclonal anti‐HBs in chronic hepatitis B patients

Nunen, A.B. van; Baumann, Matthias; Manns, Michael P.; Reichen, Jürg; Spengler, Ulrich; Marschner, Jens-Peter; Man, Robert A. de

doi:10.1034/j.1600-0676.2001.021003207.x

Cited by 19 publications

(12 citation statements)

References 16 publications

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“…The near identity of clones of HBV bNAbs in unrelated elite individuals is akin to reports for elite responders to HIV-1 (Scheid et al, 2011; West et al, 2012), influenza (Laursen and Wilson, 2013; Pappas et al, 2014; Wrammert et al, 2011), Zika (Robbiani et al, 2017), and malaria (Tan et al, 2018). However, none of the elite anti-HBs bNAbs shares both IgH and IgL with previously reported HBV neutralizing antibodies, the best of which have been tested in the clinic but are less potent than some of the bNAbs reported here (libivirumab IC 50 : 35 ng/ml, tuvirumab IC 50 : ~100 ng/ml) (Galun et al, 2002; Heijtink et al, 2001; van Nunen et al, 2001).…”

Section: Discussioncontrasting

confidence: 53%

Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

Wang

Michailidis

et al. 2020

Preprint

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SUMMARYAlthough there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and constitute clinical correlates of recovery from infection. To examine the human neutralizing antibody response to HBV in elite neutralizers we screened 144 individuals. The top individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection, but selected for resistance mutations in mice with established infection. In contrast, infection was controlled by a combination of bNAbs targeting non-overlapping epitopes with complementary sensitivity to mutations that commonly emerge during human infection. The co-crystal structure of one of the bNAbs with a peptide epitope containing residues frequently mutated in human immune escape variants revealed a loop anchored by oppositely charged residues. The structure provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.

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Section: Discussioncontrasting

confidence: 53%

Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

Wang

Michailidis

et al. 2020

Preprint

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“…The success of HBIG in these conditions raises the possibility of antibody-mediated immunotherapy against chronic HBV infection (25). Indeed, three pioneering studies tested the efficacy of anti-HBs monoclonal antibodies or HBIG in CHB patients, alone or in combination with alpha-interferon (44–46). All these studies demonstrated the temporary reduction of HBsAg and HBV DNA after a high dose of anti-HBs antibody treatment, though the long-term clearance of HBsAg was not observed.…”

Section: The Efficacy Of Antibody-medicated Immunotherapy or Triggerimentioning

confidence: 99%

“…The efficacy of specific antibody mediated reduction of HBsAg has been described in a previous section of this review. It is shown that using HBIG or monoclonal antibodies against HBsAg can efficiently decrease the serum level of HBsAg in CHB patients (44–47). In addition, high affinity human anti-HBs and anti-Pre-S1-monoclonal antibodies have been developed recently, and these antibodies have shown an excellent ability to efficiently clear circulating HBsAg in different mouse models (103–106).…”

Section: How To Optimize the Therapeutic Efficacy Of Strategies Targementioning

confidence: 99%

Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response

Zhang

Shicheng

et al. 2019

Front. Immunol.

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The central role of the cellular immune response in the control and clearance of the hepatitis B virus (HBV) infection has been well-established. The contribution of humoral immunity, including B cell and antibody responses against HBV, has been investigated for a long time but has attracted increasing attention again in recent years. The anti-HBs antibody was first recognized as a marker of protective immunity after the acute resolution of the HBV infection (or vaccination) and is now defined as a biomarker for the functional cure of chronic hepatitis B (CHB). In this way, therapies targeting HBV-specific B cells and the induction of an anti-HBs antibody response are essential elements of a rational strategy to terminate chronic HBV infection. However, a high load of HBsAg in the blood, which has been proposed to induce antigen-specific immune tolerance, represents a major obstacle to curing CHB. Long-term antiviral treatment by nucleoside analogs, by targeting viral translation by siRNA, by inhibiting HBsAg release via nucleic acid polymers, or by neutralizing HBsAg via specific antibodies could potentially reduce the HBsAg load in CHB patients. A combined strategy including a reduction of the HBsAg load via the above treatments and the therapeutic targeting of B cells by vaccination may induce the appearance of anti-HBs antibodies and lead to a functional cure of CHB.

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“…Notably, a murine anti-HBs mAb was employed to treat hypogammaglobulinemic HBV-infected individuals yielding reduced HBV DNA levels (44). Moreover, a human anti-HBs mAb, alone or in combination with interferon-α, was used in patients with chronic HBV infection, resulting in a substantial decrease in HBsAg titers (45). Interestingly, combination therapy with interferon-α successfully cleared HBsAg.…”

Section: Perspective For a Combined Use Of Humabs And Nucleos(t)ide Amentioning

confidence: 99%

Human Monoclonal Antibodies as Adjuvant Treatment of Chronic Hepatitis B Virus Infection

et al. 2019

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Despite the availability of an effective prophylactic vaccine leading to sterilizing immunity, hepatitis B virus (HBV) is responsible for chronic liver disease in more than 250 million individuals, potentially leading to cirrhosis and hepatocellular carcinoma. Antiviral drugs able to completely suppress virus replication are indeed available but they are, by and large, unable to eradicate the virus. Several alternative new treatment approaches are currently being developed but none have so far captured the interest of clinicians for possible clinical development. A constant feature of chronic HBV infection is T-cell exhaustion resulting from persistent exposure to high antigen concentrations as shown by the high expression of programmed cell death protein 1 (PD-1) by HBV-specific CD8 T cells. One way of tackling this problem is to develop HBV-specific neutralizing antibodies that would clear excess envelope proteins from the circulation, allowing for nucleos(t)ide analogs or other antiviral drugs now in preclinical and early clinical development to take advantage of a reconstituted adaptive immunity. Several fully human monoclonal antibodies (mAb) have been developed from HBV-vaccinated and subjects convalescent from acute hepatitis B that show different properties and specificities. It is envisaged that such neutralizing mAb may be used as adjuvant treatment to reduce viral protein load, thus rescuing adaptive immunity in an effort to optimize the effect of antiviral drugs.

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Efficacy and safety of an intravenous monoclonal anti‐HBs in chronic hepatitis B patients

Cited by 19 publications

References 16 publications

Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response

Human Monoclonal Antibodies as Adjuvant Treatment of Chronic Hepatitis B Virus Infection

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