Therapeutic vaccination for chronic hepatitis B

Kosinska, Anna D.; Bauer, Tanja; Protzer, Ulrike

doi:10.1016/j.coviro.2017.03.011

Cited by 65 publications

(68 citation statements)

References 54 publications

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“…EBAC of unclarified culture bulk supplemented with Benzonase yielded 45% recovery and 5-fold concentration of adenoviral vectors whose purity compared to that obtained with the classical density gradient ultracentrifugation method [25]. HBcAg self-assembles into icosahedral VLPs which have also promising applications as vaccine platform [85], in particular as therapeutic vaccine for chronic hepatitis B [86]. The recovery yield of HBcAg from heat-treated, unclarified E. coli homogenate was about 50% with a purity (ratio of HBcAg content to total protein content) of c. 0.5 and a purification factor (ratio of HBcAg purity in EBAC eluate to that in the feedstock) of c. 2 [26].…”

Section: Ion-exchange Chromatography (Iec)mentioning

confidence: 92%

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

Junter

Lebrun

2020

Journal of Pharmaceutical Analysis

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Section: Ion-exchange Chromatography (Iec)mentioning

confidence: 92%

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

Junter

Lebrun

2020

Journal of Pharmaceutical Analysis

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“…been explored, 13 such as altering the vaccine antigen composition by using combinations of core, X and polymerase antigens in addition to HBsAg; using a DNA vaccine instead of a protein/peptide vaccine; using vaccine vectors; using altered vaccine adjuvants; and using different TV doses, vaccination frequencies and prime-boost methods.…”

Section: Various Strategies For Stimulating T-cell Responses With Tvsmentioning

confidence: 99%

“…Of the immunotherapy options available, other than interferon‐based therapy, only therapeutic vaccines (TVs) have regulatory approval. Various strategies for stimulating T‐cell responses with TVs have been explored, such as altering the vaccine antigen composition by using combinations of core, X and polymerase antigens in addition to HBsAg; using a DNA vaccine instead of a protein/peptide vaccine; using vaccine vectors; using altered vaccine adjuvants; and using different TV doses, vaccination frequencies and prime‐boost methods. The first clinical study of a HBV TV in 1995 showed promising results with 53% achieving undetectable HBV DNA .…”

Section: Introductionmentioning

confidence: 99%

Therapeutic vaccination for chronic hepatitis B: A systematic review and meta‐analysis

Lim

Agcaoili²,

Souza

et al. 2019

Journal of Viral Hepatitis

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Summary Therapeutic vaccines may be promising treatments for chronic hepatitis B (CHB), but their clinical efficacy and safety are unclear. We conducted a systematic review of the evidence for the efficacy and safety of therapeutic vaccines in CHB patients. We searched PubMed, EMBASE and Google Scholar from 1990 until present and abstracts from EASL, APASL and AASLD from 2012 to 2017 and selected randomized controlled trials of CHB patients, comparing therapeutic vaccines with no treatment or standard of care. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by hepatitis B e antigen (HBeAg) status and the comparator (therapeutic vaccines vs no treatment, or therapeutic vaccines + standard of care vs standard of care). Efficacy outcomes were HBeAg seroconversion, hepatitis B virus DNA reduction and hepatitis B virus surface antigen (HBsAg) loss, measured at the end of treatment or end of follow‐up. Effects were reported as risk differences with 95% confidence intervals using a random effects model. Fifteen studies were included. A wide variety of therapeutic vaccines were tested. For HBeAg clearance at the end of follow‐up, when comparing therapeutic vaccines vs no therapy, RD = 0.01, 95% CI −0.05 to 0.07, and when comparing therapeutic vaccines + standard of care vs standard of care, RD = 0.03, 95% CI −0.03 to 0.09. For HBVDNA reduction at the end of follow‐up, when comparing therapeutic vaccines vs no therapy, RD = −0.03, 95% CI −0.08 to 0.02, and when comparing therapeutic vaccines + standard of care, RD = 0.15, 95% CI 0.02‐0.28. There were only a few studies on HBsAg loss, and hence, the findings were inconclusive. The only efficacy finding was HBVDNA reduction at the end of follow‐up for therapeutic vaccines + standard of care vs standard of care; otherwise, therapeutic vaccines do not appear to be efficacious for the treatment of CHB, but were limited by few RCTs, suboptimal therapeutic vaccines and patient selection.

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“…Spontaneous clearance of HBV through immune-mediated mechanisms, particularly T cell mediated immune responses, in acute and in some chronically infected patients provides a rationale for CHB immunotherapy (9). Ongoing efforts at preclinical and early clinical stages include activation of innate immunity through TLR ligands, treatment with immune checkpoint inhibitors, and/or immunization with HBV antigens delivered by plasmid DNA or viral vectors (7,9). DNA immunization is a safe and reliable method for induction of antibody responses, but this approach requires special delivery such as electroporation, and remains poorly immunogenic for T cells (10).…”

Section: Introductionmentioning

confidence: 99%

“…DNA immunization is a safe and reliable method for induction of antibody responses, but this approach requires special delivery such as electroporation, and remains poorly immunogenic for T cells (10). On the other hand, viral vectors are highly immunogenic and efficient at mounting T cell responses, but their safety remains a concern even for attenuated and replication-deficient viral vectors (9).…”

Section: Introductionmentioning

confidence: 99%

Virus-like vesicles expressing multiple antigens for immunotherapy of chronic hepatitis B

Yarovinsky

Mason

Menon

et al. 2018

Preprint

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Infection with hepatitis B virus (HBV) can initiate chronic hepatitis and liver injury, eventually progressing to liver fibrosis or cancer and causing more than 600,000 deaths each year worldwide. Current treatments for chronic hepatitis B, relying on nucleoside antivirals and interferon, are inadequate and leave an unmet need for immunotherapeutic approaches. This report describes virus-like vesicles (VLV), a form of self-amplifying RNA replicons, which express multiple HBV antigens (polymerase, core, and middle surface) from a single vector (HBV-VLV). The HBV-VLV induces HBV-specific T cell responses to all three HBV antigens. Immunization of naive mice with the multiantigen HBV-VLV renders them resistant to acute challenge with HBV delivered by adeno-associated virus (AAV). Using a chronic model of HBV infection by AAV delivery of HBV, we demonstrate immunotherapeutic potential of the multiantigen HBV-VLV in combination with DNA booster immunization, as 40% of the HBV-VLV-treated mice showed a decline of the serum HBV surface antigen below the detection limit and marked reduction in liver HBV RNA accompanied by induction of HBsAg-specific CD8 T cells. These results warrant further evaluation of multiantigen HBV-VLV for immunotherapy of chronic hepatitis B.IMPORTANCEMore than 240 million people worldwide are chronically infected with hepatitis B virus. Current therapies are not sufficiently effective and are often beyond reach in the developing world. We describe a virus-like vesicle-based immunotherapeutic vaccine that expresses three major antigens of hepatitis B virus as a self-amplifying RNA replicon. By incorporating three HBV antigens in a single vaccine, we ensure broad T cell responses. We demonstrate that immunization with this vaccine protects mice from hepatitis B virus in a model of acute challenge. Importantly, treatment with this vaccine shows 40% efficacy in a mouse model of chronic hepatitis B. Thus, this study paves the way for evaluation of the multi-antigen virus-like vesicles as a tool for immunotherapy of chronic hepatitis B.

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Therapeutic vaccination for chronic hepatitis B

Cited by 65 publications

References 54 publications

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

Therapeutic vaccination for chronic hepatitis B: A systematic review and meta‐analysis

Virus-like vesicles expressing multiple antigens for immunotherapy of chronic hepatitis B

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