Hepatitis B surface antigen on subviral particles reduces the neutralizing effect of anti-HBs antibodies on hepatitis B viral particles in vitro

Rydell, Gustaf E.; Prakash, Kasthuri; Nordér, Helené; Lindh, Magnus

doi:10.1016/j.virol.2017.05.017

Cited by 59 publications

(48 citation statements)

References 12 publications

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“…The full understanding of the contribution of these mechanisms on B cell functionality in CHB infection will be important for selecting the new therapeutic strategies that aim to recover the faulted HBV-specific immunity present in CHB patients and that are now entering clinical trials (23,29,56). Agents designed to reduce secretion or synthesis of HBsAg might indeed restore HBV immune function, since, to our knowledge, our observation that full HBsAg-specific B cell functionality is recovered only at the time of complete negativity of serological HBsAg represents what we believe is the first clear observation that circulating HBsAg acts, in HBV-infected patients, not only as a decoy of anti-HBs Abs (28), but also as a modulator of HBsAgspecific B cell function. On the other hand, the lack of associations between HBsAg quantity and HBsAg-specific B cell defects might indicate that partial suppression of HBsAg quantity cannot be sufficient to recover B cell immunity.…”

Section: Discussionmentioning

confidence: 77%

“…The evolutionary reason that HBV has developed its ability to produce large quantities of subviral, noninfectious particles is still not clear. One attractive hypothesis is that HBsAg functions as a decoy to saturate anti-HBs Abs and so prevents virus neutralization (28). It has also been proposed that HBsAg can suppress innate, humoral, or cellular immunity (29).…”

Section: Introductionmentioning

confidence: 99%

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PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection

Salimzadeh¹,

Bert²,

Dutertre³

et al. 2018

Journal of Clinical Investigation

218

250

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Chronic HBV (CHB) infection suppresses virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a dual-staining method that utilizes hepatitis B virus (HBV) surface antigens (HBsAg) labeled with fluorochromes as "baits" for specific ex vivo detection of HBsAg-specific B cells and analysis of their quantity, function, and phenotype. We studied healthy vaccinated subjects (n = 18) and patients with resolved (n = 21), acute (n = 11), or chronic (n = 96) HBV infection and observed that frequencies of circulating HBsAg-specific B cells were independent of HBV infection status. In contrast, the presence of serum HBsAg affected function and phenotype of HBsAg-specific B cells that were unable to mature in vitro into Ab-secreting cells and displayed an increased expression of markers linked to hyperactivation (CD21lo) and exhaustion (PD-1). Importantly, B cell alterations were not limited to HBsAg-specific B cells, but affected the global B cell population. HBsAg-specific B cell maturation could be partially restored by a method involving the combination of the cytokines IL-2 and IL-21 and CD40L-expressing feeder cells and was further boosted by the addition of anti-PD-1 Abs. In conclusion, HBV infection has a marked impact on global and HBV-specific humoral immunity, yet HBsAg-specific B cells are amenable to a partial rescue by B cell-maturing cytokines and PD-1 blockade.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection

Salimzadeh¹,

Bert²,

Dutertre³

et al. 2018

Journal of Clinical Investigation

218

250

View full text Add to dashboard Cite

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“…SVPs exceed the presence of infectious virions in host sera by a factor between 10 2 and 10 5 [17,[21][22][23][24]. SVPs are predominately composed of HBsAgS, and their presence in the sera does not seem to interfere with HBV particle entry into hepatocytes, suggesting that SVPs represent decoys by binding to virus-neutralizing antibodies [25]. HBsAgS SVPs share important immunological determinants with the mature virus, and therefore, SVPs derived from patient serum or recombinant SVPs represent effective immunogens for the induction of a protective immune response [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Jeevan-Raj

Netter

2020

Viruses

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Hepatitis B remains one of the major global health problems more than 40 years after the identification of human hepatitis B virus (HBV) as the causative agent. A critical turning point in combating this virus was the development of a preventative vaccine composed of the HBV surface (envelope) protein (HBsAg) to reduce the risk of new infections. The isolation of HBsAg sub-viral particles (SVPs) from the blood of asymptomatic HBV carriers as antigens for the first-generation vaccines, followed by the development of recombinant HBsAg SVPs produced in yeast as the antigenic components of the second-generation vaccines, represent landmark advancements in biotechnology and medicine. The ability of the HBsAg SVPs to accept and present foreign antigenic sequences provides the basis of a chimeric particulate delivery platform, and resulted in the development of a vaccine against malaria (RTS,S/AS01, MosquirixTM), and various preclinical vaccine candidates to overcome infectious diseases for which there are no effective vaccines. Biomedical modifications of the HBsAg subunits allowed the identification of strategies to enhance the HBsAg SVP immunogenicity to build potent vaccines for preventative and possibly therapeutic applications. The review provides an overview of the formation and assembly of the HBsAg SVPs and highlights the utilization of the particles in key effective vaccines.

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“…Moreover, chronic infection with the HBV is typically established neonatally and progresses during the phase of immune tolerance. The non-infectious subviral particles, which are produced in several fold excess to the infectious Dane particle, soak up the antibodies produced during natural humoral response and protects the virus from being neutralized (Rydell et al, 2017). These decoys are typically composed of small HBs that lacks the neutralizing epitope preS1 and therefore trigger the production of excess amounts non-PreS1 targeting antibodies.…”

Section: Discussionmentioning

confidence: 99%

Engineering Cellular Biosensors with Customizable Antiviral Responses Targeting Hepatitis B Virus

et al. 2020

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SynNotch receptor technology is a versatile tool that uses the regulatory notch core portion with an extracellular scFv and an intracellular transcription factor that enables to program customized input and output functions in mammalian cells. In this study, we designed a novel synNotch receptor comprising scFv against HBs antigen linked with an intracellular artificial transcription factor and exploited it for viral sensing and cellular immunotherapy. The synNotch receptor expressing cells sensed HBV particles and membrane-bound HBs antigens and responded by expressing reporter molecules, secNL or GFP. We also programmed these cells to dispense antiviral responses such as type I interferon and anti-HBV neutralizing mouse-human chimeric antibodies. Our data reveal that synNotch receptor signaling works for membrane-bound ligands such as enveloped viral particles and proteins borne on liposomal vesicles. This study establishes the concepts of ''engineered immunity'' where the synNotch platform is utilized for cellular immunotherapy against viral infections.

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Hepatitis B surface antigen on subviral particles reduces the neutralizing effect of anti-HBs antibodies on hepatitis B viral particles in vitro

Cited by 59 publications

References 12 publications

PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection

PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Engineering Cellular Biosensors with Customizable Antiviral Responses Targeting Hepatitis B Virus

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