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  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Clinical Research Nurse
  • Clinician Researcher
  • Department Manager
  • Dual-education Student
  • Full Professor
  • Honorary Professor
  • Lab assistant
  • Master Student
  • Non-permanent Researcher
  • Nursing Staff
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Prize
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
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← Go to Research

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Scientific Fields
Diseases
Organisms
Applications
Technique
Starting Date
18
Apr 2021
Status
Ongoing
Members
2
Structures
4
Publications
1

About

HBV infection can be successfully controlled by natural immune responses in more than 90% of the patients infected as adults, and in the ~1% of chronically infected patients who spontaneously clear the infection (also called HBV seroconverters), as defined by HBs antigen loss and anti-HBs antibody seroconversion.

To better understand the memory B-cell immunity to HBV and identify cross-neutralizing epitopes on the HBS surface antigen (HBsAg), we single-cell FACS captured HBsAg-specific memory B cells from HBV vaccinees and seroconverters, cloned and characterized 73 anti-HBV mAbs. We found that most HBV-specific memory B cells: (i) displayed a biased immunoglobulin repertoire; (ii) expressed surface IgG recognizing conformational epitopes; (iii) cross-reacted against various HBV genotypes and naturally-occurring escape mutants. Importantly, 61% of the HBV mAbs neutralized HBV infection in vitro and among those, half were extremely potent (IC50s ~ pg/ml). Finally, we identified at least six non-overlapping neutralizing epitopes on HBsAg. Using two different mouse models of HBV infection, we demonstrated that immunotherapy with a potent HBV bNAb, Bc1.187, can suppress viraemia in vivo. Altogether, our data indicate that the memory B-cell response to HBsAg in HBV vaccinees and seroconverters is diverse in terms of gene repertoire, targeted epitopes and neutralizing activity. Thus, human neutralizing HBsAg antibodies appear to play a key role in the spontaneous control of HBV and represent promising immunotherapeutic tools for achieving a functional cure in chronic HBV carriers. | Hehle*, Beretta* et al, J Exp Med 2020 |.

Figure. Therapeutic activity of HBV bNAb Bc1.187 in HBV-carrier (A) and HBV-infected humanized liver (B) mouse models.  n: number of mice. The red line indicates the average.

Fundings