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. 2015 Apr 29;10(4):e0125704.
doi: 10.1371/journal.pone.0125704. eCollection 2015.

A Human Monoclonal Antibody against Hepatitis B Surface Antigen with Potent Neutralizing Activity

Antonella Cerino  1 , Corinna M Bremer  2 , Dieter Glebe  2 , Mario U Mondelli  3
Affiliations

A Human Monoclonal Antibody against Hepatitis B Surface Antigen with Potent Neutralizing Activity

Antonella Cerino et al. PLoS One. .

Abstract

We describe the production and characterization of human monoclonal antibodies (mAb) specific for the major hepatitis B virus (HBV) S protein. The mAbs, two IgG1κ and one IgG1λ, were secreted by B-cell clones obtained from peripheral blood mononuclear cells (PBMC) of one person convalescent from acute hepatitis B and one vaccinated individual. The former recognized a denaturation-insensitive epitope within the p24 protein whereas the latter recognized a denaturation-sensitive, conformational epitope located within the HBsAg common "a" determinant. This mAb, denominated ADRI-2F3, displayed a very high protective titer of over 43,000 IU/mg mAb and showed an extremely potent neutralizing activity in the in vitro model of HBV infection using primary hepatocytes from Tupaia belangeri as target. Recombinant variable heavy and light domain sequences derived from mAb ADRI-2F3 were cloned into eukaryotic expression vectors and showed identical fine specificity and 1 log10 higher titer than the original IgG1λ. It is envisaged that such mAb will be able to efficiently prevent HBV reinfection after liver transplantation for end-stage chronic HBV infection or infection after needle-stick exposure, providing an unlimited source of valuable protective anti-HBs antibody.

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Conflict of interest statement

Competing Interests: Co-author Mario U. Mondelli is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria.

Figures

Fig 1
Fig 1. A) Titration curve of humAb binding to HBsAg in an ELISA.
Diamonds: ADRI-2F3, Squares: PK-3D1, Triangles PK-10C7. B) Western blot showing reactivity of humAb ADRI-2F3 (lanes 1 and 2), PK-10C7 (lane 3) and PK-3D1 (lane 4). Lane 5; positive control serum, lane 6; negative control. MW indicates a molecular weight marker. Note that in lanes 3, 4 and 5 a 24 kDa band is recognized, indicating binding to the HBsAg polypeptide. C) Competitive inhibition of serial dilutions (0 ng/ml—400 ng/ml) of humAb ADRI-2F3, and its corresponding recombinant recADR12F3, binding to HBsAg by 200 ng of murine mAb Hyb-824 specific for the HBsAg common “a” determinant. D) Competitive inhibition of humAb ADRI-2F3, recADRI2F3, PK-10C7, PK-3D1 by murine mAb Hyb-824. CM3B6, a HCV-NS3 specific humAb, served as negative control. Co20-F10 is an isotype control.
Fig 2
Fig 2. Neutralizing activity of three human monoclonal antibodies PK-3D1, PK-10C7 and ADRI-2F3 in comparison with mouse monoclonal antibody MA18/7.
It is shown herein that a dilution of 1:10,000 of monoclonal antibody supernatant ADRI-2F3 completely neutralizes the activity of HBV, whereas EC50 is reached at a dilution of 1: 100,000.
Fig 3
Fig 3. Reactivity of recombinant antibody ADRI-2F3 versus human monoclonal ADRI-2F3.
The titration curve shows that the recombinant antibody is about 10 times more reactive than the original human monoclonal antibody.
See this image and copyright information in PMC

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