A bispecific antibody against two different epitopes on hepatitis B surface antigen has potent hepatitis B virus neutralizing activity

Tan, Wenlong; Meng, Yanchun; Li, Hui; Yang, Chunxu; Han, Siqi; Zeng, Jing; Huang, Ang; Li, Bohua; Zhang, Yanyun; Guo, Yajun

doi:10.4161/mabs.26390

Cited by 22 publications

(17 citation statements)

References 35 publications

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“…Recently, we engineered a bispecific antibody using 2 different mAbs against hepatitis B surface antigen. 18 This bispecific antibody showed significantly more potent HBV-neutralizing activity compared with the combination of both parental monoclonal antibodies. 18 We also developed a bispecific anti-ErbB2 antibody using trastuzumab and pertuzumab, 2 ErbB2-specific humanized antibodies that bind to different epitopes on ErbB2.…”

Section: Discussionmentioning

confidence: 90%

“…18 This bispecific antibody showed significantly more potent HBV-neutralizing activity compared with the combination of both parental monoclonal antibodies. 18 We also developed a bispecific anti-ErbB2 antibody using trastuzumab and pertuzumab, 2 ErbB2-specific humanized antibodies that bind to different epitopes on ErbB2. 30 TP L showed superior ErbB2 heterodimerization-blocking activity over the combination of both parental monoclonal antibodies.…”

Section: Discussionmentioning

confidence: 90%

“…17 Our previous studies have shown that a bispecific antibody engineered from 2 distinct monoclonal antibodies against hepatitis B surface antigen (HBsAg) had superior HBV-neutralizing activity compared with the combination of both parental monoclonal antibodies, possibly through steric hindrance or induction of HBsAg conformational changes. 18 In this study, we constructed a bispecific antibody using the anti-DENV mAbs 1A1D and 2A10. This bispecific antibody, denoted as DVD-1A1D-2A10, was confirmed to be more effective at neutralizing DENV than its parental mAbs, and even better than the combination of them.…”

Section: Introductionmentioning

confidence: 99%

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A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion

Shi

Deng

Wang

et al. 2016

mAbs

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(2016) A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion, mAbs, 8:3, 574-584, DOI: 10.1080/19420862.2016 To link to this article: https://doi.org/10. 1080/19420862.2016 ABSTRACTAlthough dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E-DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane.Our data showed that DVD-1A1D-2A10 retained the antigen-binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-g-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion

Shi

Deng

Wang

et al. 2016

mAbs

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“…Guo and colleagues engineered a dual variable domain (DVD) bispecific antibody from 2 distinct monoclonal antibodies against hepatitis B surface antigen (HBsAg) that synergistically neutralized hepatitis B virus (HBV) infection. 21 In DVDs the v H and v L of one antibody are genetically fused to the N-terminus of the heavy and light chain of a second antibody via a short peptide linker, respectively, thereby retaining the Y-shape of an IgG molecule (Fig. 1B).…”

Section: Bispecific Antibodies Targeting 2 Distinct Viral Epitopesmentioning

confidence: 99%

Bispecific antibodies for viral immunotherapy

Nyakatura

Soare

Lai

2017

Human Vaccines & Immunotherapeutics

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Bispecific antibody engineering, in which binding specificities toward 2 distinct epitopes are combined into a single molecule, can greatly enhance immunotherapeutic properties of monoclonal antibodies. While the bispecific antibody approach has been applied widely to targets for indications such as cancer and inflammation, the development of such agents for viral immunotherapy is only now emerging. Here, we review recent advances in the development of bispecific antibodies for viral immunotherapy, highlighting promising in vitro and in vivo results.

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“…The binding was measured as response units; and the results were analyzed with the Langmuir binding model using BIAevaluation software 4.1 (Figure 6 affinity of Lig7 to HBsAg is much higher than the affinity of the anti-HBsAg scFv (23 mM) developed by Xiong [37]. When compared to monoclonal antibodies developed against HBsAg, Lig7 scFv is within the range of high HBsAg affinity [38,39]. Therefore, as a single-chain variable fragment, the Lig7 clone has the potential to be used for diagnostic applications.…”

Section: Soluble Expression and Characterization Of Antihbsag Scfvmentioning

confidence: 99%

Cloning of anti-HBsAg single-chain variable fragments from hybridoma cells for one-step ELISA

Erdağ

Balcıoğlu

Bahadır

et al. 2017

Biotechnology & Biotechnological Equipment

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Hepatitis B virus (HBV) infection is a worldwide health problem. More than 400 million people are chronic HBV carriers in the world. Infected individuals are at a high risk of developing liver cirrhosis and hepatocellular carcinoma as the main consequences of HBV. The discoveries of fast diagnostic systems and new therapeutic applications are crucial in the fight against viral hepatitis. In this paper we present the generation of a single-chain variable fragment (scFv) from a mouse monoclonal antibody specific to the HBV surface antigen (HBsAg) and demonstrate its expression as a bacterial alkaline phosphatase (AP) fusion protein. In this study, we constructed scFvs from hybridoma cells expressing HBsAg-specific antibody using phage display technology and expressed them in Escherichia coli. The anti-HBsAg scFvs were inserted into pQE-2 vector to produce scFv antibody genetically fused to bacterial AP. Reproducibility of the recombinant HBsAg-scFv fusion protein was tested using Enzyme-linked Immunosorbent Assay (ELISA). Present preliminary findings indicate that the anti-HBsAg-scFv AP conjugate could be further used for the development of one-step ELISA for the detection of HBV.

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A bispecific antibody against two different epitopes on hepatitis B surface antigen has potent hepatitis B virus neutralizing activity

Abstract: (2013) A bispecific antibody against two different epitopes on hepatitis B surface antigen has potent hepatitis B virus neutralizing activity, mAbs, 5:6, 946-955,

Cited by 22 publications

References 35 publications

A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion

A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion

Bispecific antibodies for viral immunotherapy

Cloning of anti-HBsAg single-chain variable fragments from hybridoma cells for one-step ELISA

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