Generation and Characterization of a Neutralizing Human Monoclonal  Antibody to Hepatitis B Virus PreS1 from a Phage-Displayed Human Synthetic Fab Library

Jo, Gyunghee; Jeong, Mun Sik; Wi, Jimin; Kim, Doo Hyun; Kim, Sangkyu; Kim, Dain; Yoon, Jun-Yeol; Chae, Heemun; Kim, Kyun-Hwan; Hong, Hyo Jeong

doi:10.4014/jmb.1803.03056

Cited by 12 publications

(19 citation statements)

References 20 publications

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“…Another advantage of this construct over the current vaccines was the coverage of escaped mutants. This feature was derived from the Myrcludex fragment where any mutation in this region reduces the pathogenesis of the virus (64). Also, antibodies produced against this construct can eliminate virus-infected cells using the antibody-dependent cellular cytotoxicity (ADCC) mechanism.…”

Section: Discussionmentioning

confidence: 99%

Computational Design of a Novel VLP-Based Vaccine for Hepatitis B Virus

et al. 2020

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Hepatitis B virus (HBV) is a global virus responsible for a universal disease burden for millions of people. Various vaccination strategies have been developed using viral vector, nucleic acid, protein, peptide, and virus-like particles (VLPs) to stimulate favorable immune responses against HBV. Given the pivotal role of specific immune responses of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in infection control, we designed a VLP-based vaccine by placing the antibody-binding fragments of HBsAg in the major immunodominant region (MIR) epitope of HBcAg to stimulate multilateral immunity. A computational approach was employed to predict and evaluate the conservation, antigenicity, allergenicity, and immunogenicity of the construct. Modeling and molecular dynamics (MD) demonstrated the folding stability of HBcAg as a carrier in inserting Myrcludex and "a" determinant of HBsAg. Regions 1-50 and 118-150 of HBsAg were considered to have the highest stability to be involved in the designed vaccine. Molecular docking revealed appropriate interactions between the B cell epitope of the designed vaccine and the antibodies. Totally, the final construct was promising for inducing humoral and cellular responses against HBV.

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Section: Discussionmentioning

confidence: 99%

Computational Design of a Novel VLP-Based Vaccine for Hepatitis B Virus

et al. 2020

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“…Although site S4 is far from ACE2 binding site, corresponding mAbs P05-5B6 and P05-6H7 can neutralize SARS-CoV and SARS-CoV-2 infection without blocking S protein binding to ACE2, as reported S309 (47). Majority of potently neutralizing antibodies inhibit viral infection by blocking spike proteins attachment with receptors (53)(54)(55), however, we speculate that the site S4 directed mAbs may inhibit SARS-CoV-2 and SARS-CoV infection by intracellular neutralization pathway, a mechanism inhibiting the release of virus within endosome into cytoplasm, as reported in recent studies (40).…”

Section: Similar To Others Virus Infection An Increase In Mabs Binding Activity To Sars-mentioning

confidence: 99%

Quantatitive Analysis of Conserved Sites on the SARS-CoV-2 Receptor-Binding Domain to Promote Development of Universal SARS-Like Coronavirus Vaccines

Wang

Xiong

et al. 2021

Preprint

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Although vaccines have been successfully developed and approved against SARS-CoV-2, it is still valuable to perform studies on conserved antigenic sites for preventing possible pandemic-risk of other SARS-like coronavirus in the future and prevalent SARS-CoV-2 variants. By antibodies obtained from convalescent COVID-19 individuals, receptor binding domain (RBD) were identified as immunodominant neutralizing domain that efficiently elicits neutralizing antibody response with on-going affinity mature. Moreover, we succeeded to define a quantitative antigenic map of neutralizing sites within SARS-CoV-2 RBD, and found that sites S2, S3 and S4 (new-found site) are conserved sites and determined as subimmunodominant sites, putatively due to their less accessibility than SARS-CoV-2 unique sites. P10-6G3, P07-4D10 and P05-6H7, respectively targeting S2, S3 and S4, are relatively rare antibodies that also potently neutralizes SARS-CoV, and the last mAbs performing neutralization without blocking S protein binding to receptor. Further, we have tried to design some RBDs to improve the immunogenicity of conserved sites. Our studies, focusing on conserved antigenic sites of SARS-CoV-2 and SARS-CoV, provide insights for promoting development of universal SARS-like coronavirus vaccines therefore enhancing our pandemic preparedness.

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“…ScFv fragments often have a high tendency to form multimers as well as aggregates and have been found to lose affinity during conversion to Ig (immunoglobulin)G, whereas Fab fragments have been found to possess comparably higher structural stability by the presence of the CH1 and light-chain constant domain (CL), and thus their binding activities were retained after conversion to IgG [32]. We previously generated a human synthetic Fab library based on the VH3-23 and VK1-39 framework pairing and have successfully generated mAbs against recombinant proteins and peptide [33][34][35] In this study, to generate mAbs against the serotype-specific LPS of V. cholerae, we exploited the advantages of phage display technology. We efficiently generated anti-Ogawa mAbs from a human synthetic Fab library and confirmed that they bind to V. cholerae vaccine in a dose-dependent fashion.…”

Section: Vibrio Cholerae Cause Of the Life-threatening Diarrheal Dismentioning

confidence: 99%

Generation and Characterization of Monoclonal Antibodies to the Ogawa Lipopolysaccharide of Vibrio cholerae O1 from Phage-Displayed Human Synthetic Fab Library

Kim

Hong

Choi

et al. 2020

J. Microbiol. Biotechnol.

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Vibrio cholerae , cause of the life-threatening diarrheal disease cholera, can be divided into different serogroups based on the structure of its lipopolysaccharide (LPS), which consists of lipid-A, corepolysaccharide and O-antigen polysaccharide (O-PS). The O1 serogroup, the predominant cause of cholera, includes two major serotypes, Inaba and Ogawa. These serotypes are differentiated by the presence of a single 2- O -methyl group in the upstream terminal perosamine of the Ogawa O-PS, which is absent in the Inaba O-PS. To ensure the consistent quality and efficacy of the current cholera vaccines, accurate measurement and characterization of each of these two serotypes is highly important. In this study, we efficiently screened a phage-displayed human synthetic Fab library by bio-panning against Ogawa LPS and finally selected three unique mAbs (D9, E11, and F7) that specifically react with Ogawa LPS. The mAbs bound to Vibrio cholerae vaccine in a dose-dependent fashion. Sequence and structure analyses of antibody paratopes suggest that IgG D9 might have the same fine specificity as that of the murine mAbs, which were shown to bind to the upstream terminal perosamine of Ogawa O-PS, whereas IgGs F7 and E11 showed some different characteristics in the paratopes. To our knowledge, this study is the first to demonstrate the generation of Ogawa-specific mAbs using phage display technology. The mAbs will be useful for identification and quantification of Ogawa LPS in multivalent V. cholerae vaccines.

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Generation and Characterization of a Neutralizing Human Monoclonal Antibody to Hepatitis B Virus PreS1 from a Phage-Displayed Human Synthetic Fab Library

Cited by 12 publications

References 20 publications

Computational Design of a Novel VLP-Based Vaccine for Hepatitis B Virus

Computational Design of a Novel VLP-Based Vaccine for Hepatitis B Virus

Quantatitive Analysis of Conserved Sites on the SARS-CoV-2 Receptor-Binding Domain to Promote Development of Universal SARS-Like Coronavirus Vaccines

Generation and Characterization of Monoclonal Antibodies to the Ogawa Lipopolysaccharide of Vibrio cholerae O1 from Phage-Displayed Human Synthetic Fab Library

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