Monoclonal antibodies to various epitopes of hepatitis <scp>B</scp> surface antigen inhibit hepatitis <scp>B</scp> virus infection

Shirazi, Forough Golsaz; Mohammadi, Hamed; Amiri, Mohammad Mehdi; Singethan, Katrin; Xia, Yuchen; Bayat, Ali Ahmad; Bahadori, Motahareh; Rabbani, Hodjatallah; Jeddi-Tehrani, Mahmood; Protzer, Ulrike; Shokri, Fazel

doi:10.1111/jgh.12483

Cited by 18 publications

(5 citation statements)

References 34 publications

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“…This convinced us to use our flow cytometry staining protocol for the isolation of single HBsAg-specific memory B cells for antibody generation, yielding a total of 20 novel human mAbs, with 4D06 and 4D08 showing the highest affinity for HBsAg. EC 50 values were in a nanomolar range comparable to other previously published anti-HBs-reactive mAbs ( 29 , 34 , 47 ).…”

Section: Discussionsupporting

confidence: 84%

“…In this study, we describe a fast and efficient method to identify fully human HBV-specific monoclonal antibodies from donors with resolved infection using single B-cell sorting technology, which is subsequently used to generate chimeric antigen receptors for the use in adoptive T-cell therapy of hepatitis B virus infection or HBV-induced hepatocellular carcinoma. To date, different approaches have been used for the generation of HBV-specific mAbs, mostly using classical hybridoma technology ( 29 , 34 – 36 ), phage display technologies ( 37 , 38 ) or immortalization of human peripheral blood B cells with Epstein-Barr virus ( 39 , 40 ). However, these methods have drawbacks, such as the high probability of inducing harmful immune responses in humans against murine protein sequences or the rather inefficient process of B-cell immortalization ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

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CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells

Schreiber,

Dressler,

Loffredo-Verde

et al. 2024

Front. Immunol.

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To design new CARs targeting hepatitis B virus (HBV), we isolated human monoclonal antibodies recognizing the HBV envelope proteins from single B cells of a patient with a resolved infection. HBV-specific memory B cells were isolated by incubating peripheral blood mononuclear cells with biotinylated hepatitis B surface antigen (HBsAg), followed by single-cell flow cytometry-based sorting of live, CD19+ IgG+ HBsAg+ cells. Amplification and sequencing of immunoglobulin genes from single memory B cells identified variable heavy and light chain sequences. Corresponding immunoglobulin chains were cloned into IgG1 expression vectors and expressed in mammalian cells. Two antibodies named 4D06 and 4D08 were found to be highly specific for HBsAg, recognized a conformational and a linear epitope, respectively, and showed broad reactivity and neutralization capacity against all major HBV genotypes. 4D06 and 4D08 variable chain fragments were cloned into a 2nd generation CAR format with CD28 and CD3zeta intracellular signaling domains. The new CAR constructs displayed a high functional avidity when expressed on primary human T cells. CAR-grafted T cells proved to be polyfunctional regarding cytokine secretion and killed HBV-positive target cells. Interestingly, background activation of the 4D08-CAR recognizing a linear instead of a conformational epitope was consistently low. In a preclinical model of chronic HBV infection, murine T cells grafted with the 4D06 and the 4D08 CAR showed on target activity indicated by a transient increase in serum transaminases, and a lower number of HBV-positive hepatocytes in the mice treated. This study demonstrates an efficient and fast approach to identifying pathogen-specific monoclonal human antibodies from small donor cell numbers for the subsequent generation of new CARs.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells

Schreiber,

Dressler,

Loffredo-Verde

et al. 2024

Front. Immunol.

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“…HBV is one of the main causes of hepatic decompensation, cirrhosis, and hepatocellular carcinoma (HCC) (1, 2). Worldwide, more than two billion people are infected with HBV and approximately 400 million people are HBV carriers; of these, 75% are Asian (3, 4).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Knowledge, Attitudes, and Prevalence of Hepatitis B and C Seromarkers Among Barbers in Tehran

et al. 2016

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BackgroundHepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health problem in the world. Hairdressers (barbers) are in continuous contact with scissors and blades, and are considered a high-risk group for these infections.ObjectivesThe aim of this study was to analyze the prevalence of hepatitis B and C infections in barbers in Tehran and to evaluate their attitudes and knowledge about the occupational risk of these infections.MethodsSix hundred eleven barbers were included in this study. A group of 556 bakers were also selected from the same regions, as a low-risk control group. Serum levels of hepatitis B surface antigen (HBsAg), HBsAg-specific antibody (HBsAb), hepatitis B core antigen-specific antibody (HBcAb), and hepatitis C virus-specific (anti-HCV) antibody markers were measured with the enzyme-linked immunosorbent assay (ELISA). Participants were interviewed using a questionnaire consisting of four sections: demographic information, awareness, behavior, and personal attitudes.ResultsThere were no significant differences in the frequency of HBsAg between the two groups. However, the frequency of HCV Ab in barbers was significantly higher than that in bakers (P < 0.005). In addition, the frequency of HBsAb marker in barbers was significantly correlated with increased awareness (P < 0.05) and number of tattoos (P < 0.001). HBcAb marker was significantly correlated with age (P < 0.001) and duration of professional career (P < 0.005). With age, barbers’ attitudes improved significantly (P < 0.05).ConclusionsBeing a barber alone is not a potential risk factor for HBV infection, while HCV infection is still an occupational health hazards for barbers. We suggest more extensive case-control studies with regard to rates of hepatitis B and C markers among barbers in other Iranian cities to assess the incidence of hepatitis B and C infections among this population.

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“…Thus, mABs can help prevent it from infecting new cells and spreading throughout the body. This is in contrast to existing HBV therapies, which primarily focus on suppressing viral replication via genetic alteration rather than preventing spread via a physiologic response [27]. Monoclonal antibodies may also induce other immune responses against HBV.…”

Section: Examples Of Antibody Treatment Mechanisms Applied In Current...mentioning

confidence: 97%

“…It takes a significant amount of time to create hybridoma cells, harvest their antibodies, and identify the rare antibody binders used in this technique [37]. Some methods are limited by functional barriers, such as the high cost of screening for antibodies with high throughput [27,38]. Other methods are prone to technical shortcomings.…”

Section: Obstacles In Developmentmentioning

confidence: 99%

Monoclonal War: The Antibody Arsenal and Targets for Expanded Application

Rosenn,

Benhaim,

Siegel

et al. 2023

Immuno

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Advancements in sequencing and screening technology have made monoclonal antibodies more accessible, cost-effective, and precise. These drugs effectively target pathogens and cancer cells and even regulate metabolic pathways by focusing on specific intermediates. Monoclonal antibodies play a key role in mitigating a rise in occupation-related cancers, neurodegenerative disorders, and multidrug-resistant organisms. Here, we review the origins, mechanisms, and applications of this important drug class and explore future avenues for research.

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Monoclonal antibodies to various epitopes of hepatitis B surface antigen inhibit hepatitis B virus infection

Cited by 18 publications

References 34 publications

CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells

CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells

Analysis of Knowledge, Attitudes, and Prevalence of Hepatitis B and C Seromarkers Among Barbers in Tehran

Monoclonal War: The Antibody Arsenal and Targets for Expanded Application

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