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Antibodies
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Unravelling Effector Functions of B cells in Infectious Diseases and...
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Unravelling Effector Functions of B cells in Infectious Diseases and Cancer

A special issue of Antibodies (ISSN 2073-4468). This special issue belongs to the section "Humoral Immunity".

Deadline for manuscript submissions: closed (30 June 2025) | Viewed by 4968

Special Issue Editor

Dr. Farhat Afrin

E-Mail Website
Guest Editor
JIS Institute of Advanced Studies and Research, JIS University, Arch Waterfront, Salt Lake, Sector V, GP Block, Kolkata 700091, India
Interests: immunotherapy; antigenic modulation; vaccine; biotherapeutic drugs

Special Issue Information

Dear Colleagues,

Infectious diseases cause significant morbidity and mortality worldwide, particularly in low- and middle-income countries. Antibodies are the cardinal effector molecules of the adaptive immune system and are being leveraged as biotherapeutic drugs against bacterial, parasitic and viral diseases and cancer. Besides direct neutralization, antibodies induce innate and adaptive immune responses (through their Fc domain) that are critical to a successful host immune response against infections as in AIDS, Ebola, malaria, influenza, tuberculosis and a host of other diseases. Diverse effector functions are deployed by antibodies such as immune complex formation that drive sequestration and uptake of pathogens, elimination of infected cells, enhancement of antigen presentation and regulation of inflammation. The antibody responses are stimulated by infected cells or parasites in the mammalian hosts and may be disease-promoting or protective depending upon the invading parasite species and the antibody isotype stimulated. The protective antibodies may inhibit parasite invasion and hence its growth via antibody-dependent cellular cytotoxicity and complement-fixing antibodies as in the case of Plasmodium species that cause malaria. Antibodies have been reported to block the entry of cestodes like Taenia and Echinococcus into the mammalian host. While intracellular parasites such as Toxoplasma, Entamoeba and Leishmania species persist in the hostile milieu of the host by mitigating the antibody effector functions. Tailored monoclonal antibody-based therapeutics may help in designing effective vaccines against these infections and cancer. The affinity and avidity of engineered antibody formats may also be tuned to enable a new wave of differentiated antibody drugs with tailored properties and novel functions, as promising treatment options for a wide variety of diseases.

This book will focus on antibodies leveraging a remarkable diversity of anti-microbial processes locked within our immune system, and the specific antibody effector functions that can be harnessed to facilitate the diagnosis, treatment and prevention of infections. The amelioration of antibody effector functions will also be discussed that may guide a rational vaccine design and antibody-based therapeutics to target gaps in our infectious disease armamentarium.

Dr. Farhat Afrin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antibody-based therapeutics
  • effector functions
  • infectious diseases
  • antibody isotypes
  • antibody-dependent cellular cytotoxicity
  • complement fixation
  • inflammation
  • vaccines
  • engineered antibodies
  • antigen presentation
  • cancer

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Published Papers (4 papers)

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Research

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18 pages, 5023 KB  
Article
Developing a 3D Model Culture of an EBV+/CD30+ B-Anaplastic Large Cell Lymphoma Cell Line to Assay Brentuximab Vedotin Treatment
by Paolo Giannoni, Gabriella Pietra, Orlando Izzo, Giuseppina Fugazza, Roberto Benelli, Alessandro Poggi, Mauro Krampera, Chiara Utzeri, Monica Marchese, Marco Musso, Paola Visconti and Daniela de Totero
Antibodies 2025, 14(4), 98; https://doi.org/10.3390/antib14040098 - 10 Nov 2025
Viewed by 198
Abstract
Background/Objectives: Three-dimensional (3D) in vitro cell culture models have recently stimulated great interest since they may have more pre-clinical value than conventional in vitro 2D models. In fact, 3D culture models may mimic the in vivo biophysical 3D structure of tumors and cell-to-cell [...] Read more.
Background/Objectives: Three-dimensional (3D) in vitro cell culture models have recently stimulated great interest since they may have more pre-clinical value than conventional in vitro 2D models. In fact, 3D culture models may mimic the in vivo biophysical 3D structure of tumors and cell-to-cell interaction, thereby representing a more useful approach to testing drug responses. In this study we have developed a 3D culture model of an EBV+/CD30+cell line, D430B, previously characterized as an Anaplastic Large Cell Lymphoma of B phenotype (B-ALCL), to determine the cytotoxic activity of the antibody–drug conjugate Brentuximab Vedotin. Methods: By using of ultra-low attachment plates, we developed D430B spheroids that appeared particularly homogenous in terms of growth and size. Results: Brentuximab Vedotin treatment (1 to 20 μg/mL) turned out to be significantly cytotoxic to these cells, while the addition of the anti-CD20 chimeric antibody Rituximab (10 μg/mL) appeared almost ineffective, even though these cells express CD20. Moreover, when we co-cultured D430B cells with stromal cells (HS5), to re-create a microenvironment representative of neoplastic cell/mesenchymal cell interactions within the lymph node, we observed a significant, although faint, protective effect. Conclusions: This simple and reproducible method of generating D430B-ALCL spheroids to evaluate their response to Brentuximab Vedotin treatment, as here described, may provide a valuable preliminary tool for the future pre-clinical screening of patients’ primary lymphoma cells or the development of novel therapies for this type of pathology and related diseases. Full article
(This article belongs to the Special Issue Unravelling Effector Functions of B cells in Infectious Diseases and Cancer)
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22 pages, 5945 KB  
Article
Immunogenicity Risk Assessment of Biotherapeutics Using an Ex Vivo B Cell Assay
by Kevin M. Budge, Ross Blankenship, Patricia Brown-Augsburger and Lukasz K. Chlewicki
Antibodies 2025, 14(3), 62; https://doi.org/10.3390/antib14030062 - 22 Jul 2025
Cited by 1 | Viewed by 1771
Abstract
Background/Objectives: Anti-drug antibody (ADA) formation can impact the safety, pharmacokinetics, and/or efficacy of biotherapeutics, including monoclonal antibodies (mAbs). Current strategies for ADA/immunogenicity risk prediction of mAbs include in silico algorithms, T cell proliferation assays, MHC-associated peptide proteomics assays (MAPPs), and dendritic cell internalization [...] Read more.
Background/Objectives: Anti-drug antibody (ADA) formation can impact the safety, pharmacokinetics, and/or efficacy of biotherapeutics, including monoclonal antibodies (mAbs). Current strategies for ADA/immunogenicity risk prediction of mAbs include in silico algorithms, T cell proliferation assays, MHC-associated peptide proteomics assays (MAPPs), and dendritic cell internalization assays. However, B cell-mediated responses are not assessed in these assays. B cells are professional antigen-presenting cells (APCs) and secrete antibodies toward immunogenic mAbs. Therefore, methods to determine B cell responses would be beneficial for immunogenicity risk prediction and may provide a more comprehensive assessment of risk. Methods: We used a PBMC culture method with the addition of IL-4, IL-21, B cell activating factor (BAFF), and an anti-CD40 agonist mAb to support B cell survival and activation. Results: B cells in this assay format become activated, proliferate, and secrete IgG. A panel of 51 antibodies with varying clinical immunogenicity rates were screened in this assay with IgG secretion used as a readout for immunogenicity risk. IgG secretion differed among test articles but did not correlate with the clinical immunogenicity rating. Conclusions: This dataset highlights the challenges of developing a B cell assay for immunogenicity risk prediction and provides a framework for further refinement of a B cell-based assay for immunogenicity risk prediction of mAbs. Full article
(This article belongs to the Special Issue Unravelling Effector Functions of B cells in Infectious Diseases and Cancer)
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21 pages, 4090 KB  
Article
Influence of High Eimeria tenella Immunization Dosages on Total Oocyst Output and Specific Antibodies Recognition Response in Hybrid Pullets (Gallus gallus)—A Pilot Study
by Marco A. Juarez-Estrada, Guillermo Tellez-Isaias, Víctor M. Petrone-Garcia, Amanda Gayosso-Vazquez, Xochitl Hernandez-Velasco and Rogelio A. Alonso-Morales
Antibodies 2025, 14(1), 9; https://doi.org/10.3390/antib14010009 - 26 Jan 2025
Viewed by 1311
Abstract
Background: Two high primary-immunization doses of a wild-type E. tenella strain were assessed in healthy pullets (5K versus 10K sporulated oocysts/bird) to understand the effects of coccidia infection. Methods: Acquired immunity was evaluated following primary immunization and two booster doses with the homologous [...] Read more.
Background: Two high primary-immunization doses of a wild-type E. tenella strain were assessed in healthy pullets (5K versus 10K sporulated oocysts/bird) to understand the effects of coccidia infection. Methods: Acquired immunity was evaluated following primary immunization and two booster doses with the homologous strain. Total oocyst shedding, clinical signs, and viability of every bird/group after each immunization/booster were recorded. Indirect ELISA measured the time course of humoral responses from each immunization group against sporozoite and second-generation merozoite of E. tenella. Antigen pattern recognition on these two asexual zoite stages of E. tenella was analyzed using Western blotting with antibodies from each immunization program. Afterwards, antigen recognition of specific life-cycle stages was performed using individual pullet serums from the best immunization program. Results: A primary-immunization dose of 1 × 104 oocysts/bird reduced the oocyst output; however, all pullets exhibited severe clinical signs and low specific antibodies titers, with decreased polypeptide recognition on both E. tenella asexual zoite stages. In contrast, immunization with 5 × 103 oocysts/bird yielded the best outcomes regarding increased oocyst collection and early development of sterilizing immunity. After the first booster dosage, this group’s antisera revealed a strong pattern of specific antigen recognition on the two assayed E. tenella life-cycle stages. Conclusions: The E. tenella-specific antibodies from the 5 × 103 oocysts/bird immunization program can aid in passive immunization trials and further research to identify B-cell immunoprotective antigens, which could help in the development of a genetically modified anticoccidial vaccine. Full article
(This article belongs to the Special Issue Unravelling Effector Functions of B cells in Infectious Diseases and Cancer)
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Review

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16 pages, 998 KB  
Review
Influence and Role of Regulatory B Cells in Organ Transplantation: The State of the Art, Prospects, and Emerging Insights
by Marina Fernández-González, Santiago Llorente, José Antonio Galián, Carmen Botella, Rosana González-López, María José Alegría, Alicia Hita, María Rosa Moya-Quiles, Helios Martinez-Banaclocha, Manuel Muro-Pérez, Javier Muro, Alfredo Minguela, Isabel Legaz and Manuel Muro
Antibodies 2025, 14(4), 95; https://doi.org/10.3390/antib14040095 - 7 Nov 2025
Viewed by 223
Abstract
B cells have attracted increasing interest in the field of organ transplantation due to their newly discovered immunoregulatory properties in alloimmune responses. Traditionally, B cells have been primarily associated with adaptive immunity to foreign substances and alloreactive immune response to allografts, differentiating into [...] Read more.
B cells have attracted increasing interest in the field of organ transplantation due to their newly discovered immunoregulatory properties in alloimmune responses. Traditionally, B cells have been primarily associated with adaptive immunity to foreign substances and alloreactive immune response to allografts, differentiating into antibody-producing plasma cells or memory cells upon antigen recognition and T cell collaboration. However, the existence of B cells with regulatory functions (Bregs) in humans has been widely confirmed, highlighting the presence of this subset, which has immunosuppressive properties and which might contribute to allograft tolerance, within the B cell compartment in humans and mice. In this mini review, we summarize all the information available in the published reports about the role of regulatory B cells in solid organ transplantation. Full article
(This article belongs to the Special Issue Unravelling Effector Functions of B cells in Infectious Diseases and Cancer)
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