Development of Therapeutic Antibodies against Toxins and Pathogens

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 27323

Special Issue Editors

Antibody Engineering Group, The Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 74100, Israel
Interests: antibody engineering; therapeutic antibodies; phage display; affinity maturation; fc functions; neutralizing antibodies; vaccines; epitope mapping; fc-chimeric proteins; biosensors; immunoassays; immunoglobulin gene repertoire
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA
Interests: plant and bacterial toxins; antibodies; vaccines; pathophysiology; biodefense
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, monoclonal antibodies have been among one of the largest groups of biotherapeutic proteins approved for the treatment of a wide variety of clinical conditions. In particular, numerous antibodies have been shown to be effective against toxins and infectious diseases (bacteria and viruses). Many of these antibodies are undergoing clinical trials and several have already been approved. The design and clinical application of monoclonal antibody therapeutics for the treatment of toxins and pathogens requires the identification of relevel targets on the surface of the pathogen, gaining in-depth understanding of the pathogen’s mode-of-action, in addition to extensive antibody engineering and modification.

This Special Issue on "Development of Therapeutic Antibodies against Toxins and Pathogens” will bring state-of-the-art original manuscripts and reviews covering all applications of antibody-based therapeutics of toxins and pathogens. The topics included in this issue are novel target antigens, pharmacokinetic/pharmacodynamics studies, in vitro and in vivo applications, biochemical characterization of antibodies, the use of antibodies for the detection of toxins and pathogens, antibody design and parameters affecting antibody activity, clinical studies and many more.

Dr. Ohad Mazor
Dr. Nicholas J. Mantis
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

  • Antibodies
  • Toxins
  • Infectious diseases
  • Pathogens
  • Immunotherapy
  • Antibody engineering
  • pharmacokinetics/pharmacodynamics

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

9 pages, 2170 KiB  
Article
Mapping Immunodominant Antibody Epitopes of Abrin
Antibodies 2020, 9(2), 11; https://doi.org/10.3390/antib9020011 - 27 Apr 2020
Cited by 3 | Viewed by 3838
Abstract
Abrin, a toxin isolated from the seeds of Abrus precatorius (jequirity pea) is considered a biological threat agent by the Center for Disease Control and Prevention. To date, there is no effective postexposure treatment for abrin poisoning, and efforts are being made to [...] Read more.
Abrin, a toxin isolated from the seeds of Abrus precatorius (jequirity pea) is considered a biological threat agent by the Center for Disease Control and Prevention. To date, there is no effective postexposure treatment for abrin poisoning, and efforts are being made to develop an efficient vaccine and measures for postexposure therapy. Epitope mapping is widely applied as an efficient tool for discovering the antigenic moieties of toxins, thus providing invaluable information needed for the development of vaccines and therapies. Aiming to identify the immunodominant epitopes of abrin, several neutralizing antiabrin polyclonal antibodies were screened using a set of 15-mer peptides spanning the amino acid sequence of either the A or B subunits of abrin. Analysis of the antibody-binding pattern revealed 11 linear epitopes for the A subunit and 14 epitopes for the B subunit that are located on the surface of the toxin and thus accessible for antibody interactions. Moreover, the spatial location of several of these epitopes suggests they may block the galactose-binding pockets or the catalytic domain, thus neutralizing the toxin. These findings provide useful information and suggest a possible strategy for the development and design of an improved abrin-based vaccine and therapeutic antibodies. Full article
(This article belongs to the Special Issue Development of Therapeutic Antibodies against Toxins and Pathogens)
Show Figures

Figure 1

17 pages, 3303 KiB  
Article
Human IgA Monoclonal Antibodies That Neutralize Poliovirus, Produced by Hybridomas and Recombinant Expression
Antibodies 2020, 9(1), 5; https://doi.org/10.3390/antib9010005 - 28 Feb 2020
Cited by 7 | Viewed by 6671
Abstract
Poliovirus (PV)-specific intestinal IgAs are important for cessation of PV shedding in the gastrointestinal tract following an acute infection with wild type or vaccine-derived PV strains. We sought to produce IgA monoclonal antibodies (mAbs) with PV neutralizing activity. We first performed de novo [...] Read more.
Poliovirus (PV)-specific intestinal IgAs are important for cessation of PV shedding in the gastrointestinal tract following an acute infection with wild type or vaccine-derived PV strains. We sought to produce IgA monoclonal antibodies (mAbs) with PV neutralizing activity. We first performed de novo IgA discovery from primary human B cells using a hybridoma method that allows assessment of mAb binding and expression on the hybridoma surface: On-Cell mAb Screening (OCMS™). Six IgA1 mAbs were cloned by this method; three potently neutralized type 3 Sabin and wt PV strains. The hybridoma mAbs were heterogeneous, expressed in monomeric, dimeric, and aberrant forms. We also used recombinant methods to convert two high-potency anti-PV IgG mAbs into dimeric IgA1 and IgA2 mAbs. Isotype switching did not substantially change their neutralization activities. To purify the recombinant mAbs, Protein L binding was used, and one of the mAbs required a single amino acid substitution in its κ LC in order to enable protein L binding. Lastly, we used OCMS to assess IgA expression on the surface of hybridomas and transiently transfected, adherent cells. These studies have generated potent anti-PV IgA mAbs, for use in animal models, as well as additional tools for the discovery and production of human IgA mAbs. Full article
(This article belongs to the Special Issue Development of Therapeutic Antibodies against Toxins and Pathogens)
Show Figures

Figure 1

10 pages, 890 KiB  
Article
Equal Neutralization Potency of Antibodies Raised against Abrin Subunits
Antibodies 2020, 9(1), 4; https://doi.org/10.3390/antib9010004 - 06 Feb 2020
Cited by 4 | Viewed by 3398
Abstract
Abrin and ricin are potent AB toxins, which are considered biological threats. To date, there are no approved treatments against abrin or ricin intoxications. Previously, we showed that the administration of polyclonal anti-abrin antibodies to mice that were intranasally exposed to abrin, even [...] Read more.
Abrin and ricin are potent AB toxins, which are considered biological threats. To date, there are no approved treatments against abrin or ricin intoxications. Previously, we showed that the administration of polyclonal anti-abrin antibodies to mice that were intranasally exposed to abrin, even very late post-exposure, conferred an exceedingly high-level of protection, while following ricin intoxication, similar treatment with anti-ricin antibodies resulted in negligible survival rates. To probe this unexpected difference in protection ability, we first examined whether the efficient anti-abrin-induced protection was due to neutralization of the A-subunit responsible for the catalytic effect, or of the B-subunit, which enables binding/internalization, by evaluating the protection conferred by antibodies directed against one of the two subunits. To this end, we generated and immunized rabbits with chimeric toxins containing a single abrin subunit, AabrinBricin in which abrin A-subunit was linked to ricin B-subunit, and AricinBabrin in which ricin A-subunit is linked to abrin B-subunit. Here, we show that antibodies raised against either AabrinBricin or AricinBabrin conferred exceptionally high protection levels to mice following intranasal exposure to a a lethal dose of abrin, suggesting that the high level of protection conferred by anti-abrin antibodies is not related to the neutralization of a particular subunit. Full article
(This article belongs to the Special Issue Development of Therapeutic Antibodies against Toxins and Pathogens)
Show Figures

Figure 1

Review

Jump to: Research

13 pages, 1595 KiB  
Review
Immunoglobulin for Treating Bacterial Infections: One More Mechanism of Action
Antibodies 2019, 8(4), 52; https://doi.org/10.3390/antib8040052 - 03 Nov 2019
Cited by 15 | Viewed by 12893
Abstract
The mechanisms underlying the effects of immunoglobulins on bacterial infections are thought to involve bacterial cell lysis via complement activation, phagocytosis via bacterial opsonization, toxin neutralization, and antibody-dependent cell-mediated cytotoxicity. Nevertheless, recent advances in the study of the pathogenicity of Gram-negative bacteria have [...] Read more.
The mechanisms underlying the effects of immunoglobulins on bacterial infections are thought to involve bacterial cell lysis via complement activation, phagocytosis via bacterial opsonization, toxin neutralization, and antibody-dependent cell-mediated cytotoxicity. Nevertheless, recent advances in the study of the pathogenicity of Gram-negative bacteria have raised the possibility of an association between immunoglobulin and bacterial toxin secretion. Over time, new toxin secretion systems like the type III secretion system have been discovered in many pathogenic Gram-negative bacteria. With this system, the bacterial toxins are directly injected into the cytoplasm of the target cell through a special secretory apparatus without any exposure to the extracellular environment, and therefore with no opportunity for antibodies to neutralize the toxin. However, antibodies against the V-antigen, which is located on the needle-shaped tip of the bacterial secretion apparatus, can inhibit toxin translocation, thus raising the hope that the toxin may be susceptible to antibody targeting. Because multi-drug resistant bacteria are now prevalent, inhibiting this secretion mechanism is an attractive alternative or adjunctive therapy against lethal bacterial infections. Thus, it is not unreasonable to define the blocking effect of anti-V-antigen antibodies as the fifth mechanism for immunoglobulin action against bacterial infections. Full article
(This article belongs to the Special Issue Development of Therapeutic Antibodies against Toxins and Pathogens)
Show Figures

Figure 1

Back to TopTop