Special Issue "Toxin-Antibody Interactions"
A special issue of Toxins (ISSN 2072-6651).
Deadline for manuscript submissions: 31 January 2014
Dr. Nicholas J. Mantis
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA
Phone: +1 518 473-7487
Fax: +1 518 402-4773
Interests: plant and bacterial protein toxins; neutralizing antibodies; vaccines; mucosal tissues; animal models; small molecule inhibitors
Antibodies are remarkable in their ability to inactivate even the most potent plant and microbial toxins, including botulinum, tetanus, diphtheria, anthrax and ricin toxins. While this fact has been recognized for more than a century, surprisingly little is known about the molecular mechanisms by which antibodies actually neutralize toxins. Indeed, historically, there has been little incentive to investigate the nature of toxin-antibody interactions because of the success of so many toxin vaccines and therapies. However, this has changed in the past decade with the global demand in the public health and biodefense sectors for new generation antibody-based countermeasures that are safer and more effective. With the surge in new research, it is now becoming increasingly apparent that the interactions between toxins-antibodies are as complex, sophisticated and interesting as the toxins themselves.
The goal of this special issue of Toxins is to provide a state-of-the-art look into the diverse mechanisms by which antibodies neutralize toxins and insights into how understanding these interactions will have applications for next generation vaccines and therapeutics.
Dr. Nicholas J. Mantis
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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.
Toxins 2012, 4(6), 430-454; doi:10.3390/toxins4060430
Received: 29 April 2012; in revised form: 6 June 2012 / Accepted: 7 June 2012 / Published: 11 June 2012| Download PDF Full-text (526 KB) | Download XML Full-text
Article: Humanized-Single Domain Antibodies (VH/VHH) that Bound Specifically to Naja kaouthia Phospholipase A2 and Neutralized the Enzymatic Activity
Toxins 2012, 4(7), 554-567; doi:10.3390/toxins4070554
Received: 19 June 2012; in revised form: 26 June 2012 / Accepted: 6 July 2012 / Published: 19 July 2012| Download PDF Full-text (1125 KB) | Download XML Full-text | Supplementary Files
Article: Interaction between Shiga Toxin and Monoclonal Antibodies: Binding Characteristics and in Vitro Neutralizing Abilities
Toxins 2012, 4(9), 729-747; doi:10.3390/toxins4090729
Received: 28 August 2012; in revised form: 17 September 2012 / Accepted: 17 September 2012 / Published: 18 September 2012| Download PDF Full-text (1379 KB) | Download XML Full-text
Article: MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen
Toxins 2012, 4(12), 1451-1467; doi:10.3390/toxins4121451
Received: 22 August 2012; in revised form: 16 November 2012 / Accepted: 28 November 2012 / Published: 5 December 2012| Download PDF Full-text (330 KB) | Download XML Full-text
Toxins 2012, 4(12), 1565-1581; doi:10.3390/toxins4121565
Received: 22 November 2012; in revised form: 13 December 2012 / Accepted: 13 December 2012 / Published: 19 December 2012| Download PDF Full-text (562 KB) | Download XML Full-text
Article: Cloning and Characterization of a Hybridoma Secreting a 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-Specific Monoclonal Antibody and Recombinant F(ab)
Toxins 2013, 5(3), 568-589; doi:10.3390/toxins5030568
Received: 9 January 2013; in revised form: 28 February 2013 / Accepted: 5 March 2013 / Published: 19 March 2013| Download PDF Full-text (785 KB) | Download XML Full-text
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Engineering Toxin-Neutralizing Antibody Fragments and Their Therapeutic Potential
Authors: L.M. Alvarenga, N. Aubrey, P. Billiald and Julien Muzard *
Affiliation: Bioinformatics Department, Conservatoire National des Arts & Metiers, 75003 Paris, France; E-Mail: julien dot muzard at cnam dot fr
Abstract: Serum therapy remains the only specific treatment against envenoming but antivenoms are still prepared by proteolytic fragmentation of polyclonal antibodies isolated from hyperimmunized horse serum. Most of these antivenoms are efficient, but their production remains tedious and their use may be associated to adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives, and constitute a source of still unexploited biomolecules capable to neutralize venoms. This review will be a walk through the technologies that have recently been applied to design and develop novel antibody formats with well-characterized properties (e.g., homogeneity, specific anti-toxin activity and possible clinical safety).
Title: Role of Antibody Fc in Protection from Ricin Toxicosis
Authors: A. Das 1,2, K. Song 1, G. A. Maresh 1, J. Berry 3 and S. H. Pincus 1,4
Affiliations: 1 Children's Hospital New Orleans, LA, USA; E-Mail: firstname.lastname@example.org (S.H.P.)
2 Tulane University, New Orleans, LA, USA
3 Cangene, Winnipeg, Canada
4 Departments of Pediatrics and Microbiology, LSU Health Sciences Center, New Orleans, LA, USA
Abstract: Studies with Fc receptor knockout mice have been interpreted to indicate that the antibody Fc region is critical for protection from toxin effects. Yet polyclonal anti-toxin antibodies are sold as Fab/F(ab)'2 "despeciated" preparations, with the purported advantage of lower immunogenicity. To address the role of antibody Fc regions, we have compared intact and Fab preparations of monoclonal and polyclonal antibodies to ricin, a well characterized model system with direct anti-bioterrorist applications. They have been studied in vitro using FcR- and FcR+ cells and in vivo using a systemic challenge model. In vitro analyses include ricin-binding assays, flow cytometry, quantitative confocal microscopy, and ricin neutralization assays.
Type of Paper: Review
Title: Towards Clinical Applications of Anti-endotoxin Antibodies: A Re-appraisal of the Disconnect
Authors: James C. Hurley
Affiliation: Rural Health Academic Centre, Melbourne Medical School, The University of Melbourne, Austria; E-Mail: email@example.com (H.C.H.)
Abstract: Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all gram negative (GN) bacteria. It would be expected that anti-endotoxemia therapies would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of therapy using anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trails of antibody based anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this literature is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine the important factors that may explain this disconnect. These factors include the frequency and types of GN bacteremias and the underlying mortality risk in the study population. Moreover, these old studies warrant a re-interpretation in light of more recent advances in the understanding of the structure-function relationship of endotoxin.
Type of Paper: Review
Title: Recent Developments in Antibody-Based Assays for the Detection of Bacterial Toxins
Authors: Kui Zhu, Richard Dietrich, Andrea Didier, Dominik Doyscher and Erwin Märtlbauer,
Affiliation: Institute of Food Safety, Department of Veterinary Sciences, Ludwig-Maximilians-University Munich, Oberschleißheim, 85764, Germany;
Abstract: Considering the urgent demand for rapid and accurate determination of bacterial toxins and the recent promising developments in nanotechnology and microfluidics, this review summarizes new achievements of the past five years. Firstly, bacterial toxins will be categorized according to their antibody binding properties into low and high molecular weight compounds. Secondly, the types of antibodies and new techniques for producing antibodies are discussed, including poly- and monoclonal antibodies, single-chain variable fragments (scFv) as well as heavy-chain and recombinant antibodies. Thirdly, the use of different nanomaterials, such as gold nanoparticles (AuNPs), magnetic beads, carbon nanomaterials (graphene and carbon nanotube), quantum dots (QDs) and nanoclusters (AgNCs and AuNCs), for labeling antibodies and toxins or for readout techniques will be summarized. Fourthly, microscale analysis or minimized devices, for example microfluidics or lab on a chip (LOC), which have attracted increasing attention in combination with immunoassays for robust detection or point-of-care testing (POCT), will be reviewed. Finally, some new materials and analytical strategies, which might be promising for analyzing toxins in the near future, will be shortly introduced.
Type of Paper: Article
Title: Active Immunity Induced by Passive IgG Post-Exposure Protection against Ricin
Authors: Charles Chen Hu, Junfei Yin, Damon Chau, John W. Cherwonogrodzky and Wei-Gang Hu *
Affiliation: Defence Research and Development Canada-Suffield, Box 4000, Station Main, Medicine Hat, Alberta, T1A 8K6, Canada; E-Mail: firstname.lastname@example.org (W.-G.H.); Tel.: +1-403-544-4674; Fax: +1-403-544-3388
Abstract: Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and its F(ab’)2 fragment from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. The results showed that similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab’)2 when compared at the same molar concentration. In a murine ricin intoxication model, both IgG and F(ab’)2 could rescue 100% of the mice by one dose (30 nmol) administration of antibodies 1 hr after 5 × LD50 ricin challenge. Nine days later, when the rescued mice received a second ricin challenge (5 × LD50), only the IgG-treated mice survived; the F(ab’)2-treated mice did not. The experimental design excluded the possibility of residual goat IgG responsible for the protection against the second ricin challenge. Results confirmed that the active immunity against ricin in mice was induced quickly following the passive delivery of a single dose of goat IgG post-exposure. Furthermore, it was demonstrated that the induced active immunity against ricin in mice lasted at least 5 months. Therefore, although passive IgG therapy might be an ideal approach to provide immediate protection to the victim after ricin exposure, it may also elicit an active immunity against ricin intoxication that subsequently results in long term protection.
Keywords: active immunity; F(ab’)2; IgG; passive antibody therapy; post-exposure; ricin
Last update: 9 December 2013