Next Article in Journal
Therapeutic Potential of Cholera Toxin B Subunit for the Treatment of Inflammatory Diseases of the Mucosa
Next Article in Special Issue
Erratum: Differences in Ribosome Binding and Sarcin/Ricin Loop Depurination by Shiga and Ricin Holotoxins. Toxins 2017, 9, 133
Previous Article in Journal
Correction: S. Vogelgsang et al. Fusarium Mycotoxins in Swiss Wheat: A Survey of Growers’ Samples between 2007 and 2014 Shows Strong Year and Minor Geographic Effects. Toxins 2017, 9, 246
Previous Article in Special Issue
Microvesicle Involvement in Shiga Toxin-Associated Infection
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessFeature PaperArticle
Toxins 2017, 9(12), 378; https://doi.org/10.3390/toxins9120378

A Supercluster of Neutralizing Epitopes at the Interface of Ricin’s Enzymatic (RTA) and Binding (RTB) Subunits

1
Department of Biomedical Sciences, University at Albany School of Public Health, Albany, NY 12201, USA
2
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Julien Barbier and Daniel Gillet
Received: 5 September 2017 / Revised: 10 November 2017 / Accepted: 18 November 2017 / Published: 23 November 2017
(This article belongs to the Special Issue Ribosome Inactivating Toxins)
View Full-Text   |   Download PDF [6199 KB, uploaded 23 November 2017]   |  

Abstract

As part of an effort to engineer ricin antitoxins and immunotherapies, we previously produced and characterized a collection of phage-displayed, heavy chain-only antibodies (VHHs) from alpacas that had been immunized with ricin antigens. In our initial screens, we identified nine VHHs directed against ricin toxin’s binding subunit (RTB), but only one, JIZ-B7, had toxin-neutralizing activity. Linking JIZ-B7 to different VHHs against ricin’s enzymatic subunit (RTA) resulted in several bispecific antibodies with potent toxin-neutralizing activity in vitro and in vivo. JIZ-B7 may therefore be an integral component of a future VHH-based neutralizing agent (VNA) for ricin toxin. In this study, we now localize, using competitive ELISA, JIZ-B7’s epitope to a region of RTB’s domain 2 sandwiched between the high-affinity galactose/N-acetylgalactosamine (Gal/GalNAc)-binding site and the boundary of a neutralizing hotspot on RTA known as cluster II. Analysis of additional RTB (n = 8)- and holotoxin (n = 4)-specific VHHs from a recent series of screens identified a “supercluster” of neutralizing epitopes at the RTA-RTB interface. Among the VHHs tested, toxin-neutralizing activity was most closely associated with epitope proximity to RTA, and not interference with RTB’s ability to engage Gal/GalNAc receptors. We conclude that JIZ-B7 is representative of a larger group of potent toxin-neutralizing antibodies, possibly including many described in the literature dating back several decades, that recognize tertiary and possibly quaternary epitopes located at the RTA-RTB interface and that target a region of vulnerability on ricin toxin. View Full-Text
Keywords: ricin; antibody; neutralizing; epitope ricin; antibody; neutralizing; epitope
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Poon, A.Y.; Vance, D.J.; Rong, Y.; Ehrbar, D.; Mantis, N.J. A Supercluster of Neutralizing Epitopes at the Interface of Ricin’s Enzymatic (RTA) and Binding (RTB) Subunits. Toxins 2017, 9, 378.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top