Special Issue "Toxin-Antibody Interactions"

Guest Editor
Dr. Nicholas J. Mantis
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA
Website: http://www.wadsworth.org/resnres/bios/mantis_pubs.html
E-Mail: nmantis@wadsworth.org
Phone: +1 518 473-7487
Fax: +1 518 402-4773

Dear Colleagues,

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
Guest Editor

Submission

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• antibody
• neutralization
• protection
• clearance
• vaccine
• therapeutics

Type of Paper: Article
Title: The MHC Class II Locus Differentially Influences the Humoral Immune Response to Bacillus anthracis Lethal Factor and Protective Antigen
Authors: Lori Garman ^1,2,†, Melissa L. Nguyen ^1,2,†, Philip M. Cox ¹, Jonathan Hunt ^1,2, Judith A. James ^1,2 and A. Darise Farris ^1,2
Affiliations: ¹ Oklahoma Medical Research Foundation, 825 N.E. 13^th Street, Oklahoma City, OK 73104, USA
² Oklahoma University Health Science Center, 1100 N. Lindsay, Oklahoma City, OK 73104, USA
^† These authors contributed equally to this work.
Abstract: Anthrax Lethal Toxin consists of Protective Antigen (PA) and Lethal Factor (LF), and current vaccination strategies focus on eliciting antibodies to PA. We have previously demonstrated that in human vaccination, the response to PA can vary wildly, with some individuals retaining protective titers to PA years after vaccination and others never generating a response, even after many vaccinations. In addition, the response is often directed to non-neutralizing epitopes, arguing for the need for vaccines to be targeted toward specific epitopes. Variable vaccine responses may be, in part, due to genetic differences in individuals; in both anthrax and other vaccinations, MHC class II and other genes have been shown to play a role in immune response. Here, we investigated the relative contribution of MHCII versus non-MHC classs II genes in the humoral response to PA and LF immunization using three strains of inbred mice: A/J (H-2^k at the MHC class II locus), C57BL/6J (H-2^b), and B6.AK-H2^k (H-2^k). IgG antibody titers to LF were controlled primarily by the MHC class II locus, whereas IgG titers to PA were strongly influenced by non-MHC class II genetic background. Pooled sera were tested for reactivity to solid-phase overlapping decapeptides of full-length LF and PA to define fine specificity of the humoral response. By this method, specificity of reactivity to LF appeared to be controlled primarily through non-MHC class II genes; that is, a full 39% of all epitopes were found only in A/J mice or in only B6 and B6.AK-H2^k mice, while only 17% were MHC II-determined. Conversely, specificity of reactivity to PA was MHC II-dependent; 31% of epitopes were found in B6 mice alone or in both A/J and B6.AK-H2^K mice, while 19% were background dependent. Common epitopes, reactive in all strains, were found in both LF (17%) and PA (44%) responses. These results demonstrate MHC class II differentially influences humoral immune responses to LF and PA.