A Monoclonal Immunoglobulin G Antibody Directed against an Immunodominant Linear Epitope on the Ricin A Chain Confers Systemic and Mucosal Immunity to Ricin
| العنوان: | A Monoclonal Immunoglobulin G Antibody Directed against an Immunodominant Linear Epitope on the Ricin A Chain Confers Systemic and Mucosal Immunity to Ricin |
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| المؤلفون: | Joanne M. O’Hara, Nicholas J. Mantis, Robert N. Brey, Lori M. Neal |
| المصدر: | Infection and Immunity. 78:552-561 |
| بيانات النشر: | American Society for Microbiology, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Models, Molecular, medicine.drug_class, Immunology, Ricin, Monoclonal antibody, Microbiology, Immunoglobulin G, Epitope, Mice, Open Reading Frames, chemistry.chemical_compound, Immunotoxin, Chlorocebus aethiops, medicine, Animals, Immunity, Mucosal, Vero Cells, biology, Linear epitope, Immunodominant Epitopes, Antibodies, Monoclonal, Virology, carbohydrates (lipids), Infectious Diseases, chemistry, Polyclonal antibodies, Microbial Immunity and Vaccines, biology.protein, Female, Parasitology, Antitoxin |
| الوصف: | Due to the potential use of ricin and other fast-acting toxins as agents of bioterrorism, there is an urgent need for the development of safe and effective antitoxin vaccines. A candidate ricin subunit vaccine (RiVax) consisting of a recombinant attenuated enzymatic A chain (RTA) has been shown to elicit protective antitoxin antibodies in mice and rabbits and is currently being tested in phase I human clinical trials. However, evaluation of the efficacy of this vaccine for humans is difficult for a number of reasons, including the fact that the key neutralizing B-cell epitopes on RTA have not been fully defined. Castelletti and colleagues (Clin. Exp. Immunol.136:365-372, 2004) recently identified a linear epitope on RTA, spanning residues L161 to I175, as a primary target of serum antibodies derived from humans who had been treated with ricin immunotoxin. While affinity-purified polyclonal IgG antibodies against this region of RTA were capable of neutralizing ricinin vitro, their capacity to confer protection against ricin challengein vivowas not determined. In this report, we describe the production and characterization of GD12, a murine monoclonal IgG1 antibody specifically directed against residues 163 to 174 (TLARSFIICIQM) of RTA. GD12 bound ricin holotoxin with high affinity (KD[dissociation constant], 2.9 × 10−9M) and neutralized it with a 50% inhibitory concentration of ∼0.25 μg/ml, as determined by a Vero cell-based cytotoxicity assay. Passive administration of GD12 was sufficient to protect BALB/c mice against intraperitoneal and intragastric ricin challenges. These data are important in terms of vaccine development, since they firmly establish that preexisting serum antibodies directed against residues 161 to 175 on RTA are sufficient to confer both systemic and mucosal immunity to ricin. The potential of GD12 to serve as a therapeutic following ricin challenge was not explored in this study. |
| تدمد: | 1098-5522 0019-9567 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00b140bdb65438aba2ec5b1c25238480 https://doi.org/10.1128/iai.00796-09 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....00b140bdb65438aba2ec5b1c25238480 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985522 00199567 |
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