Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax
| Autor: | Hans Westra, E. Diane Williamson, Chris S. LeButt, Helen C. Flick-Smith, Han Li, Les Baillie, Alfred J. Mateczun, Conrad P. Quinn, Stanley Goldman, Mark T. Albrecht, Darrell R. Galloway, Herman Groen |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
RM
medicine.drug_class Anthrax toxin Immunology Bacterial Toxins VACCINE TOXIN Biology Monoclonal antibody Microbiology Immunoglobulin G Anthrax Inhibitory Concentration 50 Mice Antigen Immunity medicine Animals Humans AFFINITY Antigens Bacterial Anthrax vaccines Hybridomas IDENTIFICATION GUINEA-PIGS Immunization Passive Antibodies Monoclonal biology.organism_classification Virology Antibodies Bacterial Survival Analysis RABBITS Bacillus anthracis Infectious Diseases INHALATION ANTHRAX Microbial Immunity and Vaccines biology.protein Parasitology Female Antitoxins Antibody CHALLENGE RECEPTOR-BINDING RESPONSES |
| Zdroj: | Infection and Immunity, 75(11), 5425-5433. AMER SOC MICROBIOLOGY |
| ISSN: | 0019-9567 |
| Popis: | The unpredictable nature of bioterrorism and the absence of real-time detection systems have highlighted the need for an efficient postexposure therapy forBacillus anthracisinfection. One approach is passive immunization through the administration of antibodies that mitigate the biological action of anthrax toxin. We isolated and characterized two protective fully human monoclonal antibodies with specificity for protective antigen (PA) and lethal factor (LF). These antibodies, designated IQNPA (anti-PA) and IQNLF (anti-LF), were developed as hybridomas from individuals immunized with licensed anthrax vaccine. The effective concentration of IQNPA that neutralized 50% of the toxin in anthrax toxin neutralization assays was 0.3 nM, while 0.1 nM IQNLF neutralized the same amount of toxin. When combined, the antibodies had additive neutralization efficacy. IQNPA binds to domain IV of PA containing the host cell receptor binding site, while IQNLF recognizes domain I containing the PA binding region in LF. A single 180-μg dose of either antibody given to A/J mice 2.5 h before challenge conferred 100% protection against a lethal intraperitoneal spore challenge with 24 50% lethal doses [LD50s] ofB. anthracisSterne and against rechallenge on day 20 with a more aggressive challenge dose of 41 LD50s. Mice treated with either antibody and infected withB. anthracisSterne developed detectable murine anti-PA and anti-LF immunoglobulin G antibody responses by day 17 that were dependent on which antibody the mice had received. Based on these results, IQNPA and IQNLF act independently during prophylactic anthrax treatment and do not interfere with the establishment of endogenous immunity. |
| Databáze: | OpenAIRE |
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