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Immunogenicity and Protective Efficacy of Recombinant Protective Antigen Anthrax Vaccine (GC1109) in A/J Mice Model
Institution:1. Department of Medicine, Baylor College of Medicine, Houston, TX, United States;2. Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, United States;3. Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States;4. University of Iowa College of Medicine, Iowa City, IA, United States;5. Saint Louis University School of Medicine, St. Louis, MO, United States;6. Emmes Corporation, Rockville, MD, United States;7. BiondVax Pharmaceuticals, Ltd., Jerusalem, Israel;8. Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States;1. Instituto Biomédico, Universidade Federal Fluminense, Alameda Barros Terra, s/n. São Domingos, Niterói, RJ 24020-150, Brazil;2. Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro. Av. Carlos Chagas Filho, 373 - bloco I, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-902, Brazil;1. College of Chemistry and Material Sciences, School of Life Sciences, Heilongjiang University, Harbin, Heilongjiang 150080, China;2. Institute of Nanobiomaterials and Immunology, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Life Sciences, Taizhou University, Taizhou 318000, China;1. George Washington University Hospital, Department of Obstetrics and Gynecology, 900 23rd ST NW, Washington, DC 20037, United States;2. George Washington University, School of Medicine and Health Sciences, 2300 I St NW, Washington, DC 20052, United States;3. Sarasota Memorial Hospital, 1700 S Tamiami Trail, Sarasota, FL 34239, United States;1. Section of Hematology, Department of Medicine, Faculty of Medicine and Health, Örebro University, SE 70185 Örebro, Sweden;2. Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden;3. Unit of Hematology, Department of Medicine, Karolinska Institute, Stockholm, Sweden;4. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden;5. School of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE 70185 Örebro, Sweden;1. University Francisco Marroquin School of Medicine, Guatemala City, Guatemala;2. Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA;3. Center for Global Health, Colorado School of Public Health, Aurora, CO, USA;4. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA;5. Department of Infectious Diseases and Epidemiology, Children’s Hospital Colorado, Aurora, CO, USA
Abstract:A recombinant protective antigen anthrax vaccine (GC1109) is being developed as a new-generation vaccine by the Korea Disease Control and Prevention Agency. In accordance with the ongoing step 2 of phase II clinical trials, the immunogenicity and protective efficacy of the booster dose of GC1109 were evaluated in A/J mice after 3 serial vaccinations at 4-week intervals. The results indicated that the booster dose significantly increased the production of anti-protective antigen (PA) IgG and toxin-neutralizing antibody (TNA) compared with those of the group without booster. An enhanced protective effect of the booster dose was not observed because the TNA titers of the group without booster were high enough to confer protection against spore challenge. Additionally, the correlation between TNA titers and probability of survival was determined for calculating the threshold TNA titer levels associated with protection. The threshold 50 % neutralization factor (NF50) of TNA showing 70 % probability of protection was 0.21 in A/J mice with 1,200 LD50 Sterne spores challenge. These results indicate that GC1109 is a promising candidate as a new-generation anthrax vaccine and that a booster dose might provide enhanced protection by producing toxin-neutralizing antibodies.
Keywords:Anthrax vaccine  GC1109  Toxin neutralization assay  Survival  A/J mice
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