Thrombus imaging with an I-123-labeled F(ab')2 fragment of an anti-human fibrin monoclonal antibody in a rabbit model.

Radiology ◽  
1989 ◽  
Vol 171 (1) ◽  
pp. 223-226 ◽  
Author(s):  
Y Hashimoto ◽  
J M Stassen ◽  
B Leclef ◽  
M De Roo ◽  
A Vandecruys ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Rabbit Model ◽  
Thrombus Imaging

Contribution of LFA-1 and Mac-1 to CD18-dependent neutrophil emigration in a neonatal rabbit model

1996 ◽  
Vol 80 (6) ◽  
pp. 1984-1992 ◽  
Author(s):  
J. M. Graf ◽  
C. W. Smith ◽  
M. M. Mariscalco
Keyword(s):  
Monoclonal Antibody ◽  
Polymorphonuclear Leukocytes ◽  
Rabbit Model ◽  
Transendothelial Migration ◽  
Peritoneal Exudate ◽  
Adult Rabbit ◽  
Primary Mechanism ◽  
Phosphate Buffered Saline

Human neonatal polymorphonuclear leukocytes (PMNs) exhibit decreased mobility, adherence, and transendothelial migration in vitro compared with adult PMNs. These deficits, in part, are due to functional and quantitative defects in neonatal Mac-1 (CD11b/CD18), whereas LFA-1 (CD11a/CD18) function is similar to that found in adults (D.C.Anderson, O.Abbassi, T.K.Kishimoto, J.M.Koenig, L.V.McIntire, and C.W.Smith, J.Immunol. 146: 3372-3379, 1991; C. W. Smith, T. K. Kishimoto, O. Abbassi, B.J.Hughes, R.Rothlein, L.V.McIntire, E.Butcher, and D.C. Anderson, J. Clin. Invest. 87: 609-618, 1991). We tested the hypothesis that the primary mechanism for the neonatal PMN CD18-dependent emigration in vivo is due to LFA-1. Neutrophils from 1-day-old rabbit pups had 32 and 60% of adult rabbit levels of CD11a and CD11b, respectively. Rabbit pups or adult rabbits received the monoclonal antibody (MAb) R7.1 (anti-CD11a) or R15.7 (anti-CD18) or the vehicle phosphate-buffered saline (PBS) before the instillation of intraperitoneal thioglycollate. Six hours later peritoneal exudate was collected. The administration of MAbs R7.1 and R15.7 in adult animals resulted in 60 and 83% inhibition of leukocyte emigration, respectively, compared with PBS-treated animals (P < 0.01). In neonatal animals, R7.1 and R15.7 inhibited leukocyte peritoneal accumulation to the same extent (50 and 60%, respectively) compared with PBS-treated animals (P < 0.01). Adult animals were also treated with the anti-CD11b MAb 198. MAb 198 decreased emigration by 25%, although this was not significant compared with PBS-treated animals. We conclude that although neonatal animals have significantly less neutrophil CD11a, the diminished levels did not contribute to a reduced ability to emigrate to the peritoneum and, like adult animals, neonatal animals primarily utilize LFA-1 for accumulation in this model. The contribution of Mac-1 to neonatal leukocyte emigration remains uncertain.

scholarly journals Human Monoclonal Antibody AVP-21D9 to Protective Antigen Reduces Dissemination of the Bacillus anthracis Ames Strain from the Lungs in a Rabbit Model

2007 ◽  
Vol 75 (7) ◽  
pp. 3414-3424 ◽  
Author(s):  
Johnny W. Peterson ◽  
Jason E. Comer ◽  
Wallace B. Baze ◽  
David M. Noffsinger ◽  
Autumn Wenglikowski ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Human Monoclonal Antibody ◽  
Rabbit Model ◽  
Concomitant Treatment ◽  
Dependent Manner ◽  
Lethal Challenge ◽  
Tissue Sections ◽  
Inhalation Anthrax

ABSTRACT Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some naïve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.

scholarly journals Establishment of a New Zealand White Rabbit Model for Lethal Toxin (LT) Challenge and Efficacy of Monoclonal Antibody 5E11 in the LT-Challenged Rabbit Model

Toxins ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 289 ◽  
Author(s):  
Duanyang Zhang ◽  
Weicen Liu ◽  
Zhonghua Wen ◽  
Bing Li ◽  
Shuling Liu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Protective Antigen ◽  
Lethal Dose ◽  
Rabbit Model ◽  
Zealand White Rabbit ◽  
Lethal Toxin ◽  
Anthrax Spores ◽  
Level 3 ◽  
Anthrax Protective Antigen ◽  
Biosafety Level

Anthrax caused by Bacillus anthracis is a lethal infectious disease, especially when inhaled, and the mortality rate approaches 100% without treatment. The anthrax antitoxin monoclonal antibody (MAb) 5E11 is a humanized antibody that targets the anthrax protective antigen (PA). The efficacy of 5E11 needs proper animal models. However, anthrax spores are extremely dangerous, so experiments must be conducted under Biosafety Level 3 conditions. Considering the critical effects of lethal toxin (LT) on hosts during infection, we report the establishment of a LT-challenged rabbit model, which caused 100% mortality with a dose of 2 mg PA + 1 mg LF, while a 4 mg PA + 2 mg LF challenge could limit death to within three days. Then, we evaluated 5E11 efficacy against LT. A prophylactic study showed that the i.v. administration of 40 mg/kg 5E11 four days before lethal dose LT challenge could lead to 100% survival. In therapeutic studies, the i.v. administration of 40 mg/kg 5E11 10 min after lethal dose LT challenge could provide complete protection. Overall, we developed a new LT-challenged rabbit model, and our results indicate that 5E11 shows potential for the clinical application in anthrax treatment.

212 Thrombus imaging with an antifibrin monoclonal antibody (MoAb)

1988 ◽  
Vol 2 ◽  
pp. 89
Author(s):  
M.N.J.M. Wasser ◽  
R.I.J. Feitsma ◽  
E.K.J. Pauwels ◽  
W. Nieuwenhuizen
Keyword(s):  
Monoclonal Antibody ◽  
Thrombus Imaging

scholarly journals Efficacy of ETI-204 Monoclonal Antibody as an Adjunct Therapy in a New Zealand White Rabbit Partial Survival Model for Inhalational Anthrax

2015 ◽  
Vol 59 (4) ◽  
pp. 2206-2214 ◽  
Author(s):  
Bethany Biron ◽  
Katie Beck ◽  
David Dyer ◽  
Marc Mattix ◽  
Nancy Twenhafel ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
New Zealand ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Rabbit Model ◽  
Zealand White Rabbit ◽  
Adjunct Therapy ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Effective Therapeutic Strategy

ABSTRACTInhalational anthrax is characterized by extensive bacteremia and toxemia as well as nonspecific to mild flu-like symptoms, until the onset of hypotension, shock, and mortality. Without treatment, the mortality rate approaches 100%. Antibiotic treatment is not always effective, and alternative treatments are needed, such as monotherapy for antibiotic-resistant inhalational anthrax or as an adjunct therapy in combination with antibiotics. TheBacillus anthracisantitoxin monoclonal antibody (MAb) ETI-204 is a high-affinity chimeric deimmunized antibody which targets the anthrax toxin protective antigen (PA). In this study, a partial protection New Zealand White (NZW) rabbit model was used to evaluate the protective efficacy of the adjunct therapy with the MAb. Following detection of PA in the blood, NZW rabbits were administered either an antibiotic (doxycycline) alone or the antibiotic in conjunction with ETI-204. Survival was evaluated to compare the efficacy of the combination adjunct therapy with that of an antibiotic alone in treating inhalational anthrax. Overall, the results from this study indicate that a subtherapeutic regimen consisting of an antibiotic in combination with an anti-PA MAb results in increased survival compared to the antibiotic alone and would provide an effective therapeutic strategy against symptomatic anthrax in nonvaccinated individuals.

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