Efficacy of ETI-204 Monoclonal Antibody as an Adjunct Therapy in a New Zealand White Rabbit Partial Survival Model for Inhalational Anthrax
Efficacy of ETI-204 Monoclonal Antibody as an Adjunct Therapy in a New Zealand White Rabbit Partial Survival Model for Inhalational Anthrax
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DOI：
10.1128/aac.04593-14
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发表时间：
2015-04-01
影响因子：
4.9
通讯作者：
Nalca, Aysegul
中科院分区：
文献类型：
--
作者：
Biron, Bethany;Beck, Katie;Nalca, Aysegul
吸入性炭疽的特点是广泛的菌血症和毒血症以及非特异性至轻度流感样症状，直至出现低血压、休克和死亡。如果不进行治疗，死亡率接近100%。抗生素治疗并不总是有效，需要替代治疗，例如针对抗生素耐药性吸入性炭疽的单一疗法或与抗生素联合使用的辅助疗法。炭疽杆菌抗毒素单克隆抗体 (MAb) ETI-204 是一种高亲和力嵌合去免疫抗体，靶向炭疽毒素保护性抗原 (PA)。在本研究中，使用部分保护新西兰白兔（NZW）模型来评估单克隆抗体辅助治疗的保护功效。检测到血液中的 PA 后，对 NZW 兔单独施用抗生素（多西环素）或将抗生素与 ETI-204 联合施用。评估生存率，以比较联合辅助疗法与单独使用抗生素治疗吸入性炭疽的疗效。总体而言，这项研究的结果表明，与单独使用抗生素相比，由抗生素与抗 PA MAb 组合组成的亚治疗方案可提高生存率，并且将为未接种疫苗的个体提供针对症状性炭疽的有效治疗策略。
Inhalational 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. The Bacillus anthracis antitoxin 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.