Evaluation of the AV7909 Anthrax Vaccine Toxicity in Sprague Dawley Rats Following Three Intramuscular Administrations.
Evaluation of the AV7909 Anthrax Vaccine Toxicity in Sprague Dawley Rats Following Three Intramuscular Administrations.
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DOI：
10.1177/10915818211031239
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发表时间：
2021-10
影响因子：
2.2
通讯作者：
Savransky V
中科院分区：
文献类型：
--
作者：
Rao VV;Godin CS;Lacy MJ;Inglefield JR;Park S;Blauth B;Reece JJ;Ionin B;Savransky V
AV 7909是一种正在开发的下一代炭疽疫苗，用于疑似或确诊炭疽杆菌暴露后的暴露后预防（PEP），与推荐的抗菌方案联合使用。AV 7909由FDA批准的BioThrax®疫苗（吸附炭疽疫苗; AVA）和免疫刺激性Toll样受体9（TLR 9）激动剂寡脱氧核苷酸（ODN）佐剂CPG 7909组成。本研究旨在评价雄性和雌性Sprague道利大鼠右大腿肌肉（股二头肌）重复肌内（IM）注射AV 7909的潜在全身和局部毒性。在第1、15和29天接种疫苗，评估动物的给药相关效应，随后为2周恢复期，以评价任何毒性效应的持续性或可逆性。基于临床观察、体重、体温、临床病理学和解剖病理学的评价，AV 7909疫苗未产生明显的全身毒性。在注射部位以及区域淋巴结和邻近组织中观察到坏死和炎症，与免疫刺激一致。抗B抗体。在用AV 7909疫苗处理的大鼠中检测到炭疽保护性抗原（PA），证实了该动物模型用于评估AV 7909的全身毒性的相关性。相反，接受盐水或可溶性CPG 7909单独给药的大鼠血清抗PA抗体呈阴性。总体而言，用AV 7909对Sprague道利大鼠进行三次IM免疫耐受良好，未诱导死亡或任何全身不良反应，并且未导致任何延迟毒性。
AV7909 is a next-generation anthrax vaccine under development for post-exposure prophylaxis (PEP) following suspected or confirmed Bacillus anthracis exposure, when administered in conjunction with the recommended antibacterial regimen. AV7909 consists of the FDA approved BioThrax® vaccine (Anthrax Vaccine Adsorbed; AVA) and an immunostimulatory Toll-like receptor 9 (TLR9) agonist oligodeoxynucleotide (ODN) adjuvant, CPG 7909. The purpose of this study was to evaluate the potential systemic and local toxicity of AV7909 when administered via repeat intramuscular (IM) injection to the right thigh muscle (biceps femoris) to male and female Sprague Dawley rats. The vaccine was administered on Days 1, 15 and 29 and the animals were assessed for treatment-related effects followed by a two-week recovery period to evaluate the persistence or reversibility of any toxic effects. The AV7909 vaccine produced no apparent systemic toxicity based on evaluation of clinical observations, body weights, body temperature, clinical pathology, and anatomic pathology. Necrosis and inflammation were observed at the injection sites as well as in regional lymph nodes and adjacent tissues and were consistent with immune stimulation. Antibodies against B. anthracis protective antigen (PA) were detected in rats treated with the AV7909 vaccine, confirming relevance of this animal model for the assessment of systemic toxicity of AV7909. In contrast, sera of rats that received saline or soluble CPG 7909 alone were negative for anti-PA antibodies. Overall, three IM immunizations of Sprague Dawley rats with AV7909 were well tolerated, did not induce mortality or any systemic adverse effects, and did not result in any delayed toxicity.
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影响因子：
3.7
作者：
Mullen GE;Ellis RD;Miura K;Malkin E;Nolan C;Hay M;Fay MP;Saul A;Zhu D;Rausch K;Moretz S;Zhou H;Long CA;Miller LH;Treanor J
通讯作者：
Treanor J
影响因子：
5.5
作者：
Mullen, Gregory E. D.;Aebig, Joan A.;Saul, Allan
通讯作者：
Saul, Allan
影响因子：
2.2
作者：
Li, Han;Soroka, Stephen D.;Quinn, Conrad P.
通讯作者：
Quinn, Conrad P.
影响因子：
5.5
作者：
Ondondo, Beatrice;Brennan, Caroline;Hanke, Tomag
通讯作者：
Hanke, Tomag
影响因子：
5.5
作者：
Qian, Feng;Rausch, Kelly M.;Mullen, Gregory E. D.
通讯作者：
Mullen, Gregory E. D.