The AV7909 vaccine, consists of the Anthrax Vaccine Adsorbed (AVA) bulk drug substance and the immunostimulatory Toll‐like receptor 9 agonist oligodeoxynucleotide adjuvant CPG 7909. The purpose of this research was to evaluate the potential maternal, reproductive, and developmental toxicity of AV7909 in rats to support licensure for use in women of childbearing potential. Groups of first generation (F₀) female Sprague Dawley rats were dosed by intramuscular injection with water for injection, adjuvant or AV7909 at a volume of 0.5 ml/dose. Each rat received three vaccinations: 14 days prior to start of the mating period, on the first day of the mating period and on gestation day (GD) 7. There was no maternal mortality. Body weights, weight gain, and food consumption were comparable between groups. Findings in F₀ females were limited to transient injection site edema and nodules consistent with immunostimulatory effects of the vaccine and adjuvant. Administration of AV7909 did not affect mating, fertility, pregnancy, embryo‐fetal viability, growth, or morphologic development, parturition, maternal care of offspring or postnatal survival, growth, or development. There was no evidence of systemic inflammation in pregnant rats, based on evaluation of serum concentrations of the acute phase proteins alpha‐2‐macroglobulin and alpha‐1‐acid glycoprotein on GD 21. Anthrax lethal toxin‐neutralizing antibodies were detected in AV7909‐vaccinated F₀ females. The antibodies were also detected in the sera of fetuses and F₁ pups. Exposure of the fetuses and pups to maternally derived anthrax lethal toxin‐neutralizing antibodies was not associated with developmental toxicity.

中文翻译：

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AV7909炭疽候选疫苗在大鼠体内的发育和生殖安全性评价

AV7909 疫苗由炭疽疫苗吸附 (AVA) 原料药和免疫刺激性 Toll 样受体 9 激动剂寡脱氧核苷酸佐剂 CPG 7909 组成。本研究的目的是评估 AV7909 对母体、生殖和发育的潜在毒性大鼠支持许可用于育龄妇女。第一代(F ₀ )雌性Sprague Dawley大鼠组通过肌内注射注射用水、佐剂或AV7909以0.5ml/剂量的体积给药。每只大鼠接受三种疫苗接种：交配期开始前 14 天、交配期第一天和妊娠第 7 天。没有孕产妇死亡。体重、体重增加和食物消耗在各组之间具有可比性。在 F 中的发现_{0 只}雌性被限制为与疫苗和佐剂的免疫刺激作用一致的短暂注射部位水肿和结节。AV7909 的施用不影响交配、生育力、妊娠、胚胎-胎儿活力、生长或形态发育、分娩、后代的母体护理或产后存活、生长或发育。根据对 GD 21 急性期蛋白 α-2-巨球蛋白和 α-1-酸性糖蛋白的血清浓度的评估，没有妊娠大鼠全身炎症的证据。在接种 AV7909 的疫苗中检测到炭疽致死毒素中和抗体F ₀女性。在胎儿和 F ₁的血清中也检测到抗体幼崽。胎儿和幼崽暴露于母源性炭疽致死毒素中和抗体与发育毒性无关。