Lack of effects on female fertility and prenatal and postnatal offspring development in rats with BNT162b2, a mRNA-based COVID-19 vaccine.
Lack of effects on female fertility and prenatal and postnatal offspring development in rats with BNT162b2, a mRNA-based COVID-19 vaccine.
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DOI：
10.1016/j.reprotox.2021.05.007
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Lindemann C
中科院分区：
文献类型：
--
作者：
Bowman CJ;Bouressam M;Campion SN;Cappon GD;Catlin NR;Cutler MW;Diekmann J;Rohde CM;Sellers RS;Lindemann C
BNT162b2 是一种为预防 2019 年冠状病毒病 (COVID-19) 而开发的疫苗。 BNT162b2 是一种脂质纳米颗粒配制的核苷修饰信使 RNA (mRNA)，编码锁定在其预融合构象的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 刺突蛋白。根据国际监管指南，在大鼠中进行了发育和生殖毒性研究。在交配前 21 天和 14 天以及妊娠第 9 天和 20 天，对 44 只雌性大鼠进行肌内注射 30 μg mRNA/剂的完整人 BNT162b2 剂量（按 mg/kg 计算，> 人剂量的 300 倍）。一半的大鼠在妊娠结束时接受剖腹产和全面的胎儿检查，另一半允许分娩并监测至哺乳结束。在交配前以及妊娠和哺乳结束时证实了强烈的中和抗体反应。胎儿和后代中也证实存在中和抗体。正如其他动物研究所预期的那样，并且与人类的观察结果一致，在水坝中注意到了与局部注射部位反应相关的非不良影响。 BNT162b2 对雌性交配性能、生育力或任何卵巢或子宫参数没有影响，也对哺乳期结束时后代的胚胎-胎儿或出生后存活、生长、身体发育或神经功能发育没有影响。结合非妊娠人群的安全性概况，这一符合 ICH 要求的非临床安全性数据支持 BNT162b2 在育龄妇女以及孕妇和哺乳期妇女中的研究。
BNT162b2 is a vaccine developed to prevent coronavirus disease 2019 (COVID-19). BNT162b2 is a lipid nanoparticle formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein locked in its prefusion conformation. A developmental and reproductive toxicity study was conducted in rats according to international regulatory guidelines. The full human BNT162b2 dose of 30 μg mRNA/dose (>300 times the human dose on a mg/kg basis) was administered intramuscularly to 44 female rats 21 and 14 days prior to mating and on gestation days 9 and 20. Half of the rats were subject to cesarean section and full fetal examination at the end of gestation, and the other half were allowed to deliver and were monitored to the end of lactation. A robust neutralizing antibody response was confirmed prior to mating and at the end of gestation and lactation. The presence of neutralizing antibodies was also confirmed in fetuses and offspring. Nonadverse effects, related to the local injection site reaction, were noted in dams as expected from other animal studies and consistent with observations in humans. There were no effects of BNT162b2 on female mating performance, fertility, or any ovarian or uterine parameters nor on embryo-fetal or postnatal survival, growth, physical development or neurofunctional development in the offspring through the end of lactation. Together with the safety profile in nonpregnant people, this ICH-compliant nonclinical safety data supports study of BNT162b2 in women of childbearing potential and pregnant and lactating women.
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影响因子：
2.9
作者：
Banerjee J;Mullins E;Townson J;Playle R;Shaw C;Kirby N;Munnery K;Bourne T;Teoh TG;Dhanjal M;Poon L;Wright A;Lees C
通讯作者：
Lees C
影响因子：
13.8
作者：
Edlow AG;Li JZ;Collier AY;Atyeo C;James KE;Boatin AA;Gray KJ;Bordt EA;Shook LL;Yonker LM;Fasano A;Diouf K;Croul N;Devane S;Yockey LJ;Lima R;Shui J;Matute JD;Lerou PH;Akinwunmi BO;Schmidt A;Feldman J;Hauser BM;Caradonna TM;De la Flor D;D'Avino P;Regan J;Corry H;Coxen K;Fajnzylber J;Pepin D;Seaman MS;Barouch DH;Walker BD;Yu XG;Kaimal AJ;Roberts DJ;Alter G
通讯作者：
Alter G
影响因子：
120.7
作者：
Bianchi, Diana W.;Kaeser, Lisa;Cernich, Alison N.
通讯作者：
Cernich, Alison N.
影响因子：
9.8
作者：
Minkoff H;Ecker J
通讯作者：
Ecker J
影响因子：
1.3
作者：
Makris, Susan L.;Solomon, Howard M.;Wise, L. David
通讯作者：
Wise, L. David