Developmental and reproductive toxicity (DART) study of a novel SARS-CoV-2 tetravalent recombinant protein vaccine (SCTV01E) in rats

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-03-04 DOI:10.1016/j.reprotox.2025.108878

Xiao Zhang , Jilei Jia , Gaojian Chen , Dan Meng , Juan Ma , Huimin Wang , Shaozheng Zhou , Lin Ma , Qianqian Qian , Xuejie Liu , Xuefeng Li , Liangzhi Xie

{"title":"Developmental and reproductive toxicity (DART) study of a novel SARS-CoV-2 tetravalent recombinant protein vaccine (SCTV01E) in rats","authors":"Xiao Zhang , Jilei Jia , Gaojian Chen , Dan Meng , Juan Ma , Huimin Wang , Shaozheng Zhou , Lin Ma , Qianqian Qian , Xuejie Liu , Xuefeng Li , Liangzhi Xie","doi":"10.1016/j.reprotox.2025.108878","DOIUrl":null,"url":null,"abstract":"<div><div>SCTV01E, a novel SARS-CoV-2 tetravalent protein vaccine containing recombinant spike proteins of Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron BA.1 (B.1.1.529.1) variants and SCTVA02B adjuvant, has received Emergency Use Authorization (EUA) in China and the United Arab Emirates (UAE) as a next-generation COVID-19 vaccine. A comprehensive reproductive and developmental toxicity evaluation was conducted in Sprague-Dawley (SD) rats under Good Laboratory Practice (GLP) conditions. Maternal animals were intramuscularly injected with 1 × or 3 × the highest human dose every other week prior to mating, followed by booster immunizations during gestation and lactation periods. The main findings showed that SCTV01E vaccination elicited robust binding IgG and neutralizing antibody responses against all four target variants. While no vaccine-related adverse reproductive effects were observed in parental male or female rats, transient injection site reactions and slight, reversible reductions in body weight gain and food consumption were noted. Key developmental parameters were not affected, and postnatal evaluation revealed no evidence of embryo-fetal malformations, developmental delays, or functional impairments in offspring. These results suggest a favorable safety profile for SCTV01E and its possible suitability for clinical trials in humans of reproductive potential. Furthermore, the efficient transplacental and lactational transfer of maternal antibodies observed in animal models suggests a potential protection: direct immunization of mothers may confer passive immunity to both fetuses in utero and neonates during breastfeeding.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108878"},"PeriodicalIF":3.3000,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890623825000498","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

SCTV01E, a novel SARS-CoV-2 tetravalent protein vaccine containing recombinant spike proteins of Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron BA.1 (B.1.1.529.1) variants and SCTVA02B adjuvant, has received Emergency Use Authorization (EUA) in China and the United Arab Emirates (UAE) as a next-generation COVID-19 vaccine. A comprehensive reproductive and developmental toxicity evaluation was conducted in Sprague-Dawley (SD) rats under Good Laboratory Practice (GLP) conditions. Maternal animals were intramuscularly injected with 1 × or 3 × the highest human dose every other week prior to mating, followed by booster immunizations during gestation and lactation periods. The main findings showed that SCTV01E vaccination elicited robust binding IgG and neutralizing antibody responses against all four target variants. While no vaccine-related adverse reproductive effects were observed in parental male or female rats, transient injection site reactions and slight, reversible reductions in body weight gain and food consumption were noted. Key developmental parameters were not affected, and postnatal evaluation revealed no evidence of embryo-fetal malformations, developmental delays, or functional impairments in offspring. These results suggest a favorable safety profile for SCTV01E and its possible suitability for clinical trials in humans of reproductive potential. Furthermore, the efficient transplacental and lactational transfer of maternal antibodies observed in animal models suggests a potential protection: direct immunization of mothers may confer passive immunity to both fetuses in utero and neonates during breastfeeding.

查看原文本刊更多论文

新型SARS-CoV-2四价重组蛋白疫苗（SCTV01E）对大鼠的发育和生殖毒性（DART）研究

SCTV01E是一种新型SARS-CoV-2四价蛋白疫苗，含有α (B.1.1.7)、β (B.1.351)、Delta （B.1.617.2）和Omicron BA.1 （B.1.1.529.1）变异体和SCTVA02B佐剂的重组刺突蛋白，已在中国和阿拉伯联合酋长国（阿联酋）获得紧急使用授权（EUA），作为下一代COVID-19疫苗。在良好实验室规范（GLP）条件下，对SD大鼠进行了全面的生殖和发育毒性评价。母动物在交配前每隔一周肌肉注射人体最高剂量的1或3倍，然后在妊娠期和哺乳期加强免疫。主要研究结果表明，SCTV01E疫苗接种可引发针对所有四种靶变异体的强效结合IgG和中和抗体反应。虽然在亲本雄性或雌性大鼠中没有观察到与疫苗相关的不良生殖影响，但注意到短暂的注射部位反应和体重增加和食物消耗的轻微可逆减少。关键的发育参数没有受到影响，产后评估显示没有证据表明胚胎-胎儿畸形，发育迟缓，或后代的功能障碍。这些结果表明SCTV01E具有良好的安全性，可能适用于具有生殖潜能的人的临床试验。此外，在动物模型中观察到的母体抗体经胎盘和哺乳期的有效转移表明了一种潜在的保护作用：母亲的直接免疫可能使子宫内胎儿和母乳喂养期间的新生儿获得被动免疫。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.