SEARCHOTHERpreclinical research, biomedical research

other·preclinical research, biomedical research, obstetrics and gynecology, immunology·PMC10206582

Developmental and reproductive toxicity of a recombinant protein subunit COVID-19 vaccine (ZF2001) in rats

NPJ Vaccines · 14 authors, 5 centres

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TL;DR

This preclinical study evaluated the developmental and reproductive toxicity of the ZF2001 COVID-19 protein subunit vaccine in Sprague-Dawley rats. The central result was that vaccination with ZF2001 did not affect female fertility, embryo-fetal development, or postnatal development, and it induced antibody transfer to offspring.

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Two nonclinical studies following ICH S5 (R3) guidelines assessed the ZF2001 vaccine in female Sprague-Dawley rats. In the embryo-fetal developmental toxicity (EFD) study, 144 rats received vaccine, adjuvant, or saline intramuscularly before mating and on gestation day 6. In the pre- and postnatal developmental toxicity (PPND) study, 28 rats per group received vaccine or saline before mating and on gestation days 6 and 20, and postnatal day 10. The only noted effect was local injection site reactions in the adjuvant group. The vaccine did not impact mating, fertility, embryo-fetal development, or offspring survival, growth, behavior, or reproductive performance. High titers of binding and neutralizing antibodies were detected in dams and transferred to fetuses/offspring. The findings support clinical trials in pregnant and lactating women.

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other

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preclinical research

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ORIGINAL PAPER

PMC10206582

Developmental and reproductive toxicity of a recombinant protein subunit COVID-19 vaccine (ZF2001) in rats

NPJ Vaccines

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ABSTRACT

ZF2001, a protein subunit vaccine against coronavirus disease 2019 (COVID-19), contains recombinant tandem repeat of dimeric receptor-binding domain (RBD) protein of the SARS-CoV-2 spike protein with an aluminium-based adjuvant. During the development of this vaccine, two nonclinical studies were conducted to evaluate female fertility, embryo-fetal development, and postnatal developmental toxicity in Sprague‒Dawley rats according to the ICH S5 (R3) guideline. In Study 1 (embryo-fetal developmental toxicity, EFD), 144 virgin female rats were randomly assigned into four groups and received three doses of vaccine (25 μg or 50 μg RBD protein/dose, containing the aluminium-based adjuvant), the aluminium-based adjuvant or a sodium chloride injection administered intramuscularly on days 21 and 7 prior to mating and on gestation day (GD) 6. In Study 2 (pre- and postnatal developmental toxicity, PPND), ZF2001 at a dose of 25 μg RBD protein/dose or sodium chloride injection was administered intramuscularly to female rats ( n = 28 per group) 7 days prior to mating and on GD 6, GD 20 and postnatal day (PND) 10. There were no obvious adverse effects in dams, except for local injection site reactions related to the aluminium-based adjuvant (yellow nodular deposits in the interstitial muscle fibres). There were also no effects of ZF2001 on the mating performance, fertility or reproductive performance of parental females, embryo-fetal development, postnatal survival, growth, physical development, reflex ontogeny, behavioural and neurofunctional development, or reproductive performance of the offspring. The strong immune responses associated with binding and neutralising antibodies were both confirmed in dams and fetuses or offspring in these two studies. These results would support clinical trials or the use of ZF2001 in maternal immunisation campaigns, including those involving women with childbearing potential, regardless of pregnancy status.

CITATION EXPORT

Yisheng Song, Jinjin Shao, Guangbiao She et al.. Developmental and reproductive toxicity of a recombinant protein subunit COVID-19 vaccine (ZF2001) in rats. NPJ Vaccines. (2023). https://doi.org/10.1038/s41541-023-00673-3

AUTHORS

14 · 5 CENTRES

Yisheng Song, Jinjin Shao, Guangbiao She, Wanqiang Lv, Guoyu Chen, Jing Liu, Lili Zhang, Chengda Zhang, Jiahong Wang, Ruiyu Tian, Lianpan Dai, George F. Gao, Enqi Huang, Lijiang Zhang

1grid.506977.a0000 0004 1757 7957Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, 310053 China
2grid.506977.a0000 0004 1757 7957Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Hangzhou Medical College (Zhejiang Academy of Medical Sciences), Hangzhou, 310053 China
3grid.506977.a0000 0004 1757 7957Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, 310000 China
4Anhui Zhifei Longcom Biopharmaceutical Co., Ltd, Hefei, 230088 China
5grid.9227.e0000000119573309CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China