2. Academic Validation
  3. Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model

Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model

  • Arch Toxicol. 2025 Feb;99(2):755-773. doi: 10.1007/s00204-024-03912-1.
Jae-Hun Ahn # 1,  Jisun Lee # 2,  Gahyun Roh # 2 3,  Na-Young Lee 1 4,  Hee-Jin Bae 1,  Euna Kwon 1,  Kang-Min Han 5 6,  Ji-Eun Kim 1,  Hyo-Jung Park 2 3,  Soyeon Yoo 7,  Sung Pil Kwon 7,  Eun-Kyoung Bang 7,  Gyochang Keum 7,  Jae-Hwan Nam 8 9,  Byeong-Cheol Kang 10 11 12
Affiliations

Affiliations

  • 1 Department of Experiment Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
  • 2 Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Republic of Korea.
  • 3 BK Four Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.
  • 4 Department of Veterinary Pathology and Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
  • 5 Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 6 Department of Pathology, CHA Ilsan Medical Center, CHA University, Goyang-si, Republic of Korea.
  • 7 Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.
  • 8 Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Republic of Korea. jhnam@catholic.ac.kr.
  • 9 BK Four Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea. jhnam@catholic.ac.kr.
  • 10 Department of Experiment Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. bckang@snu.ac.kr.
  • 11 Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. bckang@snu.ac.kr.
  • 12 Department of Veterinary Pathology and Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. bckang@snu.ac.kr.
  • # Contributed equally.
PMID: 39656241 DOI: 10.1007/s00204-024-03912-1
Abstract

The increasing use of SARS-CoV-2 mRNA vaccines has raised concerns about their potential toxicological effects, necessitating further investigation to ensure their safety. To address this issue, we aimed to evaluate the toxicological effects of SARS-CoV-2 mRNA vaccine candidates formulated with four different types of lipid nanoparticles in ICR mice, focusing on repeated doses and administration routes. We conducted an extensive analysis in which mice received the mRNA vaccine candidates intramuscularly (50 μg/head) twice at 2-week intervals, followed by necropsy at 2 and 14 dpsi (days post-secondary injection). In addition, we performed a repeated dose toxicity test involving three, four, or five doses and compared the toxicological outcomes between intravenous and intramuscular routes. Our findings revealed that all vaccine candidates significantly induced SARS-CoV-2 spike protein-specific IgG and T cell responses. However, at 2 dpsi, there was a notable temporary decrease in lymphocyte and reticulocyte counts, anemia-related parameters, and significant increases in cardiac damage markers, troponin-I and NT-proBNP. Histopathological analysis revealed severe inflammation and necrosis at the injection site, decreased erythroid cells in bone marrow, cortical atrophy of the thymus, and increased spleen cellularity. While most toxicological changes observed at 2 dpsi had resolved by 14 dpsi, spleen enlargement and injection site damage persisted. Furthermore, repeated doses led to the accumulation of toxicity, and different administration routes resulted in distinct toxicological phenotypes. These findings highlight the potential toxicological risks associated with mRNA vaccines, emphasizing the necessity to carefully consider administration routes and dosage regimens in vaccine safety evaluations, particularly given the presence of bone marrow and immune organ toxicity, which, though eventually reversible, remains a serious concern.

Keywords

Lipid nanoparticle; SARS-CoV-2; Safety; Toxicity; mRNA vaccine.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-145405
    99.91%, 阳离子类脂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z