SARS-CoV2 mRNA Vaccine Intravenous Administration Induces Myocarditis in Chronic Inflammation

Ha-Eun Jeon, Seonghyun Lee, Jisun Lee, Gahyun Roh, Hyo-Jung Park, Yu-Sun Lee, Yeon-Jung Kim, Hong-Ki Kim, Ji-Hwa Shin, You-Jeung Lee, Chae-Ok Gil, Eun-Seok Jeon, Jae-Hwan Nam, Byung-Kwan Lim.

Abstract

The current COVID-19 mRNA vaccines were developed and applied for pandemic-emergent conditions. These vaccines use a small piece of the virus’s genetic material (mRNA) to stimulate an immune response against COVID-19. However, their potential effects on individuals with chronic inflammatory conditions and vaccination routes remain questionable. Therefore, we investigated the effects of mRNA vaccines in a mouse model of chronic inflammation, focusing on their cardiac toxicity and immunogenicity dependent on the injection route.

Introduction

Coronavirus vaccines have been widely used as a critical measure in response to the global coronavirus infection (COVID-19) pandemic. The current COVID-19 mRNA vaccines, including Pfizer-BioNTech and Moderna, were developed and applied for pandemic emerging conditions. These vaccines use a small piece of the virus’s genetic material (mRNA) to stimulate an immune response against COVID-19. This mRNA instructs the cells to produce a harmless piece of the virus called the spike protein.

Materials and Methods:

The antigen was designed using a DNA encoding the spike protein of the SARS-CoV-2 Omicron variant. The mRNA vaccine plasmid was produced by inserting the antigen DNA into multiple cloning sites on the mRNA platform. It was produced using the EZ T7 High Yield In vitro Transcription Kit (Enzynomics, Daejeon, Korea), according to the manufacturer’s protocol. Total mRNA was precipitated using lithium chloride and purified using cellulose, which was previously described.

Discussion

We investigate the impact of mRNA vaccines on low and sustained levels of inflammation, such as atherosclerosis. We established an animal model that induced chronic inflammation by using an LPS mini-pump system for the constitutive release of LPS for 4weeks. We successfully established a chronic inflammation model and mRNA vaccine administrated through IV or IM injection. In a Balb/c mouse with male mice, IV but not IM administration of COVID-19 mRNA vaccine in chronic inflammatory condition induced acute myocarditis and/or pericarditis with increased inflammatory cytokine transcription, cardiomyocyte damage and inflammatory cell infiltration in the heart within 2-day post injection (dpi) of the second vaccination.

Citation: Jeon H-E, Lee S, Lee J, Roh G, Park H-J, Lee Y-S, et al. (2024) SARS-CoV2 mRNA vaccine intravenous administration induces myocarditis in chronic inflammation. PLoS ONE 19(10): e0311726. https://doi.org/10.1371/journal.pone.0311726

Editor: Mohammed Misbah Ul Haq, Deccan School of Pharmacy, INDIA

Received: February 3, 2024; Accepted: September 19, 2024; Published: October 10, 2024.

Copyright: © 2024 Jeon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: 1. The Ministry of Food and Drug Safety (No. 22213MFDS421, J.H. Nam; 22203MFDS403-1, B.K. Lim). 2. The Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (No. HV22C0160, B.K. Lim) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.