mRNA COVID-19 Vaccine(LiveRNA Therapeutics Inc.)

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.

In late 2019, the World Health Organization declared Coronavirus disease 2019 a global emergency. Since then, many vaccines have been developed to combat the pandemic. Millions of people have received one of the approved COVID-19 vaccines; unfortunately, some adverse events also have been recorded.

In the local health system, patients could get either mRNA vaccines (either Pfizer-BioNTech or Moderna), adenoviral vector vaccine (AstraZeneca), or the vaccine based on inactivated virus (Sinovac). We investigated what immune-mediated adverse events occurred in our department after the COVID-19 vaccination.

We evaluated six patients from our center who received mRNA vaccines and developed suspected immune-mediated adverse events. The immune-mediated adverse events are characterized by de novo or relapsing glomerular diseases and are further confirmed with percutaneous kidney biopsies. During A follow-up of more than two years, remission occurred in five patients, and glomerulonephritis persisted in one of them.

Vaccinations are pivotal in effectively protecting and preventing various epidemics. As such, it is essential to maintain a high level of vigilance concerning post-vaccination adverse events. This heightened level of suspicion leads to earlier detection, better understanding, and optimal prevention and management of these events. To this end, developing a specific vaccine/patient risk profile is necessary to categorize the target population selectively.