Question Number: 337
PDR Number: SQ22-000715
Date Submitted: 21/11/2022
Department or Body: Department of Health

The presence of cationic lipids in blood from the lipid nanoparticles (LNPs) used in the COVID-19 mRNA vaccines was not investigated in nonclinical or clinical studies. In a biodistribution study in rats with LNPs (containing a radiolabelled lipid marker) encapsulating luciferase mRNA, the lipid marker (i.e. radioactivity) was mainly detected in the injection site and liver with low levels in the spleen, adrenal glands and ovaries. Very low levels were detected in blood and these rapidly decreased from 2 ?g lipid equivalent per mL of blood at 25 minutes after injection to 0.42 ?g equivalent/mL at 48 h, compared with 165 ?g equivalent/g in the tissue at the injection site at 48 h. It is unclear whether the radioactivity detected in blood was the unchanged lipid maker or the breakdown products of the marker. It should be noted that the LNP dose in this distribution study in rats was considerably higher than the human dose on a µg/kg body weight basis. Therefore, much lower amounts of lipids, if any, would be found in the circulating blood of vaccinated people. Lipids in blood donated from COVID-19 vaccinees three days after vaccination should be very low or undetectable. Very low levels of cationic lipid present in donated blood should not cause any harm. In repeat dose toxicity studies in rats, doses of LNPs in the Pfizer vaccine approximately 100 times the human clinical dose did not cause systemic toxicity (including effects on fertility or pregnancy) except for local reactions at the injection site and immune response-related findings. Similarly, repeat dose toxicity and reproductive toxicity studies in rats with vaccine formulations containing LNPs used in the Moderna COVID-19 vaccine or other vaccines containing the same LNPs at LNP doses up to 50 times the human clinical dose showed no systemic toxicity.