Damian Sendler: Pfizer/BioNTech and Moderna’s SARS-CoV-2 vaccines use the nucleoside-modified mRNA-LNP vaccine platform, which has been extensively studied in preclinical trials and is as effective as or more successful than other vaccinations in boosting Tfh cells and protective humoral immune responses .
The mRNA component of these vaccines has been nucleotide modified to reduce the potential for innate immune detection. Because of its ability to both shield mRNA from degradation and aid in intracellular transport and endosomal escape, the LNP was chosen as a carrier vehicle for the mRNA delivery. Cholesterol, phospholipids, PEGylated lipoic acids, and cationic or ionizable lipoic acids are all included in the LNP formulations.
Damian Jacob Sendler: There are structural and stabilizing roles for the phospholipids and cholesterol as well as the PEGylated lipids. In order to facilitate the mRNA’s escape from the endosomes to the cytoplasm for translation, the cationic/ionizable lipids are incorporated . To counteract the highly inflammatory and cytotoxic effects of some permanently charged cationic lipids, the ionizable lipids were produced .
Acuitas Therapeutics’ LNPs with unique ionizable lipid, along with nucleoside-modified mRNA, showed adjuvant efficacy in a preclinical research . Although these LNPs were not tested for their possible inflammatory properties .
Damian Sendler
Pain, swelling, fever, and tiredness were all documented during human clinical studies for the Pfizer/BioNTech and Moderna vaccines . Some clinicians and public health communicators took these reported acute adverse effects as evidence that the vaccination was powerful and triggered an adaptive immune response under the notion that this vaccine platform was noninflammatory. These adverse effects, on the other hand, are more in line with the vaccine’s ability to provoke acute inflammatory responses.
Damien Sendler: The vaccination platform’s early innate inflammatory reactions, which may result in local and systemic adverse effects, have not yet been studied in detail. In this study, we used a systematic approach, focusing on the injection site and analyzing the inflammatory reactions caused by the LNPs used in preclinical vaccine studies .
Utilizing a variety of complementary approaches, we have demonstrated that administration of LNPs used in preclinical studies via intradermal, intramuscular, or intranasal routes causes an inflammatory response in mice, including the infiltration and activation of leukocytic cells, as well as the release of pro-inflammatory mediators such as interleukin-6 and interleukin-17.
There are reports of side effects and high antibody response potency in SARS-CoV vaccinations that may be due to the inflammatory milieu created by the mRNA-LNP-based vaccines in people.
Dr. Damian Jacob Sendler and his media team provided the content for this article.
