Fig. 3: Adverse effects of LNPs.

A Mechanisms of vaccine adverse responses, including IgE-mediated allergy, IgM-mediated pseudoallergy, and autoimmune reactions. PEGylated LNPs lead the body to generate anti-PEG antibodies, which can have negative side effects. IgE antibodies bind to FcεRI in mast cells or basophilic granulocytes, key cells of the immediate hypersensitivity reaction. Multiple tyrosine kinases are activated as mediators. B Upon administration of the PEGylated liposome, anti-PEG IgM in the body binds to the liposome, and this complex causes complement activation via the classical complement pathway and is quickly removed from the blood circulation due to Kupffer cell phagocytosis, which is called the accelerated blood clearance (ABC) phenomenon. This anaphylatoxin induces inflammatory mediators by stimulating macrophages, mast cells and basophils. This mediator binds to receptors of autonomic effector cells, endothelial cells, and smooth muscle cells and induces CARPA through activation. C mRNA-LNP-based drugs can cause autoimmunity as follows: (1) mRNA plays the role of autoantigen and triggers the autoimmune process through TLR7; (2) Since LNPs themselves act as an adjuvant, the autoimmune process proceeds through the innate immune response to LNPs; and (3) in the case of mRNA-LNP vaccines, the autoimmune response can be further aggravated because the vaccine itself enhances the immune process.