COVID-19 mRNA vaccine (Tonix)

Lipid nanoparticles (LNPs) are a type of lipid vesicles that possess a homogeneous lipid core. These vesicles are widely used in small-molecule drug and nucleic acid delivery and recently gained much attention because of their remarkable success as a delivery platform for COVID-19 mRNA vaccines. Nonetheless, the utility of transient protein expression induced by mRNA extends far beyond vaccines against infectious diseases─they also hold promise as cancer vaccines, protein replacement therapies, and gene editing components for rare genetic diseases. However, naked mRNA is inherently unstable and prone to rapid degradation by nucleases and self-hydrolysis. Encapsulation of mRNA within LNPs protects mRNA from extracellular ribonucleases and assists with intracellular mRNA delivery.In this Account, we discuss the core features of LNPs for RNA delivery. We focus our attention on LNPs designed to deliver mRNA; however, we also include examples of siRNA-LNP delivery where appropriate to highlight the commonalities and the dissimilarities due to the nucleic acid structure. First, we introduce the concept of LNPs, the advantages and disadvantages of utilizing nucleic acids as therapeutic agents, and the general reasoning behind the molecular makeup of LNPs. We also briefly highlight the most recent clinical successes of LNP-based nucleic acid therapies. Second, we describe the theory and methods of LNP self-assembly. The common idea behind all of the preparation methods is inducing electrostatic interactions between the nucleic acid and charged lipids and promoting nanoparticle growth via hydrophobic interactions. Third, we break down the LNP composition with special attention to the fundamental properties and purposes of each component. This includes the identified molecular design criteria, commercial sourcing, impact on intracellular trafficking, and contribution to the properties of LNPs. One of the key components of LNPs is ionizable lipids, which initiate electrostatic binding with endosomal membranes and facilitate cytosolic release; however, the roles of other lipid components should not be disregarded, as they are associated with stability, clearance, and distribution of LNPs. Fourth, we review the attributes of LNP constructs as a whole that can heavily influence RNA delivery. These attributes are LNP size, charge, internal structure, lipid packing, lipid membrane hydration, stability, and affinity toward biomacromolecules. We also discuss the specific techniques used to examine these attributes and how they can be adjusted. Finally, we offer our perspective on the future of RNA therapies and some questions that remain in the realm of LNP formulation and optimization.

The present study is about the immediate-type hypersensitivity to polyethylene glycol (PEG) and a PEG-containing COVID-19 vaccine revealed by intradermal testing.We report the case of a patient who experienced anaphylaxis after administration of PEG-containing drugs and after intradermal testing (IDT) with the PEG-containing BNT162b2 vaccine.A 24-yr-old woman came to our department with anaphylactic episodes after exposure to various drugs.Shortly after oral intake of metamizole and sultamicillin tablets, she developed numbness in her hands, generalized pruritus, flushing, angioedema, dyspnea, and weakness before finally losing consciousness.A similar event occurred after extensive topical application of diclofenac ointment.She also had allergic rhinoconjunctivitis.Her daily medication consisted of oral hormonal contraception and occasional intake of ibuprofen tablets, which were well tolerated.Laboratory anal. revealed serum IgE of 109 kU/L (with no IgE-mediated sensitization to beta-lactams [ie, penicilloyl G and V, ampicilloyl, amoxicilloyl], a-galactosidase, or ethylene oxide) and serum mast cell tryptase of 2.3 ug/L (all Thermo Fisher Scientific).For more detailed information on serum IgE anal. and allergen provocation tests, see the Online Repository at www.jiaci.organic Skin prick tests (SPTs) with individual pharmaceutical products yielded pos. results to ibuprofen, metamizole, and penicillin V, but not to other nonsteroidal anti-inflammatory drugs or beta-lactams.Notably, some results were not in accordance with the patients' history of potential hypersensitivity to the active ingredients of the drugs.At that time, the patient experienced another anaphylactic reaction characterized by lip angioedema, dizziness, and dyspnea within minutes after inadvertent ingestion of a spoonful of yogurt mixed with a laxative for toddlers containing macrogol(PEG) with a mol. weight (MW) of 4000.The results of SPT with this compound were pos., and a comprehensive inspection of all previously tested medications revealed that she had had a pos. SPT result only to drugs containing PEG with a higher MW (Table E1), thus indicating clin. relevant immediate-type sensitization to PEG.Accordingly, subsequent oral challenges with tablets containing the corresponding active substances but not PEG were all tolerated.PEG serves as a solvent and as a stabilizer in various pharmaceutical products, including the recently approved COVID-19 mRNA vaccines.Thus, the diagnostic work-up was extended to one vaccine containing PEG2000 (BNT162b2) and another comprising polysorbate 80 as a PEG-cross-reactive ingredient (AZD1222, COVID-19 vaccine, AstraZeneca), as well as various vaccine excipients (Table).While SPT was pos. only to PEG6000, IDTs with the resp. substances performed on consecutive days were pos. for both vaccines.Shortly after administration of BNT162b2, the patient experienced itching on the palate and inner thighs, dizziness, and shortness of breath requiring i.v. treatment with antihistamines and corticosteroids.