What Are Lipid Nanoparticles in mRNA Vaccines?

Vaccines against COVID-19 have been developed with unprecedented speed. In particular, mRNA vaccines — a technology already in clinical trials for other infectious diseases, such as influenza — have shown impressive efficacy in world-wide administration.

However, allergic reactions including anaphylaxis have been found in some people after receipt of mRNA vaccines.^[1]

Anaphylaxis

Anaphylaxis is a potentially life-threatening allergic reaction that can cause rashes, a plummeting blood pressure, shortness of breath, and a fast heartbeat. It can occur with any vaccine, but are usually extremely rare—about one per 1 million doses.

Based on a prospective cohort of health care employees, it found that:^[3]

• 98% without any allergic reactions
• 2% reported some allergic symptoms
• Severe reactions consistent with anaphylaxis occurred at a rate of 2.47 per 10 000 vaccinations.
• All individuals with anaphylaxis recovered without shock or endotracheal intubation.
• Incidence rate of confirmed anaphylaxis in this study > reported by CDC based on passive spontaneous reporting methods (0.025-0.11 per 10 000 vaccinations).^[4]

after the administration of mRNA vaccines—more frequently with the Moderna vaccine compared with Pfizer-BioNTech.

The overall risk of anaphylaxis to an mRNA COVID-19 vaccine remains extremely low and largely comparable to other common health care exposures.^[5]Although cases were clinically compatible with anaphylaxis, the mechanism of these reactions is unknown.

What's LNP?

Lipid nanoparticles (LNPs) have been developed as vehicles for small molecule delivery by the nanomedicine and materials communities and are now a key component of COVID-19 mRNA vaccines.^[6] Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.^[7]

The two mRNA vaccines (i.e., Pfizer and Moderna) both contain mRNA wrapped in lipid nanoparticles (LNPs) that help carry it to human cells but also act as an adjuvant, a vaccine ingredient that bolsters the immune response. The LNPs are “PEGylated”—chemically attached to PEG molecules that cover the outside of the particles and increase their stability and life span.

Polyethylene Glycol (PEG) and Anaphylaxis

Polyethylene Glycol (PEG) has never been used before in an approved vaccine, but it is found in many drugs that have occasionally triggered anaphylaxis.

Some allergists and immunologists believe a small number of people previously exposed to PEG may have high levels of antibodies against PEG, putting them at risk of an anaphylactic reaction to the vaccine:^[2]

• PEGs are also used in everyday products
• Such as toothpaste and shampoo as thickeners, solvents, softeners, and moisture carriers, and they’ve been used as a laxative for decades.
• An increasing number of biopharmaceuticals include PEGylated compounds as well
• As much as 72% of people are estimated to have at least some antibodies against PEGs^[8]
• Mechanism behind PEG-conjugated anaphylaxis is relatively unknown
• The antibody type (i.e., IgE) that causes classical allergic reactions is not involved
• Instead, PEG triggers two other classes of antibodies, IgM and IgG, involved in a branch of the body’s innate immunity called the complement system
• In 1999, a new type of drug-induced reaction was found and dubbed complement activation-related pseudoallergy (CARPA) which was described as:^[9]
• A nonspecific immune response to nanoparticle-based medicines, often PEGylated, that are mistakenly recognized by the immune system as viruses
• With an experimental anticoagulant containing PEGylated RNA, the research team found that every participant with an anaphylaxis had high levels of anti-PEG IgG^[10]

To conclude, an ideal drug delivery system should minimize side-effects and reduce both dosage and dosage frequency.

References

1. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020
2. Suspicions grow that nanoparticles in Pfizer’s COVID-19 vaccine trigger rare allergic reactions
3. Acute Allergic Reactions to mRNA COVID-19 Vaccines (03/08/2021)
4. Shimabukuro TT, Cole M, Su JR. Reports of anaphylaxis after receipt of mRNA COVID-19 vaccines in the US—December 14, 2020-January 18, 2021.  JAMA. Published online February 12, 2021.
5. Kim MH, Lee SY, Lee SE, et al. Anaphylaxis to iodinated contrast media: clinical characteristics related with development of anaphylactic shock.
6. Let’s talk about lipid nanoparticles
7. Nanoparticles as drug delivery systems, Pharmacological Reports, Volume 64, Issue 5,2012,Pages 1020-1037,ISSN 1734-1140.
8. Analysis of Pre-existing IgG and IgM Antibodies against Polyethylene Glycol (PEG) in the General Population
9. Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble CR1 and anti-C5a antibody
10. Pre-existing anti-PEG antibodies are associated with severe immediate allergic reactions to pegnivacogin, a PEGylated aptamer
11. Cell-mimicking nanodecoys neutralize SARS-CoV-2 and mitigate lung injury in a non-human primate model of COVID-19
12. Designing spatial and temporal control of vaccine responses (good)
13. Role of drug delivery technologies in the success of COVID-19 vaccines: a perspective
14. A Startling Compilation: 'Neither Safe Nor Effective'
• She hopes her book will help stop mandatory COVID vaccination for all people because one size does not fit all. The bodies of people are different and react in different ways to drugs, vaccines, and even food.