Lipid nanoparticles in COVID-19 vaccines: The new mercury to antivaxxers
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I was recently interviewed by a local reporter regarding COVID-19 vaccination. Although I don’t know if anything I said will end up in the final story as published, one thing I thought worth recounting is something that I told her when she asked me if there was anything else I wanted to emphasize that hadn’t been covered. My response? I told her that, when it comes to the antivaccine movement, there is nothing new under the sun and that none of its propaganda and disinformation about COVID-19 vaccines is new. It’s the same old antivaccine misinformation, tropes, misrepresentations of science, and propaganda, just repackaged for COVID-19 vaccines. I’ve already written about a number of examples. The most frequently used example thus far has been to weaponize anecdotes of death after the vaccine that likely had nothing to do with the vaccine, much as, pre-pandemic, antivaxxers had weaponized anecdotes of sudden infant death syndrome (SIDS) after vaccination, all to demonize vaccines. Other examples include claiming that vaccines cause female infertility; that they “damage” or “alter” your DNA, or that COVID-19 is not dangerous (or isn’t even real at all) in much the same way antivaxxers used to claim that measles and other vaccine-preventable diseases aren’t dangerous (the implication being that vaccines are unnecessary). Then, of course, there is the ever-popular strategy of fear mongering about reports made to the Vaccine Adverse Event Reporting System (VAERS) database, implying that they indicate causation. All techniques antivaxxers used extensively pre-pandemic. So it should be no surprise that antivaxxers are also using a variant of a longtime favorite trope, the “toxins gambit“, the claim that vaccines are loaded with horrible “toxins“, a variant being the claim that vaccines have “fetal cells” or “fetal DNA” in them and are thus horrifically contaminated. Heck, that last one has even been used by antivaxxers about COVID-19 vaccines!

Which brings me to lipid nanoparticles, which appear to be the new mercury in vaccines to antivaxxers.

Unsurprisingly, after having tried to misrepresent the mRNA-based vaccines developed and marketed by Moderna and Pfizer/BioNTech as “gene therapy” or something that will corrupt your DNA, it’s no surprise that antivaxxers are now resurrecting a version of the “toxins gambit” to use against these same vaccines and that the target of the gambit are the lipid nanoparticles in the vaccines. Unsurprisingly, über-quack Joe Mercola last week decided to do what he does so frequently and summarize the latest COVID-19 conspiracy theories, this time the “toxins gambit” applied to the lipid nanoparticles, in the form of an article entitled “How Safe Are the Nanoparticles in Moderna’s Vaccine?” And Joe Mercola isn’t the only quack trying to demonize lipid nanoparticles.

A refresher on mRNA vaccines

I briefly discussed lipid nanoparticles when I discussed the antivaccine lie that mRNA-based COVID-19 vaccines will “alter” or “reprogram” your DNA. Even though we’ve discussed it several times, it’s worth discussing again how mRNA vaccines, such as those made by Moderna or Pfizer/BioNTech work, so that you don’t have to click on a lot of links. I’ll start with the basic idea.

The proteins and enzymes that make up cells and organisms are genetically encoded in DNA. DNA is made up of smaller building blocks called nucleotides attached to each other in a linear fashion and packaged in a double helix of two complementary strands wrapped around each other. Proteins are also made up of smaller building blocks, in this case amino acids. The genetic code translates nucleotide sequences into amino acid sequences, with a three nucleotide “word” (codon) specifying a specific amino acid. For purposes of this discussion, the details don’t matter, other than to understand that there is an intermediary between DNA and protein, and that intermediary is RNA. Messenger RNA (mRNA) is synthesized based on the DNA template in the nucleus, transported out of the nucleus, and then set upon by large protein complexes known as ribosomes, which build proteins based on the sequence encoded by the mRNA. The process is a bit more complex than that (for example, the initial RNA synthesized is often spliced into a shorter RNA before being translated into protein, and proteins often have modifications made after their synthesis), but these are the basics.

mRNA vaccines take advantage of this process. Traditional vaccines use killed pathogenic organisms or whole or fragments of proteins from the organism as antigens to provoke an immune response. The problem with this method is that it’s a lot more involved and time-consuming to manufacture the proteins or to grow up the organism then inactivate it to use in vaccines. There are many theoretical advantages to using mRNA instead. For one thing, it’s a lot easier to make large quantities of RNA than it is to make large quantities of protein. For another thing, if a new version of a vaccine is needed, it’s not difficult to just change the sequence of the RNA without altering the rest of the formulation, something that will likely become very important as the need arises to make new vaccines to combat the various variants of SARS-CoV-2 that are cropping up and might eventually evade the vaccine-based immunity. In brief, there’s a lot of advantage to using the recipient’s cells’ own machinery to manufacture the protein used as an antigen to provoke an immune response. In the case of the COVID-19 vaccine, both the Moderna and Pfizer/BioNTech versions of the vaccine use the mRNA encoding the SARS-CoV-2 spike protein, the protein that the virus uses to get into cells.

There are, of course, problems to be overcome with mRNA vaccines. One is that RNA is unstable in aqueous solution, which is why the RNAs used are modified to make them more stable and also why the vaccines need to be stored at such ultralow temperatures, a characteristic that complicated the rollout because many sites didn’t have -80°C freezers to store the vaccines and such freezers cost thousands of dollars. (The -80°C freezer in my lab cost close to $10,000.) The other problem is getting the mRNA into the cells. That’s where the lipid nanoparticles come in.

Lipid nanoparticles

Lipid nanoparticles are small spherical particles made of lipids into which various “payloads” (in the case of the COVID-19 vaccines, mRNA encoding the SARS-CoV-2 spike protein) can be introduced. These particles are generally less than 100 nm in diameter and made up of—you guessed it—lipids. But what are lipids? Basically, mammalian cell membranes are made of phospholipids. Each lipid molecule in the membrane has two ends, a “head” and two tails. The “head” contains an ionic phosphate group that has affinity towards water and ions, while the two tails are long stretches of hydrocarbon molecule (just carbon and hydrogen) and is hydrophobic (insoluble in water). These molecules are referred to as amphiphilic (from the Greek αμφις, amphis: both and φιλíα, philia: love, friendship), having affinity for both water and hydrocarbons. Many molecules are amphiphilic, including detergents and soaps.

Lipid bilayer

Lipid bilayer

Molecules like this can form two kinds of structures, micelles or liposomes. In cells, these amphiphilic phospholipids form a two-layered structure, with the hydrophilic heads facing the aqueous solution and the two-tailed hydrophobic structures facing each other. These bilayers can form spheres, as illustrated below:

Phospholipids

Phospholipids

Micelles and bilayers

Lipid micelles and bilayers.

As a pseudonymous pharmaceutical scientist wrote:

If you have been preparing salad dressing with vegetable oil and vinegar, you likely notice that the oil droplets would aggregate together into one big slick, whereas you will notice a clear interface between the vinegar and the oil slick. This is because the lipids present in the vegetable oil will align their hydrophobic tails inside the droplet and expose their hydrophilic head outside to interact with the water molecules of the vinegar. This is what we call “micelles”. If you work hard enough, you can create structures called “liposomes” that are able to cage water and solutes within the oil slick, separating from the rest of the water of the vinegar by having a lipid layer.

Liposomes, when used for drug delivery, look like this representation:

Liposome with payload

Liposome with payload.

So why use liposomes? In general, the reason to use liposomes to deliver drugs is to get a hydrophilic (water-loving, water-soluble) molecule through the lipid bilayer that makes up a cell and into the cell’s cytoplasm. mRNA, it turns out, is hydrophilic and easily dissolved in aqueous solution; so naturally when scientists started trying to use mRNA in vaccines a couple of decades ago liposomes were a natural choice as the delivery vehicle to get the mRNA to the cells. And, as I’ve alluded to before, antivaxxers are keen to blame all sorts of bad things on lipid nanoparticles. It’s basically a variant of the “toxins gambit” in which lipid nanoparticles are portrayed as being something potentially toxic and deadly.

Mercola and false comparisons

Now that I’ve briefly recounted what lipid nanoparticles are and why they’re used in the Moderna and Pfizer/BioNTech COVID-19 vaccines, let’s take a look at the antivaccine disinformaton about them being spread by Joe Mercola:

Moderna and Pfizer are using lipid nanoparticles that contain polyethylene glycol (PEG)2 for this purpose. The mRNA is wrapped in lipid nanoparticles (LNPs) that carry it to your cells, and the LNPs are “PEGylated” — that is, chemically attached to PEG molecules to increase stability.

This experimental mRNA gene therapy and its lipid nanoparticle-based delivery system have never been approved for use in a vaccine or drug. This includes Pfizer’s and Moderna’s COVID-19 vaccines, which were only “authorized” for emergency use by the U.S. Food and Drug Administration — not “approved.”

Significant concerns have been raised over the technology, including the lipid nanoparticles, and Moderna actually abandoned it in 2017 after studies revealed a high rate of adverse effects.

That certainly sounds…ominous. Or does it? One of the references cited by Mercola is, unsurprisingly, an article published on Robert F. Kennedy Jr.’s antivaccine website Children’s Health Defense, in which RFK Jr. quoted a statement by Moderna:

[T]here can be no assurance that our LNPs will not have undesired effects. Our LNPs could contribute, in whole or in part, to one or more of the following: immune reactions, infusion reactions, complement reactions, opsonation reactions, antibody reactions . . . or reactions to the PEG from some lipids or PEG otherwise associated with the LNP. Certain aspects of our investigational medicines may induce immune reactions from either the mRNA or the lipid as well as adverse reactions within liver pathways or degradation of the mRNA or the LNP, any of which could lead to significant adverse events in one or more of our clinical trials.

This SEC report was dated November 2018. I also note that this is the sort of cautious statement that any scientist would make before a treatment is actually tested in patients. The difference now is that lipid nanoparticles have now been received by tens of millions of patients without significant adverse events.

I also can’t help but note how Mercola is parroting what is seemingly the accepted antivaccine talking point, specifically referring to the Moderna and Pfizer/BioNTech mRNA-based vaccines as “experimental gene therapy”. No, it’s not gene therapy, and, after 70K+ subjects in the clinical trials leading to the FDA’s emergency use authorization (EUA), it’s no longer anything resembling “experimental.” These are just scare words used by the antivaccine movement to invoke doubt and fear regarding these vaccines.

Next up, let’s compare apples to oranges, Joe:

In 2016, Bancel had talked up another of the company’s up-and-coming products, a drug treatment for a rare disease called Crigler-Najjar syndrome. Those with Crigler-Najjar syndrome are missing a liver enzyme needed to break down bilirubin. Moderna’s experimental treatment used mRNA to encode for the missing enzyme, and was encased in LNPs as the delivery agent.

But, as STAT reported in 2017, the treatment was “indefinitely delayed” because it “never proved safe enough to test in humans.” According to STAT:

“… mRNA is a tricky technology. Several major pharmaceutical companies have tried and abandoned the idea, struggling to get mRNA into cells without triggering nasty side effects … The indefinite delay on the Crigler-Najjar project signals persistent and troubling safety concerns for any mRNA treatment that needs to be delivered in multiple doses …

… And for its chemists, those nanoparticles created a daunting challenge: Dose too little, and you don’t get enough enzyme to affect the disease; dose too much, and the drug is too toxic for patients … Moderna could not make its therapy work, former employees and collaborators said. The safe dose was too weak, and repeat injections of a dose strong enough to be effective had troubling effects on the liver in animal studies.”

Let’s look at what the STAT article cited also said. Remember that this article was published three years before the COVID-19 pandemic:

But the Crigler-Najjar treatment has been indefinitely delayed, an Alexion spokeswoman told STAT. It never proved safe enough to test in humans, according to several former Moderna employees and collaborators who worked closely on the project. Unable to press forward with that technology, Moderna has had to focus instead on developing a handful of vaccines, turning to a less lucrative field that might not justify the company’s nearly $5 billion valuation.

“It’s all vaccines right now, and vaccines are a loss-leader,” said one former Moderna manager. “Moderna right now is a multibillion-dollar vaccines company, and I don’t see how that holds up.”

Funny how Mercola didn’t mention this article’s implication that vaccines were not particularly profitable. After all, one of the primary false messages of antivaccine conspiracy theories is that it’s all about the money because vaccines are so insanely profitable.

Of course, comparing vaccines to gene therapy treatments for Crigler-Najjar syndrome is also deceptive. The reason is simple. Replacing an enzyme involved in a critical biochemical process is not the same thing as a vaccine. The targeting isn’t the same in terms of which cells need to produce the protein encoded by the mRNA, and vaccines don’t need nearly the same level of precision when it comes to the amount of protein produced. To be an effective vaccine, all that’s necessary is that there should be a sufficient amount of the protein being used as an antigen to provoke an immune response to “get the attention” of the immune system. The margin for error in reporting an enzyme that is lacking is far less forgiving than the margin for error in producing a protein as an antigen for a vaccine.

But the brain!

Then, of course, there’s the old antivaccine trick of claiming that vaccines cause “neuroinflammation.” First, however:

The mRNA vaccine triggers your body to produce antibodies against the SARS-CoV-2 spike protein, and spike proteins in turn contain syncytin-homologous proteins that are essential for various functions in your body, including the formation of the placenta in pregnant women.

“Syncytin is the name given to the endogenous gamma retrovirus envelope,” Mikovits said, “and we know if it’s expressed overtly in the body in different places … for instance, in the brain, where these lipid nanoparticles will go, then you’ve got multiple sclerosis.”

Remember how I said that I wouldn’t just repeat a debunking of an antivaccine trope? I lied, sort of. The whole “syncytin” thing is merely a repackaging of the antivaccine claim that vaccines will make our women sterile. It’s nonsense.

Then there’s this:

The study’s authors suggested lipid nanoparticles like those in COVID-19 vaccines may be ideal for drug delivery systems because of their ability to bypass the blood brain barrier and “reach the target site due to their small size and ability to dodge the reticular endothelial system.”

I recently interviewed Judy Mikovits, Ph.D., a cellular and molecular biologist, and she agreed that LNPs can enter the brain and contribute to pathologic neuroinflammation, possibly leading to adverse effects like multiple sclerosis or ALS. Additionally, these LNPs carrying the mRNA last for long periods of time, forcing your cells to continuously produce the SARS-CoV-2 spike protein. I encourage you to review my article and interview with Judy.

First off, no. Just no. As I discussed the last time I covered this topic, the mRNA molecules used by these vaccines don’t last long. They just don’t. Moreover, this is yet another example of antivaxxers trying to claim that vaccines cause “neuroinflammation,” no matter how tortured the rationale they have to use to do it.

Then there’s the dreaded PEG:

At least eight people have also had severe allergy-like reactions to Pfizer’s COVID-19 vaccine, prompting NIAID to convene several meetings to discuss the adverse events with officials from Pfizer and Moderna, along with the FDA and independent scientists.

Many suspect the PEG found in both Pfizer’s and Moderna’s vaccines might be the culprit causing allergic reactions and anaphylaxis. PEG has never been used in an approved vaccine, but is used in certain drugs known to cause anaphylaxis. According to Robert F. Kennedy Jr., “studies show that 1 in 7 Americans may unknowingly be at risk of experiencing an allergic reaction to PEG.”

He believes “everyone should be screened for anti-PEG antibodies before getting the Pfizer and Moderna vaccines,” adding that “It is unconscionable that, instead, the FDA and CDC are encouraging people to go ahead and risk a life-threatening anaphylactic reaction and just assume that someone will be on hand to save them.”

Too bad for antivaxxers that a recent study found that anaphylactic reactions to COVID-19 vaccines are rare, 4.7 cases/million doses for the Pfizer vaccine and 2.5 cases/million doses for the Moderna vaccine, well within the range seen for other vaccines and very uncommon, with no deaths reported.

“Toxins” here, “toxins” there, “toxins” everywhere, especially in vaccines

Certain antivaccine canards never die, no matter how many stakes you stick through their heart or how many silver bullets you shoot them with or how many headshots you’ve pumped into them (depending on whether your favorite metaphor is a vampire, werewolf, or zombie, of course). One such canard is what I like to call the “toxins gambit”. Over the years, we’ve seen it used by such antivaccine “luminaries” as Jenny McCarthy and many other antivaxxers. Basically, it consists of listing all sorts of scary-sounding ingredients that are found in vaccines and then trying to argue that vaccines are horrific cesspits of toxins because they contain trace amounts of formaldehyde, for example. It’s a truly stupid, brain dead gambit, but no matter how many times it’s slapped down, there will always be some ignorant antivaccinationist who will resurrect it. (It’s like a lot of antivaccine misinformation that way, actually, but even more so.)

Because the “toxins gambit” is such hoary old bit of antivaccine misinformation, it should surprise no one that it’s been resurrected, much like slashers like Jason, who, after seemingly having been killed at the end of the last movie, always find a way to come back to kill again in the next. Demonizing lipid nanoparticles in the most recent crop of vaccines is just its latest iteration.

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