In this series, "Promise or Peril: Alarming COVID-19 mRNA Vaccine Issues," we explore how the introduction of mRNA technology lacked an adequate regulatory framework, setting the stage for serious adverse events and other concerns related to inadequate safety testing of lipid nanoparticles, spike protein, and residual DNA and lipid-related impurities, as well as truncated/modified mRNA species.
Summary of Key Facts:
- The lipid nanoparticle (LNP) capsule contains the active ingredient messenger RNA (mRNA).
- The LNP is formed by lipids "teaming up" together to form a ball.
- LNP molecules offer great potential as a delivery vehicle, however, the design of the LNP can cause harm.
- The LNP capsule can cluster with other LNPs or fall apart after injection, potentially causing clotting.
- If the LNP capsule falls apart, loose strands of mRNA can circulate in the blood.
- Because the mRNA is negatively charged, loose mRNA in the blood can cause clotting if it clusters with positively charged molecules.
- The LNP capsule lipids also have properties that may cause clotting or trigger the immune system to overreact.
- Researchers knew about these possibilities before the vaccines were authorized.
- The regulatory agencies knew about the possibility of harmful effects before they were even injected into the body.
- The possibility of multiple boosters causing harm was also known before authorization.
- As time passes, we are learning more about the possible mechanisms behind these adverse events.
LNP Design FeaturesThe LNP is a capsule comprised of four different lipids carrying the mRNA inside.
Imagine a drop of oil descending into a glass of water. The oil does not disperse in the water—it stays together. This is how the LNPs stay together to carry the mRNA to a cell membrane where it can be absorbed.
Certain features of the lipids cause them to organize into the LNP capsule shape. The tail of the lipid is hydrophobic, meaning it does not mix with water because it has a neutral charge. The head of the lipid is a phosphate that has an electrical charge, making it hydrophilic. These features cause them to organize themselves.
The lipids gather together—tails pointing in and heads pointing out—creating a ball, as pictured below. When the polyethylene glycol (PEG) adheres to a lipid, the PEG-lipid helps to stabilize the molecule, encouraging it to form smaller LNPs and preventing it from adhering to proteins in the blood.
LNP Design Dilemmas: Stability Versus FragilityThe LNP design dilemma had serious implications: whether to create a stable LNP capsule that does not fall apart readily or a more fragile capsule that breaks down quickly. This design challenge affects how the capsule behaves in the body.
For vaccination, however, the opposite effect is desired: the LNP needs to be less stable so it will dissolve quickly at the injection site and release the fragile mRNA immediately. Otherwise, it will allow the LNP to travel throughout the human body to an unintended organ or tissue.
LNP Design Features Affect ClottingIn addition to the challenge of creating a stable LNP that breaks down quickly at the injection site, the LNP design may also cause clustering leading to clotting. If the LNP falls apart, the charges on the lipids and the loose mRNA may promote interactions with other substances in the blood.
LNPs Can Cluster and Cause ClottingWhen the LNPs diffuse into the blood system, the tiny particles can increase in size based on the Ostwald ripening phenomenon. This is a process in which small crystals dissolve in solution and then redeposit, forming larger clusters.
When thromboses occur within blood vessels, blood flow to critical organs can be obstructed. This includes the heart, lungs, kidneys, intestines, and even the brain.
The LNP Can Fall ApartIf the LNP falls apart, two components, the capsule and the mRNA cargo, may cause interactions that promote clotting due to the electrical charge on each component.
Could the challenges of maintaining a strict "cold chain" (freezing temperature required for vaccine stabilization from manufacturing to injection) have introduced the potential for LNPs to fall apart prior to injection?
LNP Engineering Can Alter ClottingNanoparticle interactions can be helpful or harmful. For example, nanoparticles can be engineered to help the blood to clot, which is useful for those with clotting disorders. On the other hand, if LNP interactions with other substances in the blood cause clotting, this is harmful.
What was known about the potential of LNPs to affect clotting before the pandemic?
'Immune Overdrive'Finally, the mRNA was engineered to help it sneak past our natural immune defenses. This clever design feature may have a fatal flaw.
However, if the immune system never notices, then we do not get the intended benefit. Adjuvants, such as aluminum, are added to vaccines for this reason—to wake up the immune system. Once stimulated, the immune system ramps up its production of antibodies and memory T cells.
What Was Known Prior to Authorization?Early research on LNPs suggests the following issues were well-documented before the COVID-19 vaccines were authorized:
These effects were known prior to FDA authorization and strongly suggest that more testing should have been done in humans.