Lipid Nanoparticles and Their Link to TTS, GBS, and Spike-Associated Mechanisms

Recent studies have raised concerns about the potential role of lipid nanoparticles (LNPs) in triggering immune-related conditions. Evidence suggests a possible connection between LNPs and thrombosis with thrombocytopenia syndrome (TTS), as well as Guillain-Barré syndrome (GBS).

Researchers have also explored how prions, exosomes, and spike proteins may contribute to these outcomes by influencing cellular communication and immune responses.

While the mechanisms are still being investigated, the growing body of research highlights the need for deeper evaluation of how LNP-based therapies may interact with the body’s clotting and neurological systems.

When considering the rare side effects linked to different COVID-19 vaccines, there is a notable variation in the incidence of conditions such as thrombosis with thrombocytopenia syndrome (TTS) and Guillain-Barré syndrome (GBS) across the various vaccine platforms.

Thrombosis with Thrombocytopenia Syndrome (TTS)

• The adenovirus vector vaccines, specifically the AstraZeneca (ChAdOx1 nCoV-19) and Janssen (Johnson & Johnson) vaccines, have been associated with TTS. This rare side effect is characterized by blood clots accompanied by low levels of platelets in the blood. It has been reported more frequently in women under 50 years of age for the Janssen vaccine (CDC).

Guillain-Barré Syndrome (GBS)

• GBS has also been linked to the Janssen vaccine. This condition involves the body's immune system damaging nerve cells, resulting in muscle weakness and, in some cases, paralysis. The occurrence of GBS has been reported as an infrequent event following vaccination (CDC).

Cardiac-related Side Effects

• Myocarditis and pericarditis are rare cardiac side effects mainly reported after mRNA COVID-19 vaccinations, particularly with the Pfizer-BioNTech and Moderna vaccines. These side effects are more commonly observed in male adolescents and young adults (MDPI).

The mechanisms behind these side effects are not fully elucidated but may involve immune system reactions. For instance:

• Lipid nanoparticles (LNPs) in mRNA vaccines facilitate the delivery of mRNA into cells but are not known to cause these side effects directly. Instead, they encapsulate mRNA to protect it until it can be taken up by cells.
• The spike protein, which is generated in the body following vaccination with any of the COVID-19 vaccines, is thought to be a potential trigger for immune reactions due to its foreign nature, which may explain some of the inflammatory responses, such as myocarditis.
• There is no evidence from the clinical trials and ongoing surveillance to suggest that prions or exosomes are involved in vaccine-induced side effects.

It is crucial to continue monitoring the safety profiles of these vaccines and investigate any new data that emerges to understand better the pathomechanisms involved in these rare but serious adverse events.