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Health See other Health Articles Title: Concerns of Lipid Nanoparticle Carrying mRNA Vaccine into the Brain: What to Make of It? Concerns of Lipid Nanoparticle Carrying mRNA Vaccine into the Brain: What to Make of It? Detailing the arguments for and against this concern with input from experts. Shin Jie Yong Mar 19, 2021 · 12 min read We are all-in into vaccinating as many people as possible against Covid-19, with mRNA vaccines at the forefront. So, we might as well go all-in into understanding the little intricacies of how mRNA vaccine encapsulated by lipid nanoparticles (LNPs) might interact with delicate cell types — such as neurons in the brain — that a few experts have raised. Before going further, the conclusion herein is that the actual risk of SARS-CoV-2 infection or Covid-19 largely outweighs the hypothetical risks of the LNP-encapsulated mRNA vaccine. But there are still a few concerns left unanswered, which deserve more transparency. Current vaccines rely on spike protein Nearly all the vaccine candidates for Covid-19 — such as the mRNA, DNA, viral vector, recombinant protein, viral-like particles, and peptide- based vaccines — rely on the SARS-CoV-2 spike protein to induce immunity. > The Pfizer-BioNTech and Moderna mRNA vaccines consist of an mRNA genetic material encased within LNPs that can fuse with muscle and immune cells upon injection. The released mRNA then instructs the cells to make spike proteins, which are expressed on the cell surface to trigger various aspects of the immune system. > The AstraZeneca-Oxford and Johnson & Johnson adenoviral vector vaccines use a harmless modified adenovirus to deliver DNA into the cell to make SARS-CoV-2 spike proteins to induce immunity. > The Novavax peptide-based or protein subunit vaccine uses purified spike proteins of SARS-CoV-2 to induce immunity. >The Sinovac and Sinopharm inactivated vaccines use dead SARS-CoV-2 virions with the spike proteins intact to induce immunity. While these vaccines all rely on the SARS-CoV-2 spike proteins to train the immune system in one way or another, only the mRNA vaccines use the innovative LNP technology to deliver the mRNA into cells. For simplicity, the spike protein mentioned from hereon belongs to SARS-CoV-2, the coronavirus that causes Covid-19. Lipid nanoparticles (LNPs) hypothetical risks The mRNA vaccine is injected intramuscularly through the arm. This method is preferred because large muscle cells have high vascularity, so the injected biomaterial can easily reach the systemic bloodstream and lymphatic system. LNPs fuse with and enter mammalian cells easily. As mentioned, the Pfizer-BioNTech and Moderna mRNA vaccines use LNPs to encapsulate the mRNA genetic material for more efficient cell delivery. Thus, the combined intramuscular injection and LNP technology would enable the mRNA vaccine to reach a broad range of cell types. The mRNA might even reach delicate cells or places that we don’t want them to, such as neurons in the brain or spinal cord. In fact, LNPs are often used to overcome the problem of the BBB blocking medical drugs from entering the brain. Given that the BBB and blood-spinal cord barrier are lipid-soluble, the LNP-encapsulated mRNA vaccine might be able to enter the brain and spinal cord. As a result, brain cells that express the spike protein might be marked as foreign by the immune system. For example, cytotoxic T-cells, which kill virus-infected and cancerous cells, might see the spike protein- expressing brain cells as a threat. Unlike muscle cells and many other cell types, neurons in the brain rarely regenerate. Jacob Wes Ulm, MD, Ph.D., a geneticist, explained this concern in detail in a letter to the British Medical Journal, as well as in a public comment to an article about mRNA vaccines on January 2021: …it seems that they [mRNA vaccines] can enter a much broader tissue range compared to even attenuated virus vaccines…And since the mRNA vaccines would induce SARS-CoV-2 viral spike protein expression, that seems to mean that people who get the mRNA vaccines are going to have a much greater range of cells and tissues vulnerable to cytotoxic [T- cell] attack…with side effects that may not manifest for years (with cumulative damage and chronic inflammation). “This is where the picture gets aggravatingly murky,” Dr. Ulm added, mentioning that there seems to be no comprehensive data on the cellular localization — i.e., which types of cells the biomaterial enters— of the LNPs used by Pfizer-BioNTech and Moderna. Although there have been past studies on the cellular localization of LNPs (more on this below), different LNP formulations would enter different cell types, Dr. Ulm stated, so “we don’t know where in the body they’re going,” adding that: The nightmare scenario would be if e.g. the mRNA vaccines’ lipid nanoparticles are, indeed, crossing the BBB and getting endocytosed into critical glial cells, like oligodendrocytes, or even worse, into neurons themselves in the brain and spinal cord, putting a bullseye on these critical cells for cytotoxic [T-cells].> In fact, one 2017 study vaccinated mice against influenza viruses with LNP- encapsulated mRNA vaccine. While the mRNA vaccine immunizes the mice, the study found traces of the mRNA in the brain at 0.4 ng/ml. However, the amount of mRNA found in the muscle injection site, proximal lymph nodes, distal lymph nodes, and spleen were much larger at 5680, 2120, 117, and 87 ng/ml, respectively. That said, this is also consistent with what the European Medicines Agency’s (EMA) assessment report of the Moderna mRNA vaccine has reported: Low levels of mRNA could be detected in all examined tissues except the kidney [in rats]. This included heart, lung, testis, and also brain tissues, indicating that the mRNA/LNP platform crossed the blood/brain barrier, although to very low levels (2–4% of the plasma level). Therefore, these reports suggest that the LNPs can carry bits of the mRNA vaccine into the brain. But we still don’t know what would happen after the mRNA vaccine enters the brain (more on this below). Notably, for the Pfizer-BioNTech mRNA vaccine, the assessment report by the U.K. government is a bit vague, stating that: Information regarding the potential distribution of the test articles to sites other than the injection site following IM [intramuscular] administration has been provided and is under review as part of the ongoing rolling assessment. Last month, I received an email from Goh Kiang Hua, MD, a consultant general surgeon and Fellow of the Royal College of Surgeons (FRCS), asking if I’ve come across any scientific data on what happens to the cell that makes and expresses the spike proteins upon receiving the mRNA vaccines. I couldn’t find such any, except for the abovementioned EMA’s report that I found posted in an mRNA discussion google group that William Steward, Ph.D., founded. Poster Comment: Don't vax me, bro. Post Comment Private Reply Ignore Thread
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