The Salk Institute team showed that the spike protein alone can damage vascular endothelial cells by downregulation of ACE-2, inhibition of endothelial nitric oxide synthase (eNOS), impairment of mitochondrial function and direct impairment of endothelial function. Hence, even if one were to change the antigen expressed there would likely still be adverse events. Halma et al. 66 point to the changes made to the mRNA and the ingredients of the lipid-nanoparticles, especially the addition of polyethylene glycol (PEG), that made it both more resistant to degradation and helped it to evade the immune system with lipid-nanoparticles helping biodistribution and bioaccumulation. Biodistribution means that cell death and inflammation could occur in all organs including the brain, placenta, and testes, as has been seen with the COVID-19 mRNA vaccine 5,44,45,46. The gene-based COVID-19 vaccines fall into a special class of therapeutic agents defined by the FDA as \u201cgene therapy products\u201d 36, such that recipient cells produce antigens for transmembrane expression, or to leave the cell, to secondarily invoke an immune response. By design, therefore, by employing virus-like invasion and hijack of cellular transcription, both mRNA and adenovectorDNA gene-based vaccines cause non-immune cells to become de facto antigen-presenting cells, in their mode of immunogenicity.<\/p>\n
Natural messenger RNA is highly unstable, so the synthetic mRNA that codes for spike protein in Moderna and Pfizer COVID-19 vaccines has been stabilised by replacement of uridine with N1-methylpseudouridine 37. This intervention is now known to make the synthetic mRNA excessively stable over a prolonged period 49. Fertig et al. 50 found the lipid-nanoparticle and contained mRNA were still circulating in blood plasma 15 days post-vaccination. Recent research found the mRNA in blood plasma at 28 days post-vaccination 51. Also, the S1 subunit was found recirculating in picomolar amounts along with full spike protein in a Brigham and Women\u2019s Hospital study of 13 nurses vaccinated with the Moderna COVID-19 mRNA vaccine to about 42\u201372 h 52.<\/p>\n
Its ligands, programmed death ligand 1 (PD-L1) and PD-L2, are regularly expressed on antigen-presenting cells like dendritic cells and macrophages; upregulation of PD-L1 is observed after activation of monocytes and granulocytes 233,234. It is too early to make a definitive assessment; however, we can look at the spike protein and its potential to cause cancer or impair the immune system to the point that it cannot fight cancer effectively. In Dalgleish\u2019s letter, he noted the preponderance of these post-COVID-19 vaccine reports were \u201cmelanoma or B-cell based cancers, which are very susceptible to immune control\u201d. The implications of R\u00f6ltgen et al. 53 findings have been elaborated in detail in a blogpost by Jikomes 55 as indicative of danger, whereas a blogpost by Yong 56 argues the prolonged presence of mRNA and spike proteins is not dangerous.<\/p>\n
Afferent vagus nerve fibres, located in nucleus tractus solitarius, provide sensory input to the CNS about the inflammatory status that can result in the transmission of efferent signals, originating from the dorsal motor nucleus, to control the inflammatory response. Such a response is rapid and localised, unlike the diffusible anti-inflammatory network, which is slow, distributed, non-integrated and dependent on concentration gradients 32. The natural course of new pandemic\/epidemic viruses is to become more infectious and less pathogenic with time. In particular, the omicron subvariants have targeted the upper respiratory tract rather than the lower respiratory tract, leading to less systemic penetration of the virus and the spike protein 83.<\/p>\n
This binding model could provide logical explanations for the acute inflammatory disorder and other conditions in patients with COVID-19, long COVID, and vaccination injury, which may be linked to severe dysregulation of the central nervous system. Figure 4, from Wrapp et al. 26, shows one of the three \u2018trimer\u2019 RBDs in green in the \u2018up\u2019 position while the other two RBDs are \u2018down\u2019 and inaccessible to the attachment to ACE-2. The diagram on the left is the view of the spike protein in profile and on the right is a view of the S1 subunit or top of the trimeric spike protein from above. In this context, the Australian State Government (NSW) health data from November and December 2022 21 (Figure 1 and Figure 2) demonstrate that the unvaccinated are almost not represented in the hospitalisation data while the most vaccinated are over-represented. The proportion of unvaccinated in NSW was low at 3.2%; however, the proportion of unvaccinated with severe COVID-19 is lower than this in late 2022 at 2.9%.<\/p>\n
That lipid-nanoparticle biodistribution makes an important contribution to adverse events is further suggested by adverse event reports from the protein-based Novavax COVID-19 vaccine Nuvaxovid. It has the novel technology of a lipid-nanoparticle matrix which could potentially increase biodistribution of the unmodified spike protein, with intact furin cleavage and receptor binding domain sites. In response to a query about biodistribution studies, Novavax replied in mid-2021 that \u201ca pharmacokinetic\/pharmacodynamic study has not been performed on the Novavax COVID-19 vaccine\u201d (personal communication Novavax-Parry, 30 July 2021). Traditional COVID-19 vaccines have not produced the high rates of adverse event reports that characterise the gene-based COVID-19 vaccines.<\/p>\n
As the virus replicates, cell and viral debris or virions may interact with the nAChRs to block the cholinergic anti-inflammatory pathway. If the initial immune response is not enough to combat the viral invasion at an early stage, the extensive and prolonged replication of the virus will eventually disrupt the cholinergic anti-inflammatory pathway and seriously compromise the ability to control and regulate the immune response. The uncontrolled action of pro-inflammatory cytokines will result in the development of cytokine storm, with acute lung injury and acute respiratory distress syndrome (ARDS), coagulation disturbances and multiorgan failure. Based on this hypothesis, COVID-19 appears to eventually become a disease of the nicotinic cholinergic system 92. This, in retrospect, means it has been a particularly poor choice for vaccine development purposes. Even with full protein code expression, some cleavage can still happen inside cells.<\/p>\n
Both the sympathetic (SNS) and parasympathetic nervous system (PSNS) are affected, with the potential for a sympathetic storm and abnormal autonomic responses that include excess sweating, exercise intolerance, insomnia, resting tachycardia, postural hypotension, fatigue, urinary and bowel dysfunction. The neuroinvasive nature of SARS-CoV-2 results in neurological complications such as DSN 96 and suggests either direct autonomic neuronal injury or indirect immune-mediated mechanisms, as would occur with \u03b17 nAChR inhibition. Inhibition of nAChR by SARS-CoV-2 may lead to the inhibition of PSNS and exaggeration of SNS with subsequent progression of cytokine storm 94. These widespread autoimmune and pro-inflammatory effects of spike protein and potentially lipid-nanoparticles illustrate \u2018spikeopathy\u2019 to be another \u2018great mimicker\u2019 akin to tuberculosis, which makes the diagnosis of the underlying aetiology difficult 161. Kelleni reports on the potential risk of vaccines to induce autoimmune diseases such as thrombocytopenia, myocarditis and immune-induced thrombosis and thromboembolism, all potentially fatal and possible causes of sudden death 137. It appears unrelated to the spike protein, and other components of the adenovectorDNA technology are being investigated 132.<\/p>\n
Finally, we reviewed the best autopsy case series currently available, performed in Germany, that establish the connections between spikeopathy and multiple organ failures, neuropathies and death. \u201cYes, that is the finding that we have now been able to collect using special methods. This means that we are actually certain that in this case, we can still detect this toxin in the vessel walls 122 days after the vaccination. Neurological symptoms are commonly noted post-COVID-19, in \u2018long Covid\u2019 and post mRNA vaccination, raising the possibility of prion involvement.<\/p>\n
The underlying pathophysiological and biochemical mechanisms are being elucidated. The lipid-nanoparticle carriers for the mRNA and Novavax vaccines have pathological pro-inflammatory properties as well. The whole premise of gene-based vaccines producing foreign antigens in human tissues is fraught with risks for autoimmune and inflammatory disorders, especially when the distribution is not highly localised. High doses of the toxin-like spike protein binding domain (RBD) inhibit acetylcholine (ACh)-induced \u03b17 nAChR responses.<\/p>\n
This suggests a pathogenic amount of spike proteins from the Novavax COVID-19 vaccine can on occasion reach the heart. Overall, the adverse event reports from the Novavax COVID-19 vaccine are less than from the gene-based vaccines, which would be consistent with a dose-response effect for spike proteins. However, the lipid-nanoparticle matrix itself may be responsible for some of the myocarditis reports. Trougakis et al. 65 reviewing literature on adverse events from COVID-19 mRNA vaccines, noted the risk of spike protein-driven pathology, which they termed the \u201cspike hypothesis\u201d.<\/p>\n
\u201cSARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates\u201d. \u201cThe highest levels of AZD1222 vector DNA (103 to 107 copies\/\u00b5g DNA) were observed beldex coin price today inr<\/a> in the intramuscular administration sites and sciatic nerve (close proximity to the administration sites) on Day 2. Lower levels of AZD1222 vector DNA (4 copies\/\u03bcg DNA) were observed in the bone marrow, liver, spleen and lung on Day 2.<\/p>\n No biological system is 100% effective, and the mutation is only supposed to reduce, not completely prevent cleavage into S1 and S2. The transport of spike proteins or subunits via exosomes, direct cell fusion and nanotube tunnels to other cells is still possible. Expression errors inside the cell could lead to spike proteins retaining certain functions. Contamination with replication-capable plasmid vectors leaves the option of mutation during replication or insertion into the genome. Cancer\u2014although not definitely proven to be caused by the vaccines\u2014seems to follow vaccination closely and we have reviewed possible causes in the form of spike protein interactions with transcription factors and cancer suppressor genes.<\/p>\n","protected":false},"excerpt":{"rendered":" The Salk Institute team showed that the spike protein alone can damage vascular endothelial cells by downregulation of ACE-2, inhibition of endothelial nitric oxide synthase (eNOS), impairment of mitochondrial function and direct impairment of endothelial function. Hence, even if one were to change the antigen expressed there would likely still be adverse events. Halma et… Continue reading SketchUp Make 2017 : Download Links SketchUp SketchUp Community<\/span><\/a><\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[66],"tags":[],"class_list":["post-16875","post","type-post","status-publish","format-standard","hentry","category-cryptocurrency-exchange","entry"],"_links":{"self":[{"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=\/wp\/v2\/posts\/16875","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=16875"}],"version-history":[{"count":1,"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=\/wp\/v2\/posts\/16875\/revisions"}],"predecessor-version":[{"id":16876,"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=\/wp\/v2\/posts\/16875\/revisions\/16876"}],"wp:attachment":[{"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=16875"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=16875"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/manage.busyantmarketing4.a2hosted.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=16875"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}