COVID-19 RNA Based Vaccines and the Risk of Prion Disease
https://www.researchgate.net/publication/352148028_COVID-19_RNA_Based_Vaccines_and_the_Risk_of_Prion_Disease
https://scivisionpub.com/pdfs/covid19-rna-based-vaccines-and-the-risk-of-prion-disease-1503.pdf
Prions are misfolded proteins with the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals
Mode of transmission
Scientists believe CWD proteins (prions) likely spread between animals through body fluids like feces, saliva, blood, or urine, either through direct contact or indirectly through environmental contamination of soil, food or water.
Prion disease
Microscopic "holes" are characteristic in prion-affected tissue sections, causing the tissue to develop a "spongy" architecture
Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloids, which disrupt the normal tissue structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the vacuole formation in the neurons. Other histological changes include astrogliosis and the absence of an inflammatory reaction. While the incubation period for prion diseases is generally quite long, once symptoms appear the disease progresses rapidly, leading to brain damage and death.[21] Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes.
In humans:
Creutzfeldt-Jakob disease (CJD) and its varieties: iatrogenic Creutzfeldt-Jakob disease (iCJD), variant Creutzfeldt-Jakob disease (vCJD), familial Creutzfeldt-Jakob disease (fCJD), and sporadic Creutzfeldt-Jakob disease (sCJD)
Gerstmann-Sträussler-Scheinker syndrome (GSS)
Fatal familial insomnia (fFI)
Sporadic fatal insomnia (sFI)
Kuru
All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal. However, a vaccine has been developed in mice that may provide insight into providing a vaccine in humans to resist prion infections. Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production - thus theoretically making them immune to BSE, building on research indicating that mice lacking normally-occurring prion protein are resistant to infection by scrapie prion protein.
Protein-only hypothesis
Prior to the discovery of prions, it was thought that all pathogens used nucleic acids to direct their replication. The "protein-only hypothesis" states that a protein structure can replicate without the use of nucleic acid. This was initially controversial as it contradicts the so-called "central dogma of molecular biology," which describes nucleic acid as the central form of replicative information.
Evidence in favor of a protein-only hypothesis include
No virus particles have been conclusively associated with prion diseases
No nucleic acid has been conclusively associated with infectivity; agent is resistant to degradation by nucleases
No immune response to infection
PrPSc experimentally transmitted between one species and another results in PrPSc with the amino-acid sequence of the recipient species, suggesting that replication of the donor agent does not occur
Level of infectivity is associated with levels of PrPSc
PrPSc and PrPC do not differ in amino-acid sequence, therefore a PrPSc-specific nucleic acid is a redundant concept
Familial prion disease occurs in families with a mutation in the PrP gene, and mice with PrP mutations develop prion disease despite controlled conditions where transmission is prevented.
Alpha to Beta Sheet Conversion
Probing the N-terminal β-sheet conversion in the crystal structure of the human prion protein bound to a nanobody.
https://pubmed.ncbi.nlm.nih.gov/24400836/
