Копилка научных материалов по вакцинам
Amyloidogenesis of SARS-CoV-2 Spike Protein
SARS-CoV-2 infection is associated with a surprising number of
morbidities. Uncanny similarities with amyloid-disease associated blood
coagulation and fibrinolytic disturbances together with neurologic and
cardiac problems led us to investigate the amyloidogenicity of the
SARS-CoV-2 spike protein (S-protein). Amyloid fibril assays of peptide
library mixtures and theoretical predictions identified seven
amyloidogenic sequences within the S-protein. All seven peptides in
isolation formed aggregates during incubation at 37 °C. Three 20-amino
acid long synthetic spike peptides (sequence 192–211, 601–620,
1166–1185) fulfilled three amyloid fibril criteria: nucleation dependent
polymerization kinetics by ThT, Congo red positivity, and
ultrastructural fibrillar morphology. Full-length folded S-protein did
not form amyloid fibrils, but amyloid-like fibrils with evident
branching were formed during 24 h of S-protein coincubation with the
protease neutrophil elastase (NE) in vitro. NE efficiently
cleaved S-protein, rendering exposure of amyloidogenic segments and
accumulation of the amyloidogenic peptide 194–203, part of the most
amyloidogenic synthetic spike peptide. NE is overexpressed at inflamed
sites of viral infection. Our data propose a molecular mechanism for
potential amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated
by endoproteolysis. The prospective of S-protein amyloidogenesis in
COVID-19 disease associated pathogenesis can be important in
understanding the disease and long COVID-19.
Контекст: др. Коул в видео выше описал амилоидные поствакцинные тромбы. Такие тромбы образуются как после болезни, так и после прививки, ибо триггером является спайк-протеин.
мРНК бустеры ведут к продукции антител класса IgG4, которые позволяют иммунной системе игнорировать коронавирус. Эти антитела появляются в крови после 2 привики и контакта с вирусом, и резко возрастают после бустера. В итоге, после бустера иммунная система толком не борется с вирусом, а принимает его за своего…
RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (IQR) 6.7–18.1%) compared to the overall memory B-cell repertoire (median 1.3%; IQR 0.9–2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
Описанные выше амилоидные тромбы не поддаются растворению обычными средствами, но наттокиназа похоже такой способностью обладает: Amyloid-Degrading Ability of Nattokinase from Bacillus subtilis Natto
Эта способность наттокиназы возможно также понижает риск Альгеймера, растворяя амилоидные бляшки в мозгу.
More than 20 unrelated proteins can form amyloid fibrils in vivo which
are related to various diseases, such as Alzheimer’s disease, prion
disease, and systematic amyloidosis. Amyloid fibrils are an ordered
protein aggregate with a lamellar cross-β structure. Enhancing amyloid
clearance is one of the targets of the therapy of these amyloid-related
diseases. Although there is debate on whether the toxicity is due to
amyloids or their precursors, research on the degradation of amyloids
may help prevent or alleviate these diseases. In this study, we explored
the amyloid-degrading ability of nattokinase, a fibrinolytic
subtilisin-like serine protease, and determined the optimal conditions
for amyloid hydrolysis. This ability is shared by proteinase K and
subtilisin Carlsberg, but not by trypsin or plasmin.
Ещё одно видео с Райаном Коулом: https://thehighwire.com/videos/the-highwires-lab-investiga...
Skewed fate and hematopoiesis of CD34+ HSPCs in umbilical cord blood amid the COVID-19 pandemic
Ковид, и в ещё большей степени вакцинация матери, вызывают апоптоз (программируемая клеточная смерть) гемопоэтических стволовых клеток и падение их уровня в пуповинной крови.
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