New SARS-Cov-2 mRNA vaccination study
Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs
https://www.sciencedirect.com/science/article...152200206X
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Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs
Quote:Highlights
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mRNA vaccines promote sustained synthesis of the SARS-CoV-2 spike protein.
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The spike protein is neurotoxic, and it impairs DNA repair mechanisms.
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Suppression of type I interferon responses results in impaired innate immunity.
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The mRNA vaccines potentially cause increased risk to infectious diseases and cancer.
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Codon optimization results in G-rich mRNA that has unpredictable complex effects.
Quote:The increasing evidence that the vaccines do little to control disease spread and that their effectiveness wanes over time make it even more imperative to assess the degree to which the vaccines might cause harm. That SARS-CoV-2 modified spike protein mRNA vaccinations have biological impacts is without question. Here we attempt to distinguish those impacts from natural infection, and establish a mechanistic framework linking those unique biological impacts to pathologies now associated with vaccination. We recognize that the causal links between biological effects initiated by mRNA vaccination and adverse outcomes have not been established in the large majority of cases .
Quote:8. Impaired DNA repair and adaptive immunity
The immune system and the DNA repair system are the two primary systems that higher organisms rely on for defense against diverse threats, and they share common elements. Loss of function of key DNA repair proteins leads to defects in repair that inhibit the production of functional B- and T-cells, resulting in immunodeficiency. Non-homologous end joining (NHEJ) repair plays a critical role in lymphocyte-specific V(D)J recombination, which is essential for producing the highly diverse repertoire of B-cell antibodies in response to antigen exposure (Jiang and Mei, 2021). Impaired DNA repair is also a direct pathway towards cancer.
A paper published by Liu et al., in 2021 monitored several parameters associated with immune function in a cohort of patients by conducting single-cell mRNA sequencing of peripheral blood mononuclear cells (PBMCs) harvested from the patients before and 28 days after the first injection of a COVID-19 vaccine based on a weakened version of the virus (Liu et al., 2021). While these vaccines are different from the mRNA vaccines, they also work by injecting the contents of the vaccine into the deltoid muscle, bypassing the mucosal and vascular barriers. The authors found consistent alteration of gene expression following vaccination in many different immune cell types. Observed increases in NF-κB signaling and reduced type I IFN responses were further confirmed by biological assays. Consistent with other studies, they found that STAT2 and IRF7 were significantly downregulated 28 days after vaccination, indicative of impaired type I IFN responses. They wrote: “Together, these data suggested that after vaccination, at least by day 28, other than generation of neutralizing antibodies, people's immune systems, including those of lymphocytes and monocytes, were perhaps in a more vulnerable state. ” (Liu et al., 2021).
These authors also identified disturbing changes in gene expression that would imply impaired ability to repair DNA. Up to 60% of the total transcriptional activity in growing cells involves the transcription of ribosomal DNA (rDNA) to produce ribosomal RNA (rRNA). The enzyme that transcribes ribosomal DNA into RNA is RNA polymerase I (Pol I). Pol I also monitors rDNA integrity and influences cell survival (Kakarougkas et al., 2013). During transcription, RNA polymerases (RNAPs) actively scan DNA to find bulky lesions (double-strand breaks) and trigger their repair. In growing eukaryotic cells, most transcription involves synthesis of ribosomal RNA by Pol I. Thus, Pol I promotes survival following DNA damage (Kakarougkas et al., 2013). Many of the downregulated genes identified by Liu et al. (2021) were linked to the cell cycle, telomere maintenance, and both promoter opening and transcription of POL I, indicative of impaired DNA repair processes.
One of the gene sets that were suppressed was due to “deposition of new CENPA [centromere protein A] containing nucleosomes at the centromere.” Newly synthesized CENPA is deposited in nucleosomes at the centromere during late telophase/early G1 phase of the cell cycle. This points to arrest of the cell cycle in G1 phase as a characteristic feature of the response to the inactivated SARS-CoV-2 vaccine. Arrest of pluripotent embryonic stem cells in the G1 phase (prior to replication initiation) would result in impaired self-renewal and maintenance of pluripotency (Choi et al., 2013).
Two checkpoint proteins crucially involved in DNA repair and adaptive immunity are BRCA1 and 53BP1, which facilitate both homologous recombination (HR) and NHEJ, the two primary repair processes (Zhang and Powell, 2005; Panier and Boulton, 2014). In an in vitro experiment on human cells, the SARS-CoV-2 full-length spike glycoprotein was specifically shown to enter the nucleus and hinder the recruitment of these two repair proteins to the site of a double-strand break (Jiang and Mei, 2021). The authors summarized their findings by saying, “Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site.”
Another mechanism by which the mRNA vaccines could interfere with DNA repair is through miR-148. This microRNA has been shown to downregulate HR in the G1 phase of the cell cycle (Choi et al., 2014). As was mentioned earlier in this paper, this was one of the two microRNAs found in exosomes released by human cells following SARS-CoV-2 spike glycoprotein synthesis in the experiments by Mishra and Banerjea (2021).
https://www.sciencedirect.com/science/article...152200206X
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#Vaccine
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