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The key finding: > Our findings provide evidence of the spike protein hijacking the DNA damage repair machinery and adaptive immune machinery in vitro. We prop
by LurkingPenguin 5y ago
The key finding:
> Our findings provide evidence of the spike protein hijacking the DNA damage repair machinery and adaptive immune machinery in vitro. We propose a potential mechanism by which spike proteins may impair adaptive immunity by inhibiting DNA damage repair. Although no evidence has been published that SARS–CoV–2 can infect thymocytes or bone marrow lymphoid cells, our in vitro V(D)J reporter assay shows that the spike protein intensely impeded V(D)J recombination. Consistent with our results, clinical observations also show that the risk of severe illness or death with COVID–19 increases with age, especially older adults who are at the highest risk [22]. This may be because SARS–CoV–2 spike proteins can weaken the DNA repair system of older people and consequently impede V(D)J recombination and adaptive immunity. In contrast, our data provide valuable details on the involvement of spike protein subunits in DNA damage repair, indicating that full–length spike–based vaccines may inhibit the recombination of V(D)J in B cells, which is also consistent with a recent study that a full–length spike–based vaccine induced lower antibody titers compared to the RBD–based vaccine [28].
> This suggests that the use of antigenic epitopes of the spike as a SARS–CoV–2 vaccine might be safer and more efficacious than the full–length spike. Taken together, we identified one of the potentially important mechanisms of SARS–CoV–2 suppression of the host adaptive immune machinery. Furthermore, our findings also imply a potential side effect of the full–length spike–based vaccine. This work will improve the understanding of COVID–19 pathogenesis and provide new strategies for designing more efficient and safer vaccines.
In vitro findings are obviously not as compelling as in vivo findings, but it sounds like this issue is worthy of further investigation. It's a bit disconcerting to learn that the spike protein expressed by vaccines administered to over a billion people might be implicated in the impairment of adaptive immunity.
All mRNA vaccines (Pfizer and Moderna) and the adenovirus vector vaccines (AstraZeneca, J&J, etc.) express the full-length spike protein.
- gmnash 5y agoAccording to the CDC, the mRNA vaccines do NOT induce creation of the full spike: https://www.cdc.gov/vaccines/covid-19/hcp/mrna.html https://www.cdc.gov/vaccines/covid-19/hcp/mrna.html > mRNA vaccines tell our cells to make a piece of the “spike protein” that is found on the surface of the SARS-CoV-2 virus. Since only part of the protein is made, it does not harm the vaccine recipient, but it is antigenic and thus stimulates the immune system to make antibodies.
- LurkingPenguin 5y agohttps://www.nejm.org/doi/full/10.1056/nejmoa2034577 https://www.nejm.org/doi/full/10.1056/nejmoa2034577 > BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. https://www.nature.com/articles/s41541-021-00369-6 https://www.nature.com/articles/s41541-021-00369-6 > The two mRNA vaccines in current widespread application (BioNTech-Pfizer and Moderna) (Table 1) are technologically very similar. They contain codon-optimized sequences for efficient expression of the full-length S protein and use the authentic signal sequence for its biosynthesis44,45,46,47 (Fig. 1b). > The unifying feature of all current adenovirus-vaccine vectors is the replacement of one of the early adenoviral genes (E1) for the full-length SARS-Cov-2 S gene in the adenoviral DNA (Fig. 4a) and the additional deletion of E3 From this post: > To date, many approved SARS–CoV–2 vaccines, such as mRNA vaccines and adenovirus–COVID–19 vaccines, have been developed based on the full–length spike protein If the mRNA and adenovirus vector vaccines weren't expressing the full-length spike, this research would be pointless in the context of the vaccines and the researchers wouldn't raise their findings as a possible efficacy and safety issue for the vaccines.
- Vecr 5y agoThe CDC is obfuscating, or probably lying, depending on your definition. The spike produced from transfected cells is absolutely the whole thing, with two proline insertions, that's it. All the other sequence changes are just optimizations, they don't change the result.
- shusaku 5y ago> … findings are obviously not as compelling…, but it sounds like this issue is worthy of further investigation. That about sums up any article submitted to a garbage MDPI journal.
- nnx 5y agoAren't inactivated virus vaccines (like Sinovac's) also expressing the full-length spike protein?
- pas 5y agoAn inactivated virus does not express anything, it's basically protein debris, and yes, if it's done right it has the full-length spike. But it does not enter cells, it never gets anywhere near DNA.