CoV–2 Spike Impairs DNA Damage Repair – Inhibits V(D)J Recombination in Vitro
mdpi.com
mdpi.com
More to the point that MDPI is a "predatory publisher", however, is this section https://en.wikipedia.org/wiki/MDPI#Inclusion_in_Beall's_list .
The eagle-eyed might point out that Beall removed MDPI from his list of predatory publishers before canning the list entirely, but he singles out MDPI, suggesting that they "tried to be as annoying as possible to the university so that the officials would get so tired of the emails that they would silence me just to make them stop."
I'm not sure we should be engaging so readily with this article.
VDJ recombination is a "random number generator" that helps diversify receptors. (literally it shuffles the a very specific part of the genome of the developing immune cell), which leads to an almost surely new unique receptor that can match previously "undetected pathogens". this makes it possible for the adaptive immune system to have a higher efficiency. (of course if it matches something from the host, it's an autoimmune problem. but there's a step during immune cell development where these misbehaving cells are detected and destroyed, which generally works very well.)
> 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.
> 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.
> 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
> 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.
That about sums up any article submitted to a garbage MDPI journal.
The key takeaway seems to be that not all antibodies are equal, and there are probably on the order of 10^X antibodies that might work well enough to be cured for a specific coronavirus, but these antibody molecules can interact strongly or weakly with other systems in the body. You want one that is a very strong antagonist of the target site on the virus while being as unreactive as possible with everything else. Getting the very best protein on the first try (either via infection or vaccine production) is never guaranteed, but the hope is that it would be good enough and not cause other problems. Also note that you can produce problematic antibodies and T/B cell surface receptors in response to either a vaccine or a virus (see long covid).
Can anyone translate?
I think the key question is timescale. I suspect this would be a short-term side effect, with no real impact. If not -- if it's longitudinal -- it could be scary. I can't imagine how that would happen, though.
Virus would have the same effect, so this isn't an anti-vax argument.
Which is what it sounds like from the title and abstract.
I have no idea how often the body needs to repair DNA and what the effects of not doing it for a few days are though.
Effectiveness against infections declined from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85–97]) but declined to 53% [39–65] after 4 months.
I was waiting for Novavax but they kept delaying it constantly (they said summer, then autumn and now 2022), so I am keeping an eye on Medicago as well, since I think the protein subunit ones are hardier than the mRNA ones. Because the studies keep changing (moderna used to be the best, then they said pfizer was just as protective, then during delta they said JJ was good) its hard to predict what problems and which of the vaccines will be best suited to that environment. The best immunity seems to be from a natural infection so a mild infection that creates antibodies has been said to be the best protective (many self reported infections weren't covid, but the ones that had testing showed very protective long lasting effects), although I don't think that its worth it to risk long covid for this effect.
Despite all this, the monoclonal antibody treatment is very good. It is userful post infection or when you are worried about being exposed, its thousands of dollars per treatment (gov paid for it already and it won't cost you), but its something to keep in mind about its usage. The US is buying a lot of them for treatment you may want to make a note of it around you with this site. https://protect-public.hhs.gov/pages/therapeutics-distributi...
> 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.
https://www.youtube.com/c/Campbellteaching
https://www.youtube.com/watch?v=WuyAtvwP2H4
I personally feel its fairly compelling and I see no harm in performing this extra step to ensure its not being injected directly into a vein.
Not sure why the suggestion was turned down.
>Does this finding imply that the vaccine would also inhibit DNA damage repair?
Well, yes, but consider the context. If you read the article, and it's almost beyond belief that I have to recommend that you read the article in order to discuss it -- indeed, the information that might assuage your fears is in the very first paragraph -- it's been observed that a consequence of surviving a serious case of COVID is that your immune system is fucked, both during and afterward:
>"SARS–CoV–2 infection extraordinarily affects lymphocyte number and function [3,4,5,6]. Compared with mild and moderate survivors, patients with severe COVID–19 manifest a significantly lower number of total T cells, helper T cells, and suppressor T cells [3,4]. Additionally, COVID–19 delays IgG and IgM levels after symptom onset [5,6]. Collectively, these clinical observations suggest that SARS–CoV–2 affects the adaptive immune system."
Searching for a means by which the vaccine might meaningfully damage your adaptive immune system is ill-advised. Frankly, we've got terrifying amounts of information about the deleterious effects of catching and surviving serious COVID, and administration of a vaccine tends to uncontroversially downgrade the seriousness of the COVID infection that you will almost assuredly get eventually. Thus, even if the vaccine harms you in some way, COVID itself will do worse.
That said, the Discussion section does suggest that there may be improvements to full-spike vaccines in future,
>"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."
I'll again point out that however the spike might fuck with B and T cells, the full-blown virus will surely do more.
And that’s the TL;DR folks. Seriously, this distillation makes the choice very easy.
Depends on where you are, the risk of getting inflected varies too.
It is good to stay informed, not blindly take anything you can get.
This sub outsmarts itself so often and it shows. Medical professionals, scientists, researchers, etc are more qualified than I. There’s nothing blind about it.
Explicitly saying nobody should look into a potential negative side effect of vaccines because they might actually find something is down right scary. Much scarier than any fears of “misinformation”. This kind of thinking is why there is mistrust.
You didn't read the article. Or what I wrote about it. The vaccine can't do any worse than the virus, and this study, that does look into a potential negative side effect, found that the virus does indeed do worse!
Scaremongering while putting words into someone else's mouth is why there is mistrust.
I literally quoted your words. Are you suggesting I randomly selected text and copy/pasted it without reading it?
> The vaccine can't do any worse than the virus, and this study, that does look into a potential negative side effect, found that the virus does indeed do worse!
Nothing in what I said implied that the virus could not be and is not worse. It's a more general point that suggesting an angle of research not be attempted because the result might be unflattering regarding vaccines is ill advised.
If an individual is not at risk for serious complications from COVID (e.g. healthy, young, and fit) then it's not irrational to consider the potential side effects of a vaccine v.s. just the risk of the disease itself. Even the comparison to the same types of side effects of an actual infection is not a fair one as that assumes the individual is guaranteed to get sick. Not everyone lives in a city and travels in a sardine can on rails to go to work every morning so the number of human contacts and potential infection points is not uniform.
> Scaremongering while putting words into someone else's mouth is why there is mistrust.
Claiming that quoting someone's own words is "putting words in someone else's mouth" is some fantastic double-think.
North Dakota
Tennessee
Alaska
Wyoming
South Dakota
I don’t believe any of these states even have a single “sardine can on rails” used by daily commuters.
The idea that you are less likely to be infected in rural Wyoming because you commute by car is pure fiction based on the data. Very few people in the United States are able to avoid grocery stores, pharmacies, or restaurants for more than a week or two.
Sure. And the full-blown virus trigger the same immune response and create the same spike protein..
BUT, this is all about risk management. If you live alone in somewhere very low infection rate and don't meet people, there is no point taking this risk.
If you need a vaccine, there are safer (but less effective) alternative vaccines.
Heh, good luck! Delta's r0 of 6 to 8 is too high to meaningfully avoid. Sure, if you're some sort of hermit, you can probably manage, but if you're in North America, vaccination rates in rural areas will work against you. Frankly, there's no point in taking the risk.
This article calls out "full–length spike–based vaccine".
"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"
"This work will improve the understanding of COVID–19 pathogenesis and provide new strategies for designing more efficient and safer vaccines."
Another utterly idiotic thing is that we're not considering 190 million people who are already immune by having had COVID.
For kids or healthy younger adults, looking at the stats, I just don't see the need at all. Feel free to persuade me otherwise, but with data, not sermons or "mandates".
My 17 y/o son who is healthy, and has no comorbidities, won't be getting the vaccine unless he himself decides to get it. I told him we will support him whichever way he chooses, but if he is harmed by vaccintation, he will have no legal recourse, which is true. I'm not sure he understands what that means. For us that could mean up to several hundred thousand dollars in hospital costs, and potentially the loss of the only child.
I just don't think a little over 2800 kids in the 5-11 y/o trial, _none of which got severe disease_ is a sufficient indication of anything, let alone long term safety. Sounds to me like the only person who abstained from the FDA vote [1] concurs, and the rest just don't have the balls to say what needs to be said. They literally said "we won't know if it's safe until we start giving it". I'm sorry, I'm not willing to take that chance. That's for kids 5-11, but I think the reasoning holds for young adults as well. I didn't raise him for 17 years just so someone at Pfizer could make 30 bucks by giving him myocarditis with zero legal consequences.
[1] https://twitter.com/emilyakopp/status/1453136997309198345
The second most vulnerable elderly people are prime candidates for vaccination though. They’re not as old, more healthy and less likely to have complications from the vaccine. It can be very dangerous for very old or sickly people and those are the people that others vaccinate for so they don’t get it themselves.
The heart problems aren’t common but I didn’t get vaccinated myself, I was waiting for the novavax which they kept delaying. Hopefully by next year it’ll be released, I’ll be first in line since it doesn’t have the same issues that concern me about mRNA or adenovirus.
I'm not convinced this is true. As far as I can tell after looking at the data (as thoroughly fucked up and obfuscated as it is) the vaccine is well tolerated in the elderly. Certainly much better tolerated than COVID itself, especially for people 65 and over.
That's like saying "chemicals are safe". I'm pretty sure the same folks who created the Moderna vaccine could just as well cook up a doomsday military grade pathogen using the same equipment and technology, over approximately the same period of time (a weekend).
I'm not saying vax is not safe. Its safety record, while not perfect, is relatively well understood in adults (but wasn't at the outset). I'm merely saying it's a risk, that should be weighed against the benefits, which (IMO) significantly outweigh the risks for me personally, but not necessarily for someone younger or healthier.