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CoV–2 Spike Impairs DNA Damage Repair – Inhibits V(D)J Recombination in Vitro
- yellowledbetter 5y agohttps://youtu.be/-SYL-iU0E9Q https://youtu.be/-SYL-iU0E9Q
- TravisDick 5y agoI didn't read the article, but my very basic understanding of mRNA vaccines is that they cause your own cells to produce the spike protein so that your immune system can learn to attack it without actually having the virus present. Does this finding imply that the vaccine would also inhibit DNA damage repair? Or is it more like, in combination with the virus, the spike protein inhibits DNA repair?
- blip54321 5y agoIt does imply that the vaccine would also inhibit DNA damage repair. 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.
- deleted 5y ago[deleted]
- salawat 5y agoHalf-life of mRNA is fairly small, as there is no shortage of enzymes that basically just break it down for recycling. The real problem would have to stem from DNA damage that occurred in the presence of the vaccine that did not either lead to cell death, or get repaired later.
- coldacid 5y ago>The real problem would have to stem from DNA damage that occurred in the presence of the vaccine that did not either lead to cell death, or get repaired later. Which is what it sounds like from the title and abstract.
- didibus 5y agoIt doesn't cause damage it seems, it impairs repair, so it would have prevented DNA repair during the few days the mRNA would have created spike protein. 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.
- boomchinolo78 5y agoHalf-life of mRNA is not small when it is reverse-transcripted. There´s been some misinformation of how mRNA is not reverse-transcripted. mRNA is RNA and all RNA is susceptible of transcription. The messenger part is just a description of it role in a particular process. Sadly, this is the source of many misunderstandings
- TravisDick 5y agoYeah, for context I'm fully vaccinated and not trying to create distrust of the mRNA vaccines. Just curious because that seems like a pretty bad thing. It makes sense that this would only happen while the spike proteins are actually present in your body. Thanks for the response!
- GhettoComputers 5y agoThe mRNA vaccines's mRNA has never been the problem its the adjuvant properties such as the PEG allergies and lipid nanoparticles that have been been causing all the issues. I am sure it will be improved, and they're exploring better adjuvants. When were you vaccinated? If its been a while get your booster. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02183-8/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... 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.
- haimez 5y agoWould anything you’ve learned since your first vaccination make you consider “mixing and matching” for reasons other than supply availability?
- GhettoComputers 5y agoI did not get vaccinated, I was infected and have antibodies. Pfizer has the least amount of foreign bodies, 30ng vs 100ng from Moderna, the JJ can only be used once, so as long as you are upkeeping boosters you will be fine, but the Moderna vaccine with give a stronger immune response. 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-distribution https://protect-public.hhs.gov/pages/therapeutics-distributi...
- meowface 5y agoWhen you say "the vaccine", do you mean the mRNA vaccines specifically, or all of the vaccines?
- revolvingocelot 5y agoIt looks like only the mRNA vaccines. That said, the mRNA vaccines seem better at preventing serious COVID cases for longer, so even if they do screw up one's B and T cells, the serious COVID one might catch once one's J&J runs out will screw them up that much more.
- coldacid 5y agoFrom reading the paper, it'd be all of the vaccines, or at least all that build on the spike protein as the target for our immune systems to focus on.
- deleted 5y ago[deleted]
- coldacid 5y ago[flagged]
- resoluteteeth 5y agoThe virus also produces the spike protein
- coldacid 5y agoAnd that made targeting the spike protein with the vaccines a good idea? No. The spike protein itself is the problem, regardless of its source. The vaccine designers picked a bad target.
- steve_taylor 5y agoThat doesn’t make sense.
- GhettoComputers 5y agoI agree, but the mRNA vaccines factually aren't long lasting. Get your booster if you haven't yet, its important since the protection is about half in under half a year. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02183-8/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
- LurkingPenguin 5y ago> I agree, but the mRNA vaccines factually aren't long lasting. Get your booster if you haven't yet, its important since the protection is about half in under half a year. This is misinformation. From your link: > Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84–96]) up to 6 months. A post regarding a possible "issue" with the vaccines is a strange place to engage in "get your booster!" fearmongering by highlighting VE against infection as compared to the far more important endpoints of hospitalization and death.
- Commodore63 5y agoThe spike protein from the vaccine is injected into your muscle and does not circulate through your system.
- LurkingPenguin 5y agoExcept the researchers raise the possibility that this could be an issue: > 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.
- deleted 5y ago[deleted]
- sethammons 5y agoHow does that explain the cases of myocarditis?
- senectus1 5y agoDr.John Campbell made a very good case about "injection aspiration". https://www.youtube.com/c/Campbellteaching https://www.youtube.com/c/Campbellteaching https://www.youtube.com/watch?v=WuyAtvwP2H4 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.
- vibrato2 5y agothat was the idea, but it turned out not to be true. and then the manufacturers lied about it and covered it up.
- revolvingocelot 5y agoedit: this journal might not be worth paying attention to https://en.wikipedia.org/wiki/MDPI#Controversies https://en.wikipedia.org/wiki/MDPI#Controversies >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.
- j16sdiz 5y agoTLDR: some vaccine maybe safer than other. 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."
- deleted 5y ago[deleted]
- savant_penguin 5y ago"Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA..." Can anyone translate?
- coldacid 5y agoIt hangs around the DNA and makes it hard for the DNA to do its own jobs. Like a really annoying and clueless co-worker.
- jboggan 5y agoThis is an engineering error at its heart. By design the spike protein were supposed to be expressed and embedded in the surface of the cell where they could be recognized by the immune system. Some proportion of them lingering and having any action within the cell was not foreseen.
- kevingadd 5y agoAre you implying that covid-19 was engineered/designed? If not, what are you talking about?
- Consultant32452 5y agoI interpreted it as referring to the spike proteins generated after receiving the mRNA vaccine. They were supposed to have been modified to not be bio-active.
- deleted 5y ago[deleted]
- coldacid 5y agoThe engineering error was on the part of the vaccine designers, choosing the spike protein as the thing to "train" our immune systems without fully understanding what the spike actually does.
- deleted 5y ago
- LurkingPenguin 5y agoThe 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.
- ra 5y agoPlease can someone who is an expert in this field explain this in simple terms for us lay people?
- pas 5y agonot an expert, but you might find this interesting: https://www.youtube.com/watch?v=9E_UxnC_L2o https://www.youtube.com/watch?v=9E_UxnC_L2o 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.)
- jaspergilley 5y agoUser @shusaku refers to MDPI as a "garbage journal". If true, this info should play a bigger part in the discussion here than it currently is
- hlieberman 5y agoThis is published by a predatory publisher (https://en.wikipedia.org/wiki/MDPI#Controversial_articles https://en.wikipedia.org/wiki/MDPI#Controversial_articles). According to homozygoat (https://www.twitch.tv/homozygoat https://www.twitch.tv/homozygoat), it doesn't use real virus (rather, it uses other cells transfected to express some covid proteins), and uses the wrong cell type for the conclusions they try to draw.
- LurkingPenguin 5y agoSo we should ignore everything published by MDPI but take as gospel something stated by a PhD candidate in molecular biology who livestreams on Twitch under the name Homozygoat and has 329 followers there?
- deleted 5y ago[deleted]
- gfodor 5y agoIt depends. If the content in question could possibly cast doubt that the vaccines are anything but 100% safe as drinking a glass of water, then we go with the twitch streamer, NYT journalists, randos on Twitter, etc. If the content in question supports the idea that the vaccines are a silver bullet and must be taken by everyone immediately or they should lose their job and be cast out of public life, then the study involved is now canon and we should label the former groups questioning this as peddling in disinformation.
- modzu 5y agoyour first reference doesn't support your claim
- revolvingocelot 5y agoI think the grandparent comment meant to link https://en.wikipedia.org/wiki/MDPI#Controversies https://en.wikipedia.org/wiki/MDPI#Controversies , which is the heading under which the erroneous link falls. 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 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.
- m0zg 5y agoMethinks we won't really know about the consequences of mRNA (or COVID itself for that matter) until many years later. And currently we're flying blind, and a lot of people are driven by heavily politicized, semi-religious fervor, to the point of giving this stuff to healthy 5 year olds who are not in danger of severe disease at all.
- mc32 5y agoI think it makes sense to vaccinate vulnerable populations. Elderly, and those with comorbidities, however, pre-adolescents I don’t think need it, especially as we don’t know long term effects on the young. For old folks, the reward is well worth any risk. For youngsters given their risk profile, I’m not so sure as we lack information given the trials on youngsters were short and we don’t have long term data.
- m0zg 5y agoExactly my thinking as well. Mandates (and other forms of "encouragement") should be by BMI, age, and comorbidities. I'd be covered by a mandate myself, if one existed: high BMI, (treated) high blood pressure, haven't had COVID (yet, that I know of). That's why I chose to vaccinate myself and that's also why my wife chose to vaccinate. I don't have to do it, I'm self employed, I've done it voluntarily. Moreover, if it were required at the time, in early May, I would not do it at all. Instead we've chosen the most idiotic criteria available - whether or not you work for (or with) the federal government, or whether your employer is woke enough. Google, for example, is woke enough: it even requires vax for _remote_ employees. 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 https://twitter.com/emilyakopp/status/1453136997309198345
- lend000 5y agoThis is one of the more accessible and straightforward microbiology papers I've read. There's no fluff; it tells you how to reproduce and where to buy the materials, and it seems to balance terms in the jargon-heavy field with short explanations, requiring minimal googling to get an overview if you are topically familiar cell biology and chemistry (not to mention VDJ recombination, a fascinating bio-algorithm which should inspire any computer scientist [0]). Compare this to a typical paper where there is an off-putting amount of fluff and then straight into dense unreadable jargon for the rest of the paper. 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). [0] https://en.wikipedia.org/wiki/V(D)J_recombination https://en.wikipedia.org/wiki/V(D)J_recombination
- AstralStorm 5y agoThe implication being that unmodified spike protein and protein producing vaccines could be less effective than some modified ones and also cause a temporary dip in immunity due to locking out some naive B cells, is that correct?
- coldacid 5y agoFrom my reading, possibly more than just a temporary dip for those who have a severe case of COVID-19.
- azth 5y agoWhy was this flagged?