―https://en.wikipedia.org/wiki/Cross-reactivity#Applications_...
EDIT: The mRNA vaccines are obviously not therapeutic antibodies, but they probably checked for cross-reactivity of the engineered spike protein as well as the generated antibodies using similar methods. I’m not 100% sure, though.
There is a study[0] showing cross-reactivity between SARS-CoV-2 antibodies and other human tissues, thus predisposing the host to autoimmune diseases. This should apply even more so to any vaccine since vaccines produce a more robust immune response.
Phase 2/3 of Pfizer-BioNTech did, however, include people with autoimmune diseases [1]. Other vaccine trials did not, as far as I am aware. This does not really shine a light on pre-disposition to an autoimmune disease 6-9-12 mo down the road.
Reading this comment again before I post made me realize it sounds very gloomy, so I feel obliged to say I'll be getting whatever vaccine I can get my hands on at the soonest possible date.
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246018/#__ffn_...
> There is a study[0] showing cross-reactivity between SARS-CoV-2 antibodies and other human tissues, thus predisposing the host to autoimmune diseases. This should apply even more so to any vaccine since vaccines produce a more robust immune response.
Since the antibody tested in the study was a commercial, monoclonal one, this is somewhat hard to assess. But I think you’re right given what they found in the blood tests.
> This does not really shine a light on pre-disposition to an autoimmune disease 6-9-12 mo down the road.
Autoimmune reactions should happen in the short run, right?
I believe Pandermix took 6 months for narcolepsy to develop.
The narcolepsy issue was never going to be uncovered before it was rolled out large scale.
the onset judged by "first contact to health care" was much earlier.
It is at this point that I remind myself of all the other dangerous things that I do: driving, motorcycling, rock climbing, skiing, etc.
The risk of long term side effects is worth the benefit of spinning up the global economy again.
I think the answer to this questions would be nice to have.
"Several vaccine candidates are expected to induce the formation of humoral antibodies against spike proteins of SARS-CoV-2. Syncytin-1 (see Gallaher, B., “Response to nCoV2019 Against Backdrop of Endogenous Retroviruses” - http://virological.org/t/response-to-ncov2019- against-backdrop-of-endogenous-retroviruses/396), which is derived from human endogenous retroviruses (HERV) and is responsible for the development of a placenta in mammals and humans and is therefore an essential prerequisite for a successful pregnancy, is also found in homologous form in the spike proteins of SARS viruses. There is no indication whether antibodies against spike proteins of SARS viruses would also act like anti-Syncytin-1 antibodies. However, if this were to be the case this would then also prevent the formation of a placenta which would result in vaccinated women essentially becoming infertile. To my knowledge, Pfizer/BioNTech has yet to release any samples of written materials provided to patients, so it is unclear what, if any, information regarding (potential) fertility-specific risks caused by antibodies is included."
> Jacob Yount, an associate professor of the department of microbial infection and immunity at Ohio State University, College of Medicine, has studied the syncytin proteins as well as SARS-CoV-2. Yount said the COVID vaccines do not contain syncytin-1 protein or mRNA encoding syncytin-1, and thus there is no reason to think that an immune response against syncytin-1 would be developed.
> “We don’t see infertility with the flu vaccine and that is also targeting a viral fusion protein in a similar way that the spike is a viral fusion protein of the coronavirus,” he said.
This professor doesn't know about how much of the sequence is copied. He doesn't know the widespread affect of mRNA vaccines because we're in new territory here and it's possible that the risk of autoimmune responses is higher with such vaccines. He should know better than to equate mRNA vaccines with more traditional vaccines.
With every vaccine, a small percentage of people suffer adverse and autoimmune effects.
As that professor well knows, we're NOT discussing possibility (with that billions of people lined up, it's all but inevitable). Instead, we're discussing PROBABILITY that it will happen and how many people will be adversely affected.
I'm not saying the vaccine is bad or that people should freak out and not get vaccinated (even some vaccines with high complication rates have historically been much more helpful than harmful). I'm pointing out that while the intentions of the professor may be good, they're definitely not speaking the absolute truth and aren't actually in a position to know all the actual details about the vaccine.
My understanding is that, yes, the proteins are similar, but not the same, and that a similar protein also exists in influenza which does not cause infertility when targeted by our antibodies. I assume this doesn't mean that it couldn't cause infertility in the case of a COVID-19 vaccine, but it would suggest it's perhaps unlikely.
Is there any reason to believe an mRNA vaccine would be anymore likely to cause our antibodies to target the syncytin-1 spike protein as opposed to a more traditional vaccine?
I do agree with your point that it's more a question of the probability of side effects than a possibility. This is something that's bothered me about the attacks on those who are hesitant on the safety of these vaccines. Although I'm sure there's a very low risk that someone will suffer any adverse effects from these vaccines there is almost certainly going to be some cases of adverse side effects, so in the interest of public trust in the COVID-19 vaccines and all future vaccines we should be ensuring the public understand the risks fully and not attacking anyone for asking questions or expressing doubts, because if it does turn out that some of those doubts did indeed hold merit then no one will trust a word the media or professors have to say on this in the future.
We also don’t fully understand what causes autoimmune disease, but various environmental causes have been explored including bacterial and viral infections. Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus.
Unfortunately the incentives in our medical system are not designed to find cures for autoimmune diseases, although they are very much incentivized for palliative care, so progress has been painfully slow in understanding the deeper complexities of the immune system.
This is true. Some of the extremely rare auto-immune issues that have impacted people who have been vaccinated for specific flu viruses in, IIRC, 1976 and 2009, were thought to occur at even higher rates and severity with people who contracted the virus. So, vaccination might impact you, but likely worse the the virus itself due to the greater amount of virus in your system.
I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.
This is the angle that, for me, is suppressing my innate concern for a widescale and rapid application of a brand new immunological therapy. It's extremely targeted and feels like the future. I can imagine a day where the FDA approves the process rather than the instance of mRNA-based therapies, allowing for highly personalized treatment.
This was recently noted in a AMA by virus experts on reddit.
Sure, but aren't the proteins produced by the vaccine virtually identical to the ones produced by the actual virus?
If so, the calculus looks like this:
1) Take the vaccine and accept the (unknown, but apparently quite small) probability that something in your body will react very negatively to the generated viral proteins.
2) Get the virus, accept the probability (also unknown, but the same as in 1) that something in your body will react very negatively to the viral proteins, plus accept the additional risk of being infected by the actual virus.
I guess the third possibility would be to refuse the vaccine and gamble that you won't get the virus, either.
If that's generally true, the difference here would be that the part of the spike protein topology that is typically bound to other proteins in an actual infection would be accessible to the immune system in the case of a vaccination. I think that is where the differential risk could occur with a vaccination that wouldn't occur with an actual infection (however small that might be).
In my daughter's case, something happened when she was about 14 years old that caused her body to determine that the beta cells in her pancreas were invaders and have to die, so I'm just tuned into this kind of possible side effect.
If the virus is destroyed and released into the extracellular environment, its proteins can dissociate and are further fragmented and processed by the immune system. What’s usually presented to T cells are small antigen pieces as opposed to the whole virus/protein.
Virus takes over the cell, makes the cell to manufacture components of the virus and to assemble viruses, until this disrupts the cell so bad that the cell dies and typically bursts. Surely at this point, not only assembled viruses, but also components at different stages of production, are released?
https://en.wikipedia.org/wiki/Introduction_to_viruses#Life-c...
OT, but what does this mean or refer to? I'm curious :)
Corny but fun, they had a few good ones.
I was wrong, its the nucleocapsid protein, not the membrane one, but that's even weirder as the N protein is only found inside the virus particle..
Are you saying introducing other markers as well would make the presence of the spike protein less risky? Why would that be the case?
Reading https://theconversation.com/what-is-the-ace2-receptor-how-is...
there is a section that explains the difference between ACE-1 inhibitors (like in ramipril etc) and ACE-2 inhibitors.
Wikipedia has the layman's details of the RAAS system:
https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_syst...
The very end of mRNA is polyadenylated. This is a fancy way of saying it ends on a lot of AAAAAAAAAAAAAAAAAAA. Even mRNA has had enough of 2020 it appears.
mRNA can be reused many times, but as this happens, it also loses some of the A’s at the end. Once the A’s run out, the mRNA is no longer functional and gets discarded. In this way, the ‘poly-A’ tail is protection from degradation.
Studies have been done to find out what the optimal number of A’s at the end is for mRNA vaccines. I read in the open literature that this peaked at 120 or so.
The BNT162b2 vaccine ends with:
UAGCAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAGCAUAU GACUAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAA
This is 30 A’s, then a “10 nucleotide linker” (GCAUAUGACU), followed by another 70 A’s.
The mRNA isn't intended to be copied in the body. Once the dose is used up there should be no more spike proteins created.
Here is a study of the effects - https://www.nejm.org/doi/full/10.1056/NEJMoa2024671.
It doesn't directly address your question, but it does show how the vaccine performs to control (labeled pbs) in terms of viral load and immune system activity when challenged with a dose of the virus.
The two shots have nothing to do with mRNA stability, they improve immunity, as in any other vaccine given in two or three shots.