Messengers of hope: two mRNA Covid-19 vaccines herald a new era for vaccinology
nature.com
nature.com
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..
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.
―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 onset judged by "first contact to health care" was much earlier.
The narcolepsy issue was never going to be uncovered before it was rolled out large scale.
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.
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.
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.
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...
Are you saying introducing other markers as well would make the presence of the spike protein less risky? Why would that be the case?
> What is perhaps most exciting is the potential for mRNA as a rapid and generic platform for any desired immunogen(s). As upstream computational design and downstream processing and manufacture are standardized, custom work will mostly involve optimizing specific mRNA constructs to express efficiently in cells of interest.
It's always interesting to me when we shorten feedback loops like this. For example, could this significantly improve flu vaccines by allowing them to be more up-to-date? How much more quickly can we squash the next pandemic? Could we respond rapidly enough to help with common colds?
One method of approaching a cancer treatment might be to train the immune system to recognize cancer cells as something to be defeated. This on its own isn't new. What's new is the approach toward making a pipeline that can be tested for efficacy/safety/etc. The Bio Eats World podcast linked below has an explainer.
https://en.wikipedia.org/wiki/Messenger_RNA
https://bio-eats-world.simplecast.com/episodes/moderna-covid...
Interesting parallel between the immune system and machine learning - they both need to train and curriculum training (vaccination) is more efficient.
It's almost like machine learning is a form of learning, right? :-D
As I understand it, the answer to both of these questions is likely to be "yes".
https://www.theguardian.com/world/2020/dec/05/team-behind-ox...
Also, in the clinical trials they test the actual produced vaccine, with all errors included.
[1] https://international.neb.com/tools-and-resources/selection-...
RNA has a tendency to accumulate mutations quickly, as evidenced by the many hundreds of variants of SARS-CoV-2 that have already been sequenced (and that's with only ~30,000 bases).
I'll disagree here. Imagine I tell you a white powder of pure molecular composition is made up of just four elements: carbon; hydrogen; nitrogen; and oxygen. Would you ingest it?
It could be strychnine (poison) or glycine (an amino acid). You have no way of knowing.
Likewise, the physiological effects lipid nanoparticles (LNPs) are still mysterious. First, the exact composition isn't known or even revealed in the FDA filing (thus the "most likely" above). Second, even given known composition, there's no way to know how large, how stable, or how aggregated these particles are or what any of that means.
The model for LNPs that gets most widely discussed is an artificial cell membrane. There's a water-filled center surrounded by a bilayer of lipid (grease). These particles may show variable sensitivity to degradation depending on how administered, composition, size, shape, trace impurities, and so on. For example, Moderna's vaccine contains cholesterol, presumably for the same reason our cells do - to modulate membrane fluidity. It's not clear just yet how persistent LNPs might be and what effects they might show, separate from the RNA payload.
You say 'there's no way to know how large, how stable, or how aggregated these particles are or what any of that means', but they have been working with them for years.
Of course they could be lying or hiding information, but it seems like researching them is a way to know things about them.
True - in vitro and in limited human studies. But not at scale in human subjects. That's just this year. Studying this kind of thing is new as far as therapeutics go.
I am not claiming any expertise here - I majored in Biochemistry but never finished (moved to tech). I do have 14 doctors / geneticist / infection disease specialist in my family that share this view.
This seems like a logical leap to me. Yes we need to do something to make us less open to viral threats, but you don’t present any evidence that improved computer simulations can be a useful tool in helping develop/test vaccines faster.
https://en.wikipedia.org/wiki/Computational_biology
https://a16z.com/2020/06/14/folding-at-home-supercomputer-pr...
https://www.hpcwire.com/2020/06/09/supercomputer-research-re...
https://www.ibm.com/blogs/ibm-anz/supercomputing-a-covid-19-...
https://www.cnn.com/2020/03/19/us/fastest-supercomputer-coro...
A simple search will yield months of reading. Just go to an HPC conference like SCinet (https://en.wikipedia.org/wiki/SCinet) and you will see besides energy, nukes and AI biological research is a key use of the computing power.
It also does not really seem to be supported by the evidence that things will never get back to normal if we don't do something radically different. We have a vaccine, there is no indication that we can't just distribute it and put this pandemic to bed.
I was talking with a doctor friend that oversees an ambulatory care group for the county, and they were able to allocate vaccines for the EMTs (first-responders).
Over 50% refused to be vaccinated.
Not sure how we overcome that.
I am especially baffled by the anti-vaccination movement, as I grew up in a world where smallpox and polio had been basically erradicated due to vaccinations as were most of the typical childhood diseases. But where all the victims of those diseases were not forgotten yet. There was no doubt whatever to be vaccinated, I still can remember the polio vaccinations I got in school. And those were ridiculously risky compared to a modern Covid-19 vaccination. But overall the vaccinations saved so many more people than they harmed.
One can only hope that the next months will bring a change. On the one side, there will still be many deaths due to Covid-19, as the death spike follows 4-8 weeks after the infection count spike. On the other side, in two months the effect of the vaccinations should become very visible.
The other concern I have are these cases with mild symptoms, but then becomes a psychotic issue several months later.
It seem to affect a small percentage, but a small percent of a big number can still be a big number.
https://www.nytimes.com/2020/12/28/health/covid-psychosis-me...
Do these folks also refuse to wear masks and gloves when doing their job?
I think there's a substantial difference between wearing PPE and vaccination, both on the employer's side as well as the individual employee's perspectives. Mandating proper use of PPE can never have unintended side effects. No adult has ever died from improper use of an n95 face mask or nitrile gloves. The jury on the new vaccines is going to be out for a while on long term effects. It's not reasonable for an employer to require them yet.
Besides, that would spread the legal burden to the employer were something to go wrong.
- reporting of the initial outbreak in Wuhan was too slow, but still, many countries acted in time.
- whenever a local outbreak of a similar new disease is reported, all countries should immideately go on an alert level, so that when the disease starts to spread, they can act immediately. If efficient reactions had been taken in January, a lot of things had been easier.
- of course watch international travel closely. If you close down flights, close down all travels. It doesn't make sense to ban flights from China, when the virus was coming to the US from Italy. It doesn't make sense to ban EU travellers but allow them to enter relaying via Turkey. Even better: don't ban flight travel, but test on arrival, make a short quarantine mandatory, that is more effective.
- lock down quickly and hard where neccessary, especial with local outbreaks
and the by far biggest elephant in the room:
- better hygene overall. Everyone should own proper masks, FFP2 masks should be stock piled by the government in generous amounts. Going forward, if you have symptoms of any infectious disease, wear a fucking mask! Even if it is the common cold, there is absolutely no justification to spread them to strangers. Even if it is not a deadly pandemic, infectious diseases could be reduced considerably by masks and hand sanitizing/washing. The yearly flu is deadly enough, there are no reasons to let it spread so freely.
I also hope, it becomes the new default to stay at home and work from there, if you have any symptoms. I don't know how many colds is picked up in the office in previous years.
All the involved should be harshly critisized for that.
However this should not be taken as an excuse to deny all good scientific information we have received and the right measures that have been recommended, especially the overly late committment to masks.
At the end of the day, these are all still political animals.
We still don’t have readily available N95 masks for ‘normal’ prices from reputable vendors.
Why they didn't encourage people to just use makeshift masks, is another discussion entirely.
They correctly estimated that compliance with encouragements would be very low (see e.g. current encouragements not to travel to see family at holidays).
If you tell people something that can keep them safe is available on Amazon for $25, all the encouragement in the world isn't going to keep that product from selling out.
I thought he also qualified his statement then that there was no evidence of wide scale community spread yet, but that might have been a different interview.
Regardless, it does highlight how hard it is to communicate with the public about a topic that is dynamic and fast changing.
[1] https://leadstories.com/hoax-alert/2020/05/fact-check-dr-ant...
One more thing towards rules: it really depends on a society agreeing. Like most societies agree that people should wear pants on the street, woman even shirts. There might be people breaking these rules, but overall society managed to make this a very infrequent thing.
How do you know they have less case because people follow the rules ? I have been in Cambodia and Thailand and people don't really follow the rules there and there is barely any case
What would have been easier? Germany reacted quickly and now have a lot of death
> of course watch international travel closely. If you close down flights, close down all travels
How do you close borders like the France - Switzerland that a lot of people cross everyday to go to work?
> lock down quickly and hard where neccessary, especial with local outbreaks
What do you do after the lockdown if you were not able to make it to to 0 cases?
> Going forward, if you have symptoms of any infectious disease, wear a fucking mask
there is still no proof that mask wearing did reduce the transmission of covid
you make it sounds like you have all the answers but that's not that easy
A few comments to the points you noted.
- Germany reacted at the end of February (I am from Germany), which was pretty late considering the international outbreaks, there were quite a few infections in Germany during February. But for the first wave, Germany reacted just in time to avoid a lot of deaths (<10k), but completely failed at preventing the 2nd wave. But even the first lockdown might have been prevented by acting in early february. Carnival was allowed to take place and it was one major outbreak, the other was Ischg in Austria.
- Borders to France and Swizerland had been eventually closed. When it was pretty late. But I was more referring to the US reaction, which banned travel from China only and much later (to late) from Europe, which is still in place, but allow travel via Turkey, which is what all Europeans going to the US are using.
- If you handle local outbreaks quickly, you can get infections down to 0 in the affected region.
- There is plenty of evidence, that masks reduce the transmission of Covid-19, but I was also speaking in a general sense, as I said "any infectious disease". There is no need to spread the cold or flu as quickly as we used to do. As far as I know, since the pandemic, the flu numbers are down a lot, as hygene works.
This is not true for a country like Germany, you would have to hard lockdown for some time and close all borders, and then verify any person who cross the border, and free move in Europe won't make that possible unless all EU countries do it. If you are an island things gets easier in that matter.
The ONLY country which were able to go to zero after a big outbreak is China
This is a good point, since you can't get COVID a second time if you're dead.
Do they test for vaccine innefectiveness corelation with virus lethality and/or complications?
The vaccine trains the body to kill the virus (SARS-Cov-2) when it enters, not deal with the symptoms of the virus using the body to replicate (COVID-19).
Vaccines stop infection.
Therapeutics stop disease.
The map is not the territory.
There are two groups of people. Latent antibody bombs (on slitghest signal antibodies go from zero to hero) and antibody deserts (where even at late stages of desease only low antibody counts are produced). Those which easily make antibodies, kill off the virus quick enough to get significantly less side effects compared to the other group.
IF such model would hold, then it would be natural that antibody deserts dont produce much antibodies when reacting to vaccine, so there would be corellation between succeptible to covid mortality and vaccine innefectiveness.
I wonder who's down voting this and why.
That's why an Emergency Use Authorization is just that - there's an emergency. The FDA is well aware that long term safety is still unclear, but given the circumstances, the risks posed by vaccination for the general public are outweighed by the benefits.
" but given the circumstances, the risks posed by vaccination for the general public are outweighed by the benefits. "
That's the problem, we don't. We don't know what the risk is long term, it is unknown. It is illogical to say that an completely unknown risk has any logical comparison.
This is more uncertainty than the FDA would accept in the usual course of events - but this is an unusual time. The FDA has no adequate, approved, and available alternatives to the emergency authorization when faced with the pandemic. The investigational vaccine appears to be safe and effective against COVID-19 for the general population. Yes, the vaccine poses some unknown risks, but they are very likely vanishingly smaller than the very present health risks posed by the pandemic. For any given individual, they're much more likely to suffer negative health outcomes within the next 5 years from COVID than from the vaccine. Nobody is stating that risk to be zero. But that also doesn't mean "the risk is completely unknown so why even bother?"
How is the emergency authorization any different from an approval? If tomorrow an effective treatment for COVID-19 were to be approved or the pandemic ends, the EUA for the vaccine would be rescinded. Pfizer/Moderna must also track any adverse reactions more closely, and report them to the FDA on an ongoing basis. They also cannot sell them to private players - they're being provided to the FDA & their authorized parties. The vaccines are not licensed for COVID or any other use.
(If we continue at the incredibly slow pace of vaccinations we're going, though, I wouldn't be surprised if experts start recommending people who have had Covid get lower priority. An expert recently shared that, at this rate, it will take ten years to get to herd immunity in the US. [1])
1. https://twitter.com/DrLeanaWen/status/1343920976854196225
I suspect many more doses have been given but not reported (B), and a lot more of the shortfall can be explained by A & C.
If that's true, we're going to be production limited very soon... though the decision to hold back more than half of the doses doesn't help.
Reaching phase 1B will help, too, because it will mean the opening of mass vaccination clinics, which can run in parallel to the remaining portion of 1A which is more targeted and logistically complicated. E.g. Santa Clara County Fairgrounds are set up for high throughput drive-through COVID testing and plans are to use the same infrastructure that can host massive numbers of cars and lanes to have massive numbers vaccinated and waiting out their 20 minute observation time. This site will be able to do thousands of doses per day-- >0.3% of the County's population per day-- alone, which exceeds the number of doses we can be expected to be allocated for quite some time.
Johnson and Johnson is the best hope for another near-term EUA, which could significantly improve vaccine supply in February.
The Oxford vaccine can be stored in a regular refrigerator, which drastically reduces infrastructure cost and makes it speedier to administer, since it doesn’t need to be carefully warmed to room temperature from subzero.
Oh, and it’s cheaper. That matters.
There's no guarantee things would be going any faster, but if anyone can walk into a pharmacy and get a shot it seems like it would speed up a bit.
But how is astrazeneca's methodology reasonable?
https://www.astrazeneca.com/media-centre/press-releases/2020...
>Over 23,000 participants are being assessed following two doses of either a half-dose/full-dose regimen or a regimen of two full doses of AZD1222 or a comparator, meningococcal conjugate vaccine called MenACWY.
The placebo in the study was a meningitis vaccine that actually caused issues that halted the study and because astrazeneca's vaccine was deemed more effective than that, the vaccine was deemed a success.
In what way is that anywhere near a reasonable clinical study?
They will have to do a proper job, if they haven't already. With the other two vaccines already approved, national health boards will be in no rush to fast track it.
It was not considered a failure. There have been some questions about what the best dosage and timing might be for the highest effectiveness, but I've heard the UK may approve it as early as tomorrow.
The USA may wait until the trial being run inside the USA is completed, but that has more to do with ensuring the vaccine is safe and works on their wide demographics than any concerns with how the UK and Brazil studies were done.
The vaccines have lots of side effects. If you give something with lots of side effects and compare it to a placebo with none, people have a good guess of what group they're in and behave differently. This is often considered more reasonable than comparing to a saline injection, and it's a reason why lots of drugs now are compared to e.g. ritalin-- something relatively benign with some side effect that feels like it is "doing something".
The half-dose/full-dose regimen was a mistake in a clinic administering the trial, though. A mistake that happened to look more effective than the overall vaccine population, which is a bit troublesome and a primary reason why AstraZeneca has problems now.
Now that we have effective COVID vaccines, we can run noninferiority trials-- e.g. comparing Moderna's vaccine to a potential new vaccine-- which get around a lot of the problems here.
More on that here: https://news.ycombinator.com/item?id=25548342
Oh, and it's not like the meningitis vaccine will confer any protection from covid.
Edit: And this honest question asking why is too?
There is very little chance you can catch it again if you already,and if you did it is likely to not be severe. But the immunity conferred by vaccines is often stronger and longer lasting from vaccines than from the disease itself. It's likely the case here based on preliminary numbers, but still not fully prove.
You very likely have good enough immunity to wait. Let someone unprotected get the shot.
2) The running theory is that an immunological response is primed by a first infection, so you'll probably benefit little
https://watermark.silverchair.com/ciw066.pdf?token=AQECAHi20...
Better reply: Search the internet for authoritative sources (e.g., official guidance of governmental institutions) or medical guidelines.
https://tkp.at/2020/12/12/meduni-innsbruck-immunitaet-durch-... (German)
If those are the bad side effects of the two vaccines that didn’t make the cut yet, what about the two that did?
This reads too much like a whitepaper / marketing material.
Of course mRNA doesn’t cross the nuclear envelope. It doesn’t mean that it’s not a potential danger to the cells, though.
I’m not anti-vax. But, I don’t want to gloss over the danger with vaccines that were fast-tracked and now will be given to a few billion people.
What could go wrong? Lots, but if we don’t take it, that could be much worse.
It's not just marketing: there was a COVID DNA vaccine competitor and it lost.
1. Moderna only took 2 days to develop this COVID vaccine. [1] That was thanks to major advancements in vaccine development over many, many years. It wasn't just Moderna, other vaccine candidates were developed extra quick too thanks to advancements in science.
2. This vaccine was developed taking advantage of research done on very similar human coronaviruses over decades, starting from SARS in 2002.
3. Most diseases just aren't very prevalent in the population. For instance, if you created an ebola vaccine, there were a total of 14,000 cases globally between 2014 and 2016. Determining the efficacy would take years. On the other hand there have been 82 million cases of COVID since March. 19.2M in the US alone -- that's a prevalence of 5% (!!). It doesn't take long to prove the vaccine works when 1 in 20 people in the US have or have had COVID.
4. Most of the time human and animal trials are done back-to-back to reduce risk. With the government footing the bill and high confidence you can do them both at the same time.
All in all the result is a vaccine much faster but with all the usual rigor.
[1] https://www.businessinsider.com/moderna-designed-coronavirus...
It's not all the usual rigor because vaccines can have side effects that only show up one or more years later, and it's literally impossible to test for such side effects without observing people who've taken the vaccine for at least a year afterwards.
I would turn it around and say unless you have some reason why you would think that this particular vaccine design methodology will lead itself to having longer lead time side effects, a year of study is just fine.
Excellent.
The reason humans range from support of radical change to support of status quo when it comes to the known and unknown is a level of awareness that logic and experience can be defied for a better outcome in some situations.
Our level of scientific understanding during our lifetime may always be as that of those that believed that Earth was generally flat or those that had only just accepted that the Earth revolved around the Sun in what seemed to be a circle; both theories were and still may be held by some as truths, and perhaps to some benefit, but both are widely accepted to be incorrect now.
Fear is the mind-killer, but don’t confuse our innate questioning of what seems best and obvious to some for ignorant lack of acceptance of known truth. We can neither say there is no truth, nor that we know it, until we know it, and the jury is out about who knows it, except for those that believe in it being able to be known by someone.
Even the worst vaccines we have had a defect/side effect rate much lower than that, I think the narcolepsy inducing one did it 1:10000 or even less. And it was narcolepsy, not death.
Bad vaccines seem to be better than Covid by several orders of magnitude...
Of course the likelihood of this happening, and then causing problems in vaccinated individuals are extremely small. Maybe even almost impossible as the mRNAs for the vaccines are heavily modified.
What I mean is if the mRNA vaccine causes antigens that respond to a partial match of c-19 dna segments, which is how it is effective against even yet-to-be-developed spike proteins, isn't it necessarily associated with the hazards of fuzzy matching we have with regexes?
They have no way to access the underlying DNA.
The BioNtech-Vaccine accounts for this afaik, to prevent the spike-proteins from clumping.
So, even further from regex. The RNA gets turned into a sequence of amino acids, which folds in an extremely complex 3D shape, which bind together with two other proteins to form a large structure, the full shape of which is matched by antibodies.
1. https://www.nytimes.com/interactive/2020/health/pfizer-biont...
The vaccine is in no way shape or form a "regex."
"If the mRNA vaccine causes the creation of antibodies which respond to a variety of spike proteins, how can we build confidence around the set of proteins which trigger and don't trigger an immune response, when the set of potential protein configurations is infinite"
I am not trying to mis-represent the problem by using a regex as an example, but trying to describe the "infinite set" aspect of the problem in a way that is understood by 90%+ of the people here.
All vaccines have a risk of allergic reactions. This is why you're supposed to be monitored for at least 10 minutes after the injection. This is especially important for people who have a history of such reactions to vaccines.
[1] Section 6.3.3.2.2.1. in https://www.fda.gov/media/144246/download
[2] Table 23, Ibid.
Your statement is wrong, and I’m glad you welcomed being corrected. Have a nice day.
https://www.cbsnews.com/news/covid-vaccine-pfizer-phase-3-hu...
Two U.S. pharmaceutical giants, Pfizer and Moderna, are in the final phase of coronavirus vaccine development, and Oxford University is expected to start large-scale human trials of its vaccine in the U.S. this month.
This applies not just to any drug you take, but also to the ingredients in the food you eat and the particles in the air we breath. We've come to such realizations before, and we will again.
But we also know for sure that COVID-19 is killing people right now.
There is a small possibility that there could be detrimental effects to a fetus, which is why the vaccines are not currently recommended for pregnant women. It's not expected that there would be a negative effect; it just hasn't yet been tested. (Fortunately pregnancy is not a chronic condition, so people can still be vaccinated after giving birth.)
Do you have sources for those claims?
Now again it is possible that side effects could still be discovered in patients with complicating factors that weren't represented in the trials (like pregnancy or other known or unknown pre-existing conditions). Or just because the effects were too rare to show up significantly in the trials. But again these would be expected to show up quickly as widespread vaccination begins, as did the few severe allergic reactions that have occurred.
Of course as with anything, especially as charged an issue as vaccines, if one goes looking for it one can find plenty of purported evidence that long-term side-effects (by which I mean here side effects that don't show up until long after the vaccine is taken) are possible or even common. But the expert consensus based on the totality of evidence appears to be that this is not a serious concern.
Just to be clear, since this sounds conspiratorial - it is most likely difficult to search because 60 minutes is a copyrighted show and they have an official YT channel but only carries segments of their episodes. So, I suspect it is quite difficult to find any full episode.
https://www.cdc.gov/vaccinesafety/concerns/guillain-barre-sy...
> I recall a famous drug that was given in the 70s and it produced birth malformations.
You’re probably referring to thalidomide.
> What if someone has for XYZ reason more reverse transcriptase than usual? Will his-her DNA be altered?
Highly unlikely since the vaccines don’t code for transposable elements that could integrate into the host genome.
From what I saw, currently there's no recommendation either way for pregnant people; but everyone is watching this group carefully.
My wife and I are trying to conceive and it's such a tough call whether or not she should get vaccinated. I try to read everything, even though I know the answer is "nobody knows." While we wait for more evidence we'll continue to quarantine and stay safe. We're hoping there's a bit more evidence by the time the vaccine is available to us.
The main difference is that the way the mRNA vaccine works is much better understood. Maybe better understood,on a molecular level, than many other medications.
Normal vaccine trials is like normal software testing. Challenge testing is like running dangerous tests in production. Its faster at detecting a problem than normal tests, but ultimately not needed and can blow up badly. The argument for doing it during covid is that time was of the essence and its faster than normal testing procedures. Instead we opted for the safer slower normal testing procedure.
“Even after the vaccine is approved and licensed, regulatory agencies stay involved, continuing to monitor production; inspecting manufacturing facilities; and testing vaccines for potency, safety and purity.
The FDA also monitors adverse events that may occur related to receiving the vaccine, including through its Vaccine Adverse Event Reporting System and Phase 4 clinical trials—optional studies pharmaceutical companies may be required to perform after a vaccine is licensed to continue to monitor safety and effectiveness.” [0]
[0] https://www.jnj.com/innovation/the-5-stages-of-covid-19-vacc...
https://www.pfizer.com/news/press-release/press-release-deta...
https://www.fda.gov/media/144245/download (53 pages)
https://fda.report/media/144673/Moderna+COVID-19+Vaccine+rev... (61 pages)
I think the actual applications had a thousand pages or so, but I haven't found them online.
https://clinicaltrials.gov/ct2/show/NCT04368728 (Pfizer, >40000 participants)
https://clinicaltrials.gov/ct2/show/NCT04470427 (Moderna, 30000 participants)
I'm not talking the mundane details of the logistics of shipping, etc. getting those boxes out. That's well understood. I'm talking strategy of who gets vaccinated, how they find out, how they get in line to receive the vaccine. How government tracks and ensures that the population is getting to an effective level of immunity.
I have not seen a whiff of that information and management system being put in place. We're still random walking our way through this crisis. CVS has more information on the vaccination status of people in the country than the government does, for fuck's sake.
It's almost as if we're leaving it to everyone to figure it out themselves, or on a voluntary basis.
Do you know how you're supposed to get the vaccine? Has anyone contacted you or given you information? Have you seen any information on when you specifically are to sign up to receive the vaccine?
A more contagious/virulent variant of the virus was just detected in Colorado, today. And we're still letting a patchwork of counties figure it out as it comes.
A massive abdication of responsibility / competence by the government.
Just because you have not seen any communication does not mean it is not happening.
In the first stage, yeah, because the employees are mainly healthcare workers.
I'm in Australia and we are slow walking the process instead of using the equivalent of "emergency authorization". That's a risk that our Federal government is taking based on our very low case counts and infection rates.
Whether they roll it out efficiently between themselves and the individual state health authorities is yet to be seen.
Our Federal government has badly failed in its aged care response, which is its responsibility, while complaining loudly about states implementing border controls and other measures based on the economic impact.
Basically, governments that are run by inheritors of the Reaganite/Thatcherite "small government", "states rights" mindset are ignoring the fact that public health does not respect internal borders. This has occurred in the US, the UK, and, to a certain extent, in CA and AU.
The media tried to cover all the how-s, when-s and what-if-s and did okay, and if you google for it you can find a government website with details about the vaccination campaign.
Finding out who's first in line was also easier than expected, that same info website has a link with a list of groups. The gist of it is: medical teams, elderly people, people aged >65, at-risk, then anyone who wants. It's a fairly long list but if you're interested see [1].
Re: signing up, at first it was via phone calls but later on HMOs (health orgs) made it possible to sign up via their apps. Once you sign up it's usually about a week. Some people somehow got an appointment for February but it was moved up to early January very quickly. E.g., my dad.
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[1]: From what I know and can find online now, after medical teams we vaccinated: nursing home caregivers & residents; then anyone over the age of 65 who signs up; then immunosuppressed people (implants etc.); then people with majorly reduced lung capacity; then personal caregivers. Those are all titled "first priority".
"Second priority" is: other risk groups such as diabetes, obesity, serious lung disease, hypertension, etc.; then high-exposure groups such as teachers, prisoners and guards, first responders. After that, anyone who wants to be vaccinated can sign up.
"Priority" also means "wave" at the moment; meaning until we vaccinated all (interested) people aged >65 I, a healthy person <30, can't get the vaccine.
If you push responsibility from the Federal government to the states, each state has to work it out themselves. While the US is a republic of 50 states, there are some times where "states rights" should require them to work co-operatively to establish a standard for all 50 states.
The current administration, throughout the entire pandemic, has abdicated its responsibility to co-ordinate this. The fact that states were forming their own co-operative approaches (see NY/NJ/CT et al) demonstrates the issue.
Basically, the current administration castrated the CDC from performing its function, with political interference in what the CDC did and what the CDC announced.
The current vaccine distribution is effectively "wholesale" with 50 retailers and then the Federal government abdicates any further responsibility.
afaik if you don't know or haven't been contacted you're not on the list yet. You know it's your turn when they tell you it is.
> A more contagious/virulent variant of the virus was just detected in Colorado, today
There are 10 articles a day about new "mutant and more virulent strains" around the world which aren't supported by any evidences
See: https://www.ncbi.nlm.nih.gov/books/n/nap599/ddd00075/#ddd000... and the entire article for the problem.
which is why, in the US, there is a "no-fault" fund: