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Am I crazy for being nervous about taking an mRNA COVID shot? Like all of you I’m not an expert in the field, but from what I’ve skimmed online it seems like m

Am I crazy for being nervous about taking an mRNA COVID shot? Like all of you I’m not an expert in the field, but from what I’ve skimmed online it seems like mRNA vaccines have never been used widespread in humans before? This is making me want to take the J&J one instead. I’m totally open to other opinions though, I haven’t made up my mind on this.

colinmcd 6y ago
I'm no biologist, but mRNA is ephemeral by design - it's constantly being broken down in the body. The fact that mRNA is converted to proteins by ribosomes is one of the best understood processes in cellular biology, and synthesizing the mRNA for a new protein is not a new idea. Getting actual viral vectors injected into my arm seems much more concerning on the surface (though it's obviously also very safe).
- yasp 6y ago
  Were that it was so simple. My understanding is the mRNA used in the vaccines was engineered to be more stable (less ephemeral). Not sure what that means in terms of half life, but AFAICT it's a mistake to assume that it will behave similarly to naturally occurring mRNA if this is true.
  - pkaye 6y ago
    They put a lipid coating around the mRNA to protect it. But as soon as that coating is removed, it will be quickly be broken down in the body by various enzymes.
    - yasp 6y ago
      How long does the coating take to be removed? Can the mRNA still be (reverse-)transcribed while in the presence of this coating?
      - pkaye 6y ago
        I'm no expert on this but the lipid coating allows it to enter the cell where the coating is removed and the reverse transcription happens. I've read that any of the mRNA that is injected will be gone within 2-3 in the body.
        primozk 6y ago
        2-3 what?
        pkaye 6y ago
        days
      - kolinko 6y ago
        If it can be reverse transcribed then so can Covid which has the same mRNA as the vaccine and way way more. Plus, covid infects a million times more cells than the mRNA vaccine.
    - lima 6y ago
      But they also modified the mRNA structure to make it more durable (but still on the order of days/weeks).
  - roofwellhams 6y ago
    I agree, if you ever did any software you know perfectly that just adding something might have side effects even if it's 99% the same. There is a risk imo.
detaro 6y ago
One major argument is that the mRNA-part is the initial delivery vehicle that does not stay around, so if it being mRNA-vaccine would cause issues we'd very likely know by now. That said, given that the mRNA-vaccines are used for everybody there is little reason why you shouldn't be able to get J&J if you are more comfortable with that.
shock-value 6y ago
You aren't crazy of course, but all indications are they are quite safe. Additionally, a lot of the excitement around mRNA techniques in general is that it is actually a much "lighter touch" than others in various ways -- e.g. not editing genes like CRISPR, using a much simpler delivery method (lipid delivery vehicle vs adenovirus delivery as in the other vaccines), etc.
Symmetry 6y ago
I'm generally more sanguine with mRNA vaccines than other sorts. The problems we've historically had with vaccines have mostly either been with live attenuated viruses that turned out to not be attenuated enough or with adjuvants. With mRNA there's no virus at all and it works via the normal cell viral infection detection pathways so no need for an adjuvant that might accidentally sensitize you to something else.
dnautics 6y ago
> Like all of you I’m not an expert in the field, but from what I’ve skimmed online it seems like mRNA vaccines have never been used widespread in humans before? Moreover there haven't been any long-term studies... There is a very very small chance that something strange happens [0]. > Am I crazy for being nervous about taking an mRNA COVID shot? You're not crazy, but you're probably being unreasonable. The "gut-feeling" likelihood of something strange happening are very very low. [0] one mRNA-specific example, and one "new investigational drug" example: 1. the mRNA could somehow retrotranspose into your DNA, and cause problems. It's not seen in the lab but that doesn't mean it doesn't happen in vivo, it could also depend on what active retrotranspons you have inside of your cells. 2. the antigen could accidentally elicit an antibody response that activates an oncogenic receptor and increase your chances of getting cancer. I think it's important to note that these are plausible mechanisms and are probably untested/untestable at the scales that matter when you're delivering to millions of people. But plausible does not mean significant. Every time you put something in your body, whatever it is, if it's food from the grocery or that new whiskey that hit the market, you're taking on risk. And keep in mind how convoluted a mechanism it takes to get to the point where it's something risky.
- fokinsean 6y ago
  I recently came across this study which suggests it can retrotranspose into your DNA. From what I understand they weren't attempting to find that intentionally, but found it while looking into why people were testing positive for COVID many months after being infected and not currently infected. I'm not suggesting that the vaccines could do the same, but it's not that big of a leap to wonder if the virus can retranspose, then the vaccine could as well. Also I'm aware it's a preprint and not fully peer-reviewed yet, interesting nonetheless. https://pubmed.ncbi.nlm.nih.gov/33330870/ https://pubmed.ncbi.nlm.nih.gov/33330870/
- e_y_ 6y ago
  Absent the cell already being cancerous, wouldn't it eventually die off or become targeted by the immune system (I'm not sure if the synthesized spike proteins are free-floating or if the cell becomes some kind of sacrifice for the immune system to kill and dissect)?
seriousquestion 6y ago
You have to weigh the risk reward for your particular situation. Are you more nervous about a new vaccine or Covid? It depends on your age and comorbidities.
- outworlder 6y ago
  It doesn't depend on age or comorbidities. Covid vaccines - of any type - are orders of magnitude safer than getting infected by a "live" and constantly mutating virus.
bialpio 6y ago
What dispersed all of the fear for me was reading this: https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source... Especially the part about poly-A tail. IIUC, it means that each mRNA "particle" that gets delivered into your body has an upper limit on how many times the protein will get synthesized from it, and the payload only contains info on the spike protein, so there should be no runaway synthesis of something else that would take over my entire body. Standard disclosure: IANADoctor. Also, got my first shot 3 days ago.
- roofwellhams 6y ago
  But that's just theory... It's not guaranteed to happen in practice, right?
- thehappypm 6y ago
  This is an excellent article. Thank you for sharing. This whole pandemic I've been waiting for us to "get lucky" and find that the virus has some weakness. Like some simple off-the-shelf medicine is a cure. Or that it spreads through some simple mechanism we can beat easily. Or that it can't handle summer. Or that it would never mutate. Nothing seemed to go our way though. Then the mRNA vaccines came and that was finally our lucky break! Now thanks to this article I can see that the real breakthroughs came years earlier, from basic researchers. Without these breakthroughs -- which I'm sure didn't excite the public or earn anyone a Nobel prize -- we'd have only inferior vaccines out there.
stopping 6y ago
FYI: The J&J vaccine directly injects DNA into the cell nucleus to begin spike protein production. DNA-based vaccines have been tested before (see J&J's Ebola vaccine), and I believe the general consensus is that mRNA is a safer technology due to its inherently short lifetime.
- outworlder 6y ago
  Indirectly! It uses an adenovirus as the vector to do so.
trashface 6y ago
I got J&J and am currently waiting around to see if I get a blood clot. Hope I recognize the symptoms. I have a lot of weird aches normally so I might miss it. Hopefully can avoid a multiple-thousand dollar trip to the ER just to find out its nothing. Yes I understand the risk is low, but its higher than the one in a million number everyone is throwing around. Potentially much higher as I suspect that cases in men haven't been reported.
- marvin 6y ago
  Even if you believe Norway's numbers to be close to your average, it's ~1:20,000. So the odds are still quite safe, and it's thankfully cureable if discovered early.
  - trashface 6y ago
    I tell myself this every night when my leg is hurting.
    - marvin 6y ago
      Isn't there a telltale sign with miniature bruises/bleedings in the skin? I think the doctors involved in the study made a list. I'm assuming you've looked at it?
      - trashface 6y ago
        You're right I don't have any of that. And leg is feeling better. I'm probably fine and should stop worrying.
  - ostenning 6y ago
    What? That number is huge!
    - marvin 6y ago
      Well, now you know why Denmark and Norway suspended AZ vaccinations for everyone, and many European countries stopped them for everyone younger than 65. It wasn’t because their governments are antivaxxers.
marvin 6y ago
I've been thinking the same things, that there is a small likelihood there's a nasty black swan hiding in there somewhere. But in addition to the theory, we're approaching one year of empirical data on large-scale clinical trials, soon improving by the millions every day. So I'm less and less nervous for such a "holy shit, who could have imagined that" moment for each week that passes. That the rare AZ/J&J side effects were promptly discovered is also a good sign that the monitoring system works.
ycombinete 6y ago
I went with Sinopharm, even though I did have the choice to take Pfizer. I prefer the idea of a traditional vaccine. I’ll see how MRNA looks after this mass beta testing is complete.
outworlder 6y ago
> This is making me want to take the J&J one instead. On one hand, we have mRNA, which is self-limiting and that we know exactly what it encodes, as every single base has been put in there by us. We know what protein it encodes. And if that protein turns out to be harmful long term, guess what, the virus has it too. On the other hand, we have a viral vector vaccine, which injects a live adenovirus which then delivers the instructions? I know we have chosen a harmless virus, but it's an entire virus nonetheless. mRNA vaccines are seeing their first large scale deployment now, but they are based on decades of research. Humans know a lot about mRNA, which is how they even became possible. I prefer the more precise approach mRNA vaccines provide. Mind you, they are both good for our current situation. I would have gladly taken J&J if that was the option. Ended up getting Pfizer due to the current halt and I'm very happy about that. It's just that mRNA vaccines open up entire new treatment options. We have come a long way from having to grow viruses in chicken eggs (which is something that's still done).
- roofwellhams 6y ago
  What if there is something that nobody figure out yet, but we will only figure out if there are many people vaccinated? I think it's a valid question. Just because in theory it should work, doesn't mean in real world will work.
- blabitty 6y ago
  >And if that protein turns out to be harmful long term, guess what, the virus has it too. It's not peer reviewed yet but here is this:https://www.medrxiv.org/content/10.1101/2021.03.05.21252960v1.full https://www.medrxiv.org/content/10.1101/2021.03.05.21252960v... Evidence of the spike protein by itself causing clotting issues.
  - deleted 6y ago
    [deleted]
ars 6y ago
I was also nervous. But I was reassured when I discovered the first Clinical trials were one year ago (almost to the day). Additionally the number of shots we have given (around 200 million, probably more) is effectively the worlds largest clinical trial. If there were problems, even rare ones, we would hear about it by now. Those two things reassured me to the point that I went and got the shot.
- logicchains 6y ago
  > If there were problems, even rare ones, we would hear about it by now. Not if they were long-term effects that took 1-2 years+ to manifest.
  - kolinko 6y ago
    Long-term effects follow a bell curve, so if they took 1-2 years to show up in average, with 200M vaccinated people, we would see initial cases already. Also, there have been no long term effects of a vaccine that didn’t begin in a first month-post vaccination, ever. There is no theory even on how would it be possible for them to manifest after more than a year if nothing happened before.
azinman2 6y ago
They’ve been used for cancer for several years now. They’re not new.
feyman_r 6y ago
>> This is making me want to take the J&J one instead. AFAIK [1], even Viral Vector vaccines haven't been around for a long time either; just the Ebola one apart from CoVID. The majority of vaccines prevalent since a long time have either been inactivated or attenuated vaccines. The only CoVID inactivated vaccines are listed here [2], a couple of them being the ones in China, India and Russia. [1] https://en.wikipedia.org/wiki/Viral_vector_vaccine https://en.wikipedia.org/wiki/Viral_vector_vaccine [2] https://en.wikipedia.org/wiki/COVID-19_vaccine#Inactivated_virus_vaccines https://en.wikipedia.org/wiki/COVID-19_vaccine#Inactivated_v...
- Fomite 6y ago
  And the HPV vaccine before that was a virus-like particle vaccine, which was new tech as well. We've effectively run out of low hanging fruit where inactivated or live-attenuated vaccines are really amenable for use.
bonniemuffin 6y ago
I'm not specifically an mRNA vaccine expert, but I have a biomedical science PhD, and my "generally well educated in this area" gut feeling is that mRNA vaccines are a simple, "clean" formulation with less chances for something surprising to go wrong compared to other vaccine formulations. I got the Moderna shot and I've been totally nerding out about how cool it is. It's just mRNA, which basically falls apart when you look at it funny, with just enough lipids to hold it together until it gets into your cells. If there were going to be terrible side-effects, I would expect them to show up immediately or not at all, since the constituent ingredients are simple things that break down quickly in the body.
- haltingproblem 6y ago
  I got the Moderna as well. The second dose, was quite a ride. Your description of mRNA vaccine, coming from a domain expert is quite soothing.
- symlinkk 6y ago
  Then why haven’t we used them before? I’m not arguing with you btw, just asking a question as I have no knowledge in this area whatsoever.
  - D-Coder 6y ago
    mRNAs against viruses were still in research until the past few years. Researchers were trying to use it against flu until COVID broke out. https://www.theatlantic.com/ideas/archive/2021/03/how-mrna-technology-could-change-world/618431/ https://www.theatlantic.com/ideas/archive/2021/03/how-mrna-t...
    - dhdhhdd 6y ago
      Devil's advocate: why were they not successful in developing one against flu, but we're quickly successful when creating one for covid?
      - sdenton4 6y ago
gottebp 6y ago
Since the hijacked cells expressing the spike protein are your own, presumably they still emit "friendly" signals to the immune system (eg: I am self, do not attack). I am curious how the immune system would even recognize the spike proteins as bad in this case. If the vaccine has some mechanism to attract attention to the spike, is there a risk that antibodies could develop to the cells themselves for instance?
- deleted 6y ago
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- sgtnoodle 6y ago
  As someone with sarcoidosis, that is my worry too. Also, for folk that already developed antibodies against those spike proteins, it seems like shotgunning a bunch of mRNA into their cells might lead to a rather severe inflammatory response, worse than re-exposure to the virus. Anecdotally, I have a very elderly acquaintance that reacted quite poorly to the vaccine, including developing "shingles" in her eye. A nurse taking care of her then accidentally exposed her to COVID, which she subsequently tested positive for but had no symptoms.
  - nerdponx 6y ago
    I wonder if some of the people having fevers and other flu-like side effects are people who were asymptomatic Covid carriers at one point! I don't have a condition nearly as serious as sarcoidosis, but I also worry that I will be one of the unlucky ones with a more serious side effect.
    - Izkata 6y ago
      > I wonder if some of the people having fevers and other flu-like side effects are people who were asymptomatic Covid carriers at one point! I saw a similar claim about a week ago, that the correlation is high between people who were actually sick and then also got side-effects from a vaccine. They didn't include a reference, but if I see it again I'll definitely be poking them for one.
deleted 6y ago
[deleted]
01100011 6y ago
Lots of good responses to assuage your fears. The one thing I don't see a response to is the auto-immune angle. Let's assume that the mRNA vaccine quickly goes away, but the whole point of it is to train your immune system to attack the spike protein. How confident are we that the spike protein isn't naturally occuring in any human cell type in any population of humans on the planet? Can we say with near-certainty that the likelihood of an autoimmune issue is non-existant? I'm not very worried about it. I just received my first dose of the Pfizer vaccine today(some soreness at the injection site and fatigue ~12h after). I just would like to hear the response to that concern in case someone tries to argue that angle with me.
- AareyBaba 6y ago
  Biology is messy and you can not say for certain that there will never be a group of individuals with an autoimmune issue. That is why vaccines go through several clinical trial phases. I recommend listening to this lecture about the process: https://youtu.be/35Idb_lCU4o?t=61 https://youtu.be/35Idb_lCU4o?t=61
- rflrob 6y ago
  We actually know the primary sequence (i.e. order of amino acids) for every gene in the body. It’s trivially easy (a senior undergrad in bioinformatics ought to be able to do it with little or no handholding) to look for genes with even a vaguely similar sequence. Protein folding is a hard problem, but the space of possible solutions is large enough that it’s unlikely that an unrelated sequence would have a similar enough structure to be recognized by the same antibodies. Most variation between populations is not so much what genes are there, but how at what level they are expressed, point mutations, and short repeats (all of which are unlikely to create totally new structures). For there to be a population that had spike protein expressed, there would have to have been some sort of horizontal gene transfer into the germline (which is relatively protected from mutations for precisely this reason) at some point in the past. There’s reasonable atlases of human genetic variation (see, for example, the 1000 genomes project), so if there was some large population of people with any obviously new viral sequence, we’d see it. Plus, if a person somehow, miraculously, had a protein that looked like Spike, their immune system should already be tuned to ignore it. (I have a PhD in biology, but immunology was not something I have much expertise in, so take this with a grain of NaCl).

colinmcd 6y ago

I'm no biologist, but mRNA is ephemeral by design - it's constantly being broken down in the body. The fact that mRNA is converted to proteins by ribosomes is one of the best understood processes in cellular biology, and synthesizing the mRNA for a new protein is not a new idea. Getting actual viral vectors injected into my arm seems much more concerning on the surface (though it's obviously also very safe).

yasp 6y ago
Were that it was so simple. My understanding is the mRNA used in the vaccines was engineered to be more stable (less ephemeral). Not sure what that means in terms of half life, but AFAICT it's a mistake to assume that it will behave similarly to naturally occurring mRNA if this is true.
- pkaye 6y ago
  They put a lipid coating around the mRNA to protect it. But as soon as that coating is removed, it will be quickly be broken down in the body by various enzymes.
  - yasp 6y ago
    How long does the coating take to be removed? Can the mRNA still be (reverse-)transcribed while in the presence of this coating?
    - pkaye 6y ago
      I'm no expert on this but the lipid coating allows it to enter the cell where the coating is removed and the reverse transcription happens. I've read that any of the mRNA that is injected will be gone within 2-3 in the body.
      - primozk 6y ago
        2-3 what?
        pkaye 6y ago
        days
    - kolinko 6y ago
      If it can be reverse transcribed then so can Covid which has the same mRNA as the vaccine and way way more. Plus, covid infects a million times more cells than the mRNA vaccine.
  - lima 6y ago
    But they also modified the mRNA structure to make it more durable (but still on the order of days/weeks).
- roofwellhams 6y ago
  I agree, if you ever did any software you know perfectly that just adding something might have side effects even if it's 99% the same. There is a risk imo.

detaro 6y ago

One major argument is that the mRNA-part is the initial delivery vehicle that does not stay around, so if it being mRNA-vaccine would cause issues we'd very likely know by now. That said, given that the mRNA-vaccines are used for everybody there is little reason why you shouldn't be able to get J&J if you are more comfortable with that.

shock-value 6y ago

You aren't crazy of course, but all indications are they are quite safe. Additionally, a lot of the excitement around mRNA techniques in general is that it is actually a much "lighter touch" than others in various ways -- e.g. not editing genes like CRISPR, using a much simpler delivery method (lipid delivery vehicle vs adenovirus delivery as in the other vaccines), etc.

Symmetry 6y ago

I'm generally more sanguine with mRNA vaccines than other sorts. The problems we've historically had with vaccines have mostly either been with live attenuated viruses that turned out to not be attenuated enough or with adjuvants. With mRNA there's no virus at all and it works via the normal cell viral infection detection pathways so no need for an adjuvant that might accidentally sensitize you to something else.

dnautics 6y ago

> Like all of you I’m not an expert in the field, but from what I’ve skimmed online it seems like mRNA vaccines have never been used widespread in humans before? Moreover there haven't been any long-term studies... There is a very very small chance that something strange happens [0]. > Am I crazy for being nervous about taking an mRNA COVID shot? You're not crazy, but you're probably being unreasonable. The "gut-feeling" likelihood of something strange happening are very very low. [0] one mRNA-specific example, and one "new investigational drug" example: 1. the mRNA could somehow retrotranspose into your DNA, and cause problems. It's not seen in the lab but that doesn't mean it doesn't happen in vivo, it could also depend on what active retrotranspons you have inside of your cells. 2. the antigen could accidentally elicit an antibody response that activates an oncogenic receptor and increase your chances of getting cancer. I think it's important to note that these are plausible mechanisms and are probably untested/untestable at the scales that matter when you're delivering to millions of people. But plausible does not mean significant. Every time you put something in your body, whatever it is, if it's food from the grocery or that new whiskey that hit the market, you're taking on risk. And keep in mind how convoluted a mechanism it takes to get to the point where it's something risky.

fokinsean 6y ago
I recently came across this study which suggests it can retrotranspose into your DNA. From what I understand they weren't attempting to find that intentionally, but found it while looking into why people were testing positive for COVID many months after being infected and not currently infected. I'm not suggesting that the vaccines could do the same, but it's not that big of a leap to wonder if the virus can retranspose, then the vaccine could as well. Also I'm aware it's a preprint and not fully peer-reviewed yet, interesting nonetheless. https://pubmed.ncbi.nlm.nih.gov/33330870/ https://pubmed.ncbi.nlm.nih.gov/33330870/
e_y_ 6y ago
Absent the cell already being cancerous, wouldn't it eventually die off or become targeted by the immune system (I'm not sure if the synthesized spike proteins are free-floating or if the cell becomes some kind of sacrifice for the immune system to kill and dissect)?

seriousquestion 6y ago

You have to weigh the risk reward for your particular situation. Are you more nervous about a new vaccine or Covid? It depends on your age and comorbidities.

outworlder 6y ago
It doesn't depend on age or comorbidities. Covid vaccines - of any type - are orders of magnitude safer than getting infected by a "live" and constantly mutating virus.

bialpio 6y ago

What dispersed all of the fear for me was reading this: https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source... Especially the part about poly-A tail. IIUC, it means that each mRNA "particle" that gets delivered into your body has an upper limit on how many times the protein will get synthesized from it, and the payload only contains info on the spike protein, so there should be no runaway synthesis of something else that would take over my entire body. Standard disclosure: IANADoctor. Also, got my first shot 3 days ago.

roofwellhams 6y ago
But that's just theory... It's not guaranteed to happen in practice, right?
thehappypm 6y ago
This is an excellent article. Thank you for sharing. This whole pandemic I've been waiting for us to "get lucky" and find that the virus has some weakness. Like some simple off-the-shelf medicine is a cure. Or that it spreads through some simple mechanism we can beat easily. Or that it can't handle summer. Or that it would never mutate. Nothing seemed to go our way though. Then the mRNA vaccines came and that was finally our lucky break! Now thanks to this article I can see that the real breakthroughs came years earlier, from basic researchers. Without these breakthroughs -- which I'm sure didn't excite the public or earn anyone a Nobel prize -- we'd have only inferior vaccines out there.

stopping 6y ago

FYI: The J&J vaccine directly injects DNA into the cell nucleus to begin spike protein production. DNA-based vaccines have been tested before (see J&J's Ebola vaccine), and I believe the general consensus is that mRNA is a safer technology due to its inherently short lifetime.

outworlder 6y ago
Indirectly! It uses an adenovirus as the vector to do so.

trashface 6y ago

I got J&J and am currently waiting around to see if I get a blood clot. Hope I recognize the symptoms. I have a lot of weird aches normally so I might miss it. Hopefully can avoid a multiple-thousand dollar trip to the ER just to find out its nothing. Yes I understand the risk is low, but its higher than the one in a million number everyone is throwing around. Potentially much higher as I suspect that cases in men haven't been reported.

marvin 6y ago
Even if you believe Norway's numbers to be close to your average, it's ~1:20,000. So the odds are still quite safe, and it's thankfully cureable if discovered early.
- trashface 6y ago
  I tell myself this every night when my leg is hurting.
  - marvin 6y ago
    Isn't there a telltale sign with miniature bruises/bleedings in the skin? I think the doctors involved in the study made a list. I'm assuming you've looked at it?
    - trashface 6y ago
      You're right I don't have any of that. And leg is feeling better. I'm probably fine and should stop worrying.
- ostenning 6y ago
  What? That number is huge!
  - marvin 6y ago
    Well, now you know why Denmark and Norway suspended AZ vaccinations for everyone, and many European countries stopped them for everyone younger than 65. It wasn’t because their governments are antivaxxers.

marvin 6y ago

I've been thinking the same things, that there is a small likelihood there's a nasty black swan hiding in there somewhere. But in addition to the theory, we're approaching one year of empirical data on large-scale clinical trials, soon improving by the millions every day. So I'm less and less nervous for such a "holy shit, who could have imagined that" moment for each week that passes. That the rare AZ/J&J side effects were promptly discovered is also a good sign that the monitoring system works.

ycombinete 6y ago

I went with Sinopharm, even though I did have the choice to take Pfizer. I prefer the idea of a traditional vaccine. I’ll see how MRNA looks after this mass beta testing is complete.

outworlder 6y ago

> This is making me want to take the J&J one instead. On one hand, we have mRNA, which is self-limiting and that we know exactly what it encodes, as every single base has been put in there by us. We know what protein it encodes. And if that protein turns out to be harmful long term, guess what, the virus has it too. On the other hand, we have a viral vector vaccine, which injects a live adenovirus which then delivers the instructions? I know we have chosen a harmless virus, but it's an entire virus nonetheless. mRNA vaccines are seeing their first large scale deployment now, but they are based on decades of research. Humans know a lot about mRNA, which is how they even became possible. I prefer the more precise approach mRNA vaccines provide. Mind you, they are both good for our current situation. I would have gladly taken J&J if that was the option. Ended up getting Pfizer due to the current halt and I'm very happy about that. It's just that mRNA vaccines open up entire new treatment options. We have come a long way from having to grow viruses in chicken eggs (which is something that's still done).

roofwellhams 6y ago
What if there is something that nobody figure out yet, but we will only figure out if there are many people vaccinated? I think it's a valid question. Just because in theory it should work, doesn't mean in real world will work.
blabitty 6y ago
>And if that protein turns out to be harmful long term, guess what, the virus has it too. It's not peer reviewed yet but here is this:https://www.medrxiv.org/content/10.1101/2021.03.05.21252960v1.full https://www.medrxiv.org/content/10.1101/2021.03.05.21252960v... Evidence of the spike protein by itself causing clotting issues.
- deleted 6y ago
  [deleted]

ars 6y ago

I was also nervous. But I was reassured when I discovered the first Clinical trials were one year ago (almost to the day). Additionally the number of shots we have given (around 200 million, probably more) is effectively the worlds largest clinical trial. If there were problems, even rare ones, we would hear about it by now. Those two things reassured me to the point that I went and got the shot.

logicchains 6y ago
> If there were problems, even rare ones, we would hear about it by now. Not if they were long-term effects that took 1-2 years+ to manifest.
- kolinko 6y ago
  Long-term effects follow a bell curve, so if they took 1-2 years to show up in average, with 200M vaccinated people, we would see initial cases already. Also, there have been no long term effects of a vaccine that didn’t begin in a first month-post vaccination, ever. There is no theory even on how would it be possible for them to manifest after more than a year if nothing happened before.

azinman2 6y ago

They’ve been used for cancer for several years now. They’re not new.

feyman_r 6y ago

>> This is making me want to take the J&J one instead. AFAIK [1], even Viral Vector vaccines haven't been around for a long time either; just the Ebola one apart from CoVID. The majority of vaccines prevalent since a long time have either been inactivated or attenuated vaccines. The only CoVID inactivated vaccines are listed here [2], a couple of them being the ones in China, India and Russia. [1] https://en.wikipedia.org/wiki/Viral_vector_vaccine https://en.wikipedia.org/wiki/Viral_vector_vaccine [2] https://en.wikipedia.org/wiki/COVID-19_vaccine#Inactivated_virus_vaccines https://en.wikipedia.org/wiki/COVID-19_vaccine#Inactivated_v...

Fomite 6y ago
And the HPV vaccine before that was a virus-like particle vaccine, which was new tech as well. We've effectively run out of low hanging fruit where inactivated or live-attenuated vaccines are really amenable for use.

bonniemuffin 6y ago

I'm not specifically an mRNA vaccine expert, but I have a biomedical science PhD, and my "generally well educated in this area" gut feeling is that mRNA vaccines are a simple, "clean" formulation with less chances for something surprising to go wrong compared to other vaccine formulations. I got the Moderna shot and I've been totally nerding out about how cool it is. It's just mRNA, which basically falls apart when you look at it funny, with just enough lipids to hold it together until it gets into your cells. If there were going to be terrible side-effects, I would expect them to show up immediately or not at all, since the constituent ingredients are simple things that break down quickly in the body.

haltingproblem 6y ago
I got the Moderna as well. The second dose, was quite a ride. Your description of mRNA vaccine, coming from a domain expert is quite soothing.
symlinkk 6y ago
Then why haven’t we used them before? I’m not arguing with you btw, just asking a question as I have no knowledge in this area whatsoever.
- D-Coder 6y ago
  mRNAs against viruses were still in research until the past few years. Researchers were trying to use it against flu until COVID broke out. https://www.theatlantic.com/ideas/archive/2021/03/how-mrna-technology-could-change-world/618431/ https://www.theatlantic.com/ideas/archive/2021/03/how-mrna-t...
  - dhdhhdd 6y ago
    Devil's advocate: why were they not successful in developing one against flu, but we're quickly successful when creating one for covid?
    - sdenton4 6y ago

gottebp 6y ago

Since the hijacked cells expressing the spike protein are your own, presumably they still emit "friendly" signals to the immune system (eg: I am self, do not attack). I am curious how the immune system would even recognize the spike proteins as bad in this case. If the vaccine has some mechanism to attract attention to the spike, is there a risk that antibodies could develop to the cells themselves for instance?

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sgtnoodle 6y ago
As someone with sarcoidosis, that is my worry too. Also, for folk that already developed antibodies against those spike proteins, it seems like shotgunning a bunch of mRNA into their cells might lead to a rather severe inflammatory response, worse than re-exposure to the virus. Anecdotally, I have a very elderly acquaintance that reacted quite poorly to the vaccine, including developing "shingles" in her eye. A nurse taking care of her then accidentally exposed her to COVID, which she subsequently tested positive for but had no symptoms.
- nerdponx 6y ago
  I wonder if some of the people having fevers and other flu-like side effects are people who were asymptomatic Covid carriers at one point! I don't have a condition nearly as serious as sarcoidosis, but I also worry that I will be one of the unlucky ones with a more serious side effect.
  - Izkata 6y ago
    > I wonder if some of the people having fevers and other flu-like side effects are people who were asymptomatic Covid carriers at one point! I saw a similar claim about a week ago, that the correlation is high between people who were actually sick and then also got side-effects from a vaccine. They didn't include a reference, but if I see it again I'll definitely be poking them for one.

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01100011 6y ago

Lots of good responses to assuage your fears. The one thing I don't see a response to is the auto-immune angle. Let's assume that the mRNA vaccine quickly goes away, but the whole point of it is to train your immune system to attack the spike protein. How confident are we that the spike protein isn't naturally occuring in any human cell type in any population of humans on the planet? Can we say with near-certainty that the likelihood of an autoimmune issue is non-existant? I'm not very worried about it. I just received my first dose of the Pfizer vaccine today(some soreness at the injection site and fatigue ~12h after). I just would like to hear the response to that concern in case someone tries to argue that angle with me.

AareyBaba 6y ago
Biology is messy and you can not say for certain that there will never be a group of individuals with an autoimmune issue. That is why vaccines go through several clinical trial phases. I recommend listening to this lecture about the process: https://youtu.be/35Idb_lCU4o?t=61 https://youtu.be/35Idb_lCU4o?t=61
rflrob 6y ago
We actually know the primary sequence (i.e. order of amino acids) for every gene in the body. It’s trivially easy (a senior undergrad in bioinformatics ought to be able to do it with little or no handholding) to look for genes with even a vaguely similar sequence. Protein folding is a hard problem, but the space of possible solutions is large enough that it’s unlikely that an unrelated sequence would have a similar enough structure to be recognized by the same antibodies. Most variation between populations is not so much what genes are there, but how at what level they are expressed, point mutations, and short repeats (all of which are unlikely to create totally new structures). For there to be a population that had spike protein expressed, there would have to have been some sort of horizontal gene transfer into the germline (which is relatively protected from mutations for precisely this reason) at some point in the past. There’s reasonable atlases of human genetic variation (see, for example, the 1000 genomes project), so if there was some large population of people with any obviously new viral sequence, we’d see it. Plus, if a person somehow, miraculously, had a protein that looked like Spike, their immune system should already be tuned to ignore it. (I have a PhD in biology, but immunology was not something I have much expertise in, so take this with a grain of NaCl).