I did a lot of research on this last year. Here are the best answers I could find out to your questions:
1. This is possible. No real information is public on how dose ranging was done. The closest I could get is the suggestion that doses were calculated based on animal experiments by simply starting high and reducing it until the animals didn't seem to get sick or die anymore. So, doses appear to be the highest tolerable in whatever sample size they used to do this. If there's deeper theory behind the doses it's unclear what it can be because Moderna dosage is 3x stronger than Pfizer for no obvious reason (they are advertised as granting equivalent protection).
2. Yes, vaccinating against CoVs is ~useless and can backfire. There was evidence in the research literature about this before COVID. There are two related problems:
2a. Useless: respiratory viruses like CoVs and influenza can mutate very fast. Nobody ever made a vaccine against the common cold because the viruses mutate beyond it immediately, rendering the vaccine useless. Flu vaccines routinely have efficacy of <20% or even zero because they get made for a variant that doesn't then emerge. It was not a huge leap to realize that the fast mutation problem was also going to apply here, and indeed just months after vaccination started Omicron appeared and replaced Delta completely.
2b. Can backfire: There can be a problem called OAS or antigenic fixation. The immune system appears to lack fine grained resolution. After the immune system memorizes a virus it's possible for it to get confused and think it's detected that virus when in reality it's seeing a slight mutation. When this happens it produces antibodies to the older antigens, and if the virus mutated in such a way that they're now less effective this can lead to the virus not being stopped properly. In other words it can make things worse. Not all viruses are as unstable as CoVs so this problem doesn't occur with e.g. smallpox, but SARS-CoV-2 is very unstable. There's some evidence that COVID vaccines can cause this effect unfortunately, whereby the immune system produces antibodies to the long extinct Wuhan 2019 strain instead of the one the body was actually exposed to.
3. mRNA tech is very neat in theory but there are two major possible issues:
3a. It never launched before COVID because it was plagued with extremely severe toxicity problems that caused any drug using it to fail trials / safety approvals. The problem seemed to be the lipid nanoparticle wrapper which became toxic on repeat doses. Most drugs require repeat doses so that's a problem. Moderna was a failing biotech firm before COVID because of this. They couldn't find a solution so pivoted to vaccines. Why? Because - pre COVID - vaccines were assumed to be something you take once and then you're done for many years or for life, so it was a way to dodge the repeat-dose-toxicity problem rather than solve it. Well, then COVID mass hysteria infected the globe and people are being forced to take 2, 3, 4 doses. So we're well into repeat doses territory. How many doses did Moderna's tech become toxic after, exactly? That's not public AFAIK.
3b. We were assured that the mRNA disappears from the body within a few days. That turned out to be false and mRNA spike can be found collecting in different parts of the body weeks or even months after injection. Because research that could undermine vaccines is so rare and hard to get published, and because mRNA vaccines are so new, why this happens is unclear. However some doctors have speculated that it's to do with the pseudo-uridine substitutions they do. (mRNA vaccines disable the immune system's normal defenses against foreign mRNA using some chemical tricks).
On the other hand, mRNA itself is probably not the cause of the heart/clotting problems. AstraZeneca's vaccine doesn't use mRNA and has the same issues. The problem is more likely that the spike protein is toxic and can cause these problems if it gets into the bloodstream. Doesn't matter how you make it.
Thank you for your reply. People who disagree with you should be less lazy and give their own answers, or rebut yours. I take your commen as a reasonable lay person's conclusion based on their best effort (given whatever constraints).
2--exactly the same thing happens if you get the disease. Thus it's not a reason against the vaccine unless the probably of it mutating before you catch it is high.
You mean OAS? That can happen yes and is theorised to be why flu gets deadlier as people get older, their immune system gets more and more confused by memories of flus from people's youth.
In this case, the problem is that it accelerates the spread. Normally in any epidemic there's a large population of people who were never infected, so it's their first time and the body becomes highly immune. They act as buffers that stop the virus from spreading so fast to those unlucky enough to have got the earlier version. You end up with a diverse population of people immune to different variants which slows them all down.
If you fix everyone on a variant that hasn't existed for years then this buffering effect is eliminated. Everyone becomes equally vulnerable to reinfection. This is posited as the explanation for why do many vaccinated people seem to be susceptible to rapid reinfection. Although it can be happen naturally too, the wider social diversity that would make that happen say every few years is gone, so now it can happen every few months instead.
1. This is possible. No real information is public on how dose ranging was done. The closest I could get is the suggestion that doses were calculated based on animal experiments by simply starting high and reducing it until the animals didn't seem to get sick or die anymore. So, doses appear to be the highest tolerable in whatever sample size they used to do this. If there's deeper theory behind the doses it's unclear what it can be because Moderna dosage is 3x stronger than Pfizer for no obvious reason (they are advertised as granting equivalent protection).
2. Yes, vaccinating against CoVs is ~useless and can backfire. There was evidence in the research literature about this before COVID. There are two related problems:
2a. Useless: respiratory viruses like CoVs and influenza can mutate very fast. Nobody ever made a vaccine against the common cold because the viruses mutate beyond it immediately, rendering the vaccine useless. Flu vaccines routinely have efficacy of <20% or even zero because they get made for a variant that doesn't then emerge. It was not a huge leap to realize that the fast mutation problem was also going to apply here, and indeed just months after vaccination started Omicron appeared and replaced Delta completely.
2b. Can backfire: There can be a problem called OAS or antigenic fixation. The immune system appears to lack fine grained resolution. After the immune system memorizes a virus it's possible for it to get confused and think it's detected that virus when in reality it's seeing a slight mutation. When this happens it produces antibodies to the older antigens, and if the virus mutated in such a way that they're now less effective this can lead to the virus not being stopped properly. In other words it can make things worse. Not all viruses are as unstable as CoVs so this problem doesn't occur with e.g. smallpox, but SARS-CoV-2 is very unstable. There's some evidence that COVID vaccines can cause this effect unfortunately, whereby the immune system produces antibodies to the long extinct Wuhan 2019 strain instead of the one the body was actually exposed to.
3. mRNA tech is very neat in theory but there are two major possible issues:
3a. It never launched before COVID because it was plagued with extremely severe toxicity problems that caused any drug using it to fail trials / safety approvals. The problem seemed to be the lipid nanoparticle wrapper which became toxic on repeat doses. Most drugs require repeat doses so that's a problem. Moderna was a failing biotech firm before COVID because of this. They couldn't find a solution so pivoted to vaccines. Why? Because - pre COVID - vaccines were assumed to be something you take once and then you're done for many years or for life, so it was a way to dodge the repeat-dose-toxicity problem rather than solve it. Well, then COVID mass hysteria infected the globe and people are being forced to take 2, 3, 4 doses. So we're well into repeat doses territory. How many doses did Moderna's tech become toxic after, exactly? That's not public AFAIK.
https://www.statnews.com/2017/01/10/moderna-trouble-mrna/
3b. We were assured that the mRNA disappears from the body within a few days. That turned out to be false and mRNA spike can be found collecting in different parts of the body weeks or even months after injection. Because research that could undermine vaccines is so rare and hard to get published, and because mRNA vaccines are so new, why this happens is unclear. However some doctors have speculated that it's to do with the pseudo-uridine substitutions they do. (mRNA vaccines disable the immune system's normal defenses against foreign mRNA using some chemical tricks).
On the other hand, mRNA itself is probably not the cause of the heart/clotting problems. AstraZeneca's vaccine doesn't use mRNA and has the same issues. The problem is more likely that the spike protein is toxic and can cause these problems if it gets into the bloodstream. Doesn't matter how you make it.