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No one who got Moderna's vaccine in trial developed severe Covid-19

sciencemag.org

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Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#201

Post by inglor_cz »

IgorPartola wrote: post #73
newdude116 wrote: post #49

Thats good but I would not be overly optimistic. Two question since I dont know much about mRNA vaccines 1. The mRNA has to express the target Protein for the Anitbodies. If injected, how does this happen? It has to go somehow into the cell to be translated? Or is the delivery vehicle the magic sauce? 2. What makes mRNA vaccines so special? What is the difference of injecting the expressed protein sequence directly?

I have no knowledge of this but if injecting spike proteins worked wouldn’t we just always do that? Seems like way easier than the rest of the delivery mechanism.

Whenever you inject foreign biological material, you have to avoid two scenarios:

a) the scenario when the foreign material is immediately degraded by enzymes or other mechanism, before actually accomplishing anything,

b) the scenario when the foreign material causes massive immune reaction in form of inflammation, potentially killing the host.

AFAIK navigating between those two extremes took decades during development of RNA vaccines. But now it seems that we can avoid both.

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#202

Post by cm2187 »

tpmx wrote: post #83
mrjaeger wrote: post #22

Earlier quoted context omitted.

Can read all of them in their published protocol at https://www.modernatx.com/sites/default/files/mRNA-1273-P301... under section 5.2.

Relevant criteria for the question "does it it exclude old, fragile people with various common pre-existing conditions?" (not exhaustive, but indicative): Included: Pre-existing conditions are okay as long as they are in a stable condition (defined as no significant change in therapy etc for the 3 months before enrollment). Excluded: Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections (H…

That could exclude people who are the most likely of dying of covid (a severe case of covid doesn't mean dying, for instance I heard an ICU specialist explaining that people who are seriously obese often require ICU treatment but rarely die from it, the people who die usually have serious co-morbidities and an already reduced life expectancy).

But it's kind of secondary anyway. The main goal of the vaccine is to stop the virus from spreading in the population and getting a chance to reach vulnerable people. Even if it were to only protect people who wouldn't die of Covid in the first place, that's the vast majority of the population and enough to significantly reduce the chance of spreading.

At the condition that these studies measure the right thing. If it merely stops the symptoms but doesn't stop the spread of the virus, that may be a problem.

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#203

Post by chimeracoder »

tsimionescu wrote: post #196
disgruntledphd2 wrote: post #177

Earlier quoted context omitted.

Yeah, agreed. My selfish concern is then whether or not the vaccine will work for them.

Unfortunately, vaccines can't really help immunocompromised people, as their immune system is simply unable to fight off any infection, regardless of whether it recognizes the infection or not (of course, this may be a matter of degrees). That is why, for example, people with advanced AIDS can die from essentially any pathogen.

Your answer isn't exactly wrong, but it's painting with a broad brush. "immunocompromised" is a broad term (even more so than "immunosuppressed"), so there definitely are people who are immunocompromised who could potentially benefit from a vaccine (again, we don't have hard data on that yet for any of the vaccine candidates and won't for a while).

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#204

Post by tsimionescu »

dotuser wrote: post #188
Majromax wrote: post #125

Earlier quoted context omitted.

Immune suppressed/deficient patients are not good candidates for vaccines in the first place, since they would be unlikely to mount an effective immune response.

That sounds backwards. Shouldn't those with weakened immune response be first in line for the vaccine? The vaccine would give them a boost. Those with strong immune response have a better chance of fighting off the virus.

Vaccines work by essentially teaching your immune system to recognize a pathogen. If your immune system is in a very weakened state, it likely will not 'learn', and even if it does, it may not be in any condition to fight the infection, even if it recognizes it as such. Of course, things are much more complicated, but in people with severe immuno-deficiency (such as advanced AIDS or people who are actively taking immune suppressants) a vaccine will not have any effect (some kinds of vaccines even risk infecting that person with the disease, though I beleiev this is not the case with any of the Covid19 vaccines).

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#205

Post by inglor_cz »

ed25519FUUU wrote: post #58
blhack wrote: post #48

Does anybody have a good link for a layman's overview of how mRNA vaccines work? Lot's of nervousness from people around this, and would love to be able to help quell some of that.

Edit: I do plan to get the vaccine, but as a software engineer I know beta versions usually have the most “bugs” — and I have the health privilege to be in the back of the line so I will!

This method has been in development since 1978 (when then-young Hungarian scientist Katalin Karikó started playing with mRNA in her lab in Szolnok) until today. Hundreds of mice died during the search for bugs before anyone dared to inject a human subject.

It cannot be ruled out that the whole concept of RNA vaccines still has bugs, but it is nowhere near "it compiles, ship it now!" software betas. The process is much more risk-averse.

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#206

Post by bsmith89 »

orblivion wrote: post #195
Balgair wrote: post #182

Earlier quoted context omitted.

Ahh, yes, ModeRNA's vaccine is some very clever stuff. The way that one works is a bit complex. Essentially, they still want your immune system to recognize that the virus is bad and then make antibodies against it. Usually, you inject broken up bits of a dead virus into a person. The immune system sees the foreign objects, and makes antibodies against it. Withe ModeRNA's vaccine, we go inside out. You have the body…

I'm wondering if you could clarify a couple things for me: 1) "Skipping steps" This appears to be doing the opposite. In an old vaccine, you'd just dump a bunch of spike proteins into the system. Here, you're adding the step of making the body produce them. Could you clarify? 2) Why not just produce those spikes in a lab? Is it just much less resource intensive to have the bodies make them? 3) As far as stressing tha…

1) Yeah, besides picking the step of manufacturing virus parts, I agree, this is going a step back in the virus's life cycle.

2) It's hard to produce proteins in the lab. Our own cells are pro at it, though, including all of the post-translational modifications (like attaching sugars and careful protein folding) that can make all the difference.

3) Pretty much. Since it's just one gene being introduced, it will not produce new virions, only the spike protein that our immune system needs to recognize.

Source: Am microbiologists, although not a virologist.

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#207

Post by ogre_codes »

ed25519FUUU wrote: post #58
blhack wrote: post #48

Does anybody have a good link for a layman's overview of how mRNA vaccines work? Lot's of nervousness from people around this, and would love to be able to help quell some of that.

Edit: I do plan to get the vaccine, but as a software engineer I know beta versions usually have the most “bugs” — and I have the health privilege to be in the back of the line so I will!

The beta test (clinical trials) are long over, they had it months ago.

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#208

Post by tsimionescu »

CamperBob2 wrote: post #189
orblivion wrote: post #134

Earlier quoted context omitted.

I'm an atheist more or less and I agree with this sentiment. I'm not fond of transhumanism. But I don't think the mRNA vaccine process fits this description.

Quite a bit of our DNA isn't "human" to begin with, never mind our cells themselves. In fact, most of the cells in our bodies are bacterial, as I understand it. (Edit, that's oversimplified and/or inaccurate, see below.)

That's highly debatable. Also, obviously 'most' begs the question 'most by what?' if it's just by number, then that seems unlikely but possible. But most by weight, volume, or, more importantly, functionality - not really, that's definitely human cells.

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#209

Post by ponker »

hobs wrote: post #42
ed25519FUUU wrote: post #32

Earlier quoted context omitted.

If it cures late stage cancer a few million per treatment would actually be a bargain. Edit: I have no clue why people would rather something not exist than for something to exist but for it to be too expensive.

Considering that no, we dont have a few million per person than no, its not really a "bargain" unless you mean in the context of a pact with the devil.

Well it depends why it costs a few million per person. If the production of the vaccine takes thousands of tons of coal and hundreds of pounds of bark of a slow-growing tree then yes, we don't have that per person. But if the current million dollar price is to enrich some pharma investors then there's nothing to say that society needs to find $100 trillion to enrich someone.

Re: No one who got Moderna's vaccine in trial developed severe Covid-19

#210

Post by tsimionescu »

mantap wrote: post #163
hobs wrote: post #42

Earlier quoted context omitted.

Considering that no, we dont have a few million per person than no, its not really a "bargain" unless you mean in the context of a pact with the devil.

You can't just multiply the cost for 1 person by the number of people in the population. If it's mass produced it will be a lot cheaper. e.g. if you want to pay a chemist to synthesise Aspirin in a lab for you it will be very expensive. But it costs pennies in the store.

That's only true if you can use the same aspirin as many other people. If the specific substance needs to be adjusted to your specific tumor, it may remain extremely expensive for a long time - until it becomes a technician's job to find your specific cancer signature and synthesize the drug from it.
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