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We stan moderna (i.redd.it)

submitted by rpolly18

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[–][deleted] 97 points98 points  (2 children)

This meme reminds me of something my first professor within my major said. Her thesis project was actually competing with research from another university that was coming to their own unique conclusions about the problem that was being investigated. Her PhD adviser had her submit portions of her thesis to a journal in order to establish their ideas first. By doing so, they essentially forced the competing universities' research out of the discussion, and my professor and the university were inevitably awarded grants that they had been mutually applying for. To further salt the wound, she said she actually cited a few of the competing researchers papers for her final thesis as well.

Science can be super cutthroat yo.

[–]thumbsquare 8 points9 points  (1 child)

Is it typical for thesis research to be published on its own in chemistry/geology? For biomedical sciences in the US, it’s expected that we publish as we do our PhD, and our thesis more-or-less becomes a compilation of those papers with filler tying the papers together.

[–][deleted] 0 points1 point  (0 children)

It's atypical for sure, but it could happen. She said they did it solely to get ahead of the other university and secure more funding.

[–]bleak_gypsum 143 points144 points  (11 children)

Seriously doubt that the difference in efficacy is statistically significant.

[–]pastaandpizza 82 points83 points  (0 children)

Narrator: It's not.

[–]rpolly18[S] 55 points56 points  (1 child)

I also doubt it’s significant. Pfizer also published “>90%” or something like that. Both are way higher than expected/necessary to alleviate the pandemic though so

[–]bleak_gypsum 7 points8 points  (0 children)

Yes great news regardless

[–]Salty_Grundle 6 points7 points  (0 children)

9/94 vs 5/95 for Pfizer vs moderna. Yeah not any real difference

[–]lameduckfolio 4 points5 points  (6 children)

with a sample size of 90-some if I heard right

[–][deleted] 33 points34 points  (2 children)

95ish total cases. Not 95 participants.... End point is 150ish. So they're about 2/3 through the study in terms of cases. Should wrap up soon though with spike in covid accelerating the study temporally

[–]lameduckfolio 1 point2 points  (1 child)

ah, well thats better news.

[–]resorcinarene 11 points12 points  (0 children)

The spike is good news? Dark, but I like it

[–]ColaRBT16 3 points4 points  (0 children)

Pfizer trial was 44,000 participants.

[–]Clonazep4m -1 points0 points  (0 children)

He meant between the two vaccines

[–]letsgetmolecular 90 points91 points  (20 children)

*Same efficacy

[–]shieldvexor 87 points88 points  (19 children)

You'd think people here would understand confidence intervals.

[–]1337HxCCancer Bio/Comp Bio 109 points110 points  (18 children)

Have you seen the discussions on statistics here?

I love this sub, but hub for math it is not.

[–]DankNastyAssMasterMS in Bioanalytical Chemistry 34 points35 points  (4 children)

Didn't somebody just post a published paper a few weeks ago about how terrible biologists are at math?

(PS: Crash Course Statistics on YouTube is a lifesaver.)

[–]FutskiM.Sc. Molecular Biology 9 points10 points  (3 children)

Best illustrated in the case of Dr. Mary M Tai, who in 1994 came up with, and took credit for discovering a mathematical model, that allow you to determine the area under a curve. This article currently has 405 citations, of which I hope a few of them are just people who did it for fun.

[–]PM_ME_YOUR_LUKEWARM 0 points1 point  (2 children)

I'm confused, are you saying it is wrong?

And isn't integral just area under curve?

[–]FutskiM.Sc. Molecular Biology 1 point2 points  (1 child)

No no, it's not that it's wrong...

It's just that it has been proven mathematical knowledge for over 300 years, but these people present it as a novel discovery, something they would have known if they had paid attention in calculus classes.

[–]PM_ME_YOUR_LUKEWARM 0 points1 point  (0 children)

ahhh, gotcha, whooshed right over my head.

thank you, didn't know what a metabolic curve was

[–]chahudChemistry gang 46 points47 points  (10 children)

To be fair, statistics is the devils math...created to deceive people. And be confusing and counterintuitive as fuck

[–]1337HxCCancer Bio/Comp Bio 24 points25 points  (4 children)

Honestly, I don't think it's so bad - at least in the majority of applications you see in bench science. The issue is you run into people (more often than not, unfortunately) who "have always done it this way" or "were taught to do it this way" and simply will not change their method. Think of something like qPCR Excel sheets - how many variations of those have you seen?

This makes statistics seems scary and weird because it feels very inconsistent, and it just shouldn't happen. While there are some nuances in statistics that can be a bit less "absolute" than others, 99% of what you actually need for a molecular biology lab has strictly correct/incorrect approaches (e.g. no, you can't just use SEM for error because "it makes the bars smaller").

Unfortunately, most of academia doesn't seem to actually care, and you see weird/bad stats published all the time. I've seen log-scale error bars on relative expression qPCR, qPCR without statistics at all, SEM error bars for no reason, t-tests without proper correction for multiple testing, etc.

[–][deleted] 16 points17 points  (1 child)

Academia also has an obsession with p<0.05.... not saying that 0.05 is a bad cut off but there is nothing magical that happens at this threshold.

Not to mention that this tells you anything about the significance of the difference, just that it is statistically significant.

[–]1337HxCCancer Bio/Comp Bio 15 points16 points  (0 children)

Sure. But this issue is once you've bought into the frequentist model... you're a bit stuck with 0.05. You can, of course, report any p value you like, but obviously some people will throw a fit with p = 0.06 or whatever.

Not to mention that this tells you anything about the significance of the difference, just that it is statistically significant.

This is also pretty often overlooked. There's a big difference between statistically significant and biologically significant. I'm fairly certain lots of what we as a field study fits the former category much more frequently than the latter.

[–]TheMiiChannelTheme 0 points1 point  (1 child)

Think of something like qPCR Excel sheets

Or just Excel in general.

[–]1337HxCCancer Bio/Comp Bio 0 points1 point  (0 children)

I have entire rants about excel but I figured this wasn't the place haha

[–][deleted] 0 points1 point  (4 children)

Try bayesian statistics, it makes much more sense for people who are math and logic affine.

The problem with frequentist statistics is that some parts are actually so counterintuitive that they are used wrongly by basically everyone. For example confidence intervals and p-values. Also, statisticians often use assumptions which do not hold, or only hold in the limit of infinite samples. Which means the conclusions are often invalid. Much better than nothing, though.

[–]Marethyu999 0 points1 point  (3 children)

How do I know if I've been using frequentist or Bayesian statistics?

[–][deleted] 4 points5 points  (1 child)

If you ask, you have probably used frequentist statistics, but interpreted confidence intervals in the way a Bayesian interprets his credible intervals.

I can recommend the following Material:

Introductory book: Kruschke "Doing Bayesian Data Analysis" .

Also, highly recommended if you want to get real: These practical courses

https://github.com/CamDavidsonPilon/Probabilistic-Programming-and-Bayesian-Methods-for-Hackers

https://github.com/fonnesbeck/Bios8366

[–]Marethyu999 0 points1 point  (0 children)

Probably yeah, i'll look those ressources up, thanks !

[–]Z3ratoss 0 points1 point  (0 children)

Does a prior probability mean anything to you?

[–]FlannelBeardImmunology/Cancer Biology 3 points4 points  (0 children)

Science PhDs by and large don't understand statistics. I had one PI who's only statistics he'd run was t tests between groups, now matter the experiment. It works but life can be easier.

[–][deleted] 0 points1 point  (0 children)

I read that second sentence in a Yoda voice. Thank you

[–]flashmeterred 41 points42 points  (1 child)

It's called a "first to market" vs "best in market" approach. Drug companies are used to it, and will do both approaches. They're fine.

[–]Salty_Grundle 4 points5 points  (0 children)

They both are taking first to market approaches by using a newer but less tested tech. AZ is taking the tried and true approach

[–]AzureRathalos97 17 points18 points  (3 children)

To be fair the Pfizer vaccine was tested on 13 thousand more people than Moderna's candidate so that ~5% difference might not be all that it seems. Either way good positive news for some testing and hopefully we can get more information during review.

[–]Xenarat 2 points3 points  (2 children)

That's true but they're both currently reporting potential efficacy based on their phase 1 numbers which were no where near that large.

[–]AzureRathalos97 0 points1 point  (1 child)

Are you sure? From what I saw in various major outlets is that these were the interim phase 3 results. It was ~43K participants for Pfizer and ~30K for Moderna.

[–]Xenarat 3 points4 points  (0 children)

I went back and re-read to be sure. Mainly, I'm being unclear.

Both studies did enroll a huge number of participants (30k for Moderna) in their phase 3 trials, BUT that means only half of that number was vaccinated (15k). Additionally, these interim reports are only based on the number of people who caught SARS-CoV-2 (95 cases). Basically, it's great news for the vaccinated people but it's still incomplete.

From the infectious rates of 1% we would expect 150 out of the unvaccinated group to be infected. But at this point the infection rates are higher in a lot of places across the US, so I'm expecting a more robust comparison once the final data comes in

[–]Plantpong 26 points27 points  (1 child)

I saw it in the news today. Didn't mention anything too different from the Pfizer one but I feel like they could have mentioned that this one is likely better.

[–]Thunderplant 12 points13 points  (0 children)

The stability is a pretty big difference. They’re saying it only needs to be stored at -20 C /-4F instead of -70 /-94 F which would make a huge difference in the logistics of distributing this thing. They’re also claiming longer stability at fridge and room temperature.

Of course it’s possible this isn’t a real difference and just what has been tested so far, but given they have different formulations it is possible that the stability difference is real.

[–]IamDDT 14 points15 points  (8 children)

What did Moderna do to increase stability? Is it known? 2' modifications? RNase inhibitors? With zero knowledge, I would bet on 2'ome or 2'moes, but I don't know.

[–]letsgetmolecular 28 points29 points  (2 children)

What I've read is that Pfizer simply didn't test the vaccine after -20 C storage. Maybe it is less stable and that's why they didn't, but it's possible they just rushed ahead with their - 70 C stored sample and are therefore only allowed to say it works when stored that way. It's possible they aren't actually super different in that regard.

[–]thisdude415 12 points13 points  (0 children)

They’re probably working on stability in the background and will release that data to FDA.

If they show the drug doesn’t degrade based on storage conditions (I’m HIGHLY suspicious that it can’t tolerate a few weeks at -20), they’ll submit that data any time before January and have the data in time for approval

[–]magnus_max 7 points8 points  (4 children)

For the mRNA part I suspect n1 methyl psudoruridine instead, which they have published in conjunction with Nahum Sonenberg's Lab at McGill University. For the lipid nanoparticle, who knows... I'm not a chemist.

[–]CollateralKite 2 points3 points  (2 children)

Moderna has said they're using modified nucleotides but hasn't specified which one(s). N1M-PseudoUTP might minimize the self attack and degredation but I haven't seen proof of that yet.

The LNP is more the secret sauce of both of these companies and there's hardly any information about what formulations are being used. Even small changes in formulation can greatly change cell transfection and nucleotide release.

[–]spheresquirrel 2 points3 points  (0 children)

Honestly I believe it's LNP. I work with some LNPs and sometimes we even store them at 4C (of course not for long term, but for about a month it's fine)

[–]-Metacelsus- 0 points1 point  (0 children)

there's hardly any information about what formulations are being used.

Don't they have to release the information to get FDA approval? I don't think people would be very keen on injecting an unknown compound.

[–]IamDDT 0 points1 point  (0 children)

Yea... That does make some sense, but does pseudo-u protect against degradation? I would expect some sugar modifications as well as base substitutions.

[–]RedditBResearchPhD Candidate- Cell & Cancer Biology 34 points35 points  (35 children)

Anyone else a little nervous about transfecting our own cells?

[–][deleted] 55 points56 points  (0 children)

Better than letting them get transduced.

[–]DankNastyAssMasterMS in Bioanalytical Chemistry 52 points53 points  (0 children)

Speaking as an analytical chemist who did my grad thesis in a biochem lab, I'm fully planning on getting it and then putting "performed successful transfection" on my resume.

[–]WulfLOLM.Sc | Molecular Biology 12 points13 points  (17 children)

I'm not nervous, but confused.

  • We give the mRNA to some of our cells.
  • These cells start producing the protein.

Wise move, but how does the body distinguish between this and viruses? Won't it make our white cells attack those human cells expressing that protein and kill them on sight, storing some of their epitopes for future uses?

If that's the case, it's an elegant solution, but I feel like I'm missing critical information.

[–]FlyingApple31 26 points27 points  (0 children)

Our immune system has to deal with distinguishing self-epitopes from viral-epitopes with every viral infection we ever get; I don't remember all the details, but the feedback mechanisms are pretty effective (and checking for this is part of the clinical trial)

[–][deleted] 14 points15 points  (15 children)

Roughly speaking: Negative selection and positive selection of antibodies. They present self antigen, if it triggers a response that cell line/antibody is killed off. They present viral antigen, if that produces a response that cell line/Antibody is amplified.

[–]thecorndogmakersequencing research associate 4 points5 points  (12 children)

Thanks, I was confused about why the spike protein expressed from the mRNA wasn't recognized as self by the immune system.

So the reason the spike protein isn't considered "self" is because (at some point during development?) all immune cells with antibodies/receptors with affinity to self proteins were purged?

Does the spike protein need to be associated with any MHC proteins to initiate an immune response?

[–]RedditBResearchPhD Candidate- Cell & Cancer Biology 8 points9 points  (3 children)

Yes. The idea is the mRNA will be translated into only the spike protein, where it will immediately be tagged for degradation and MHC loading to elicit an adaptive response. I’m not so worried about the immune part, as I believe the cells killed by cd8s will have a fine turnover, as much as I am about the genetics. Can’t the mRNA, in theory, be reverse transcribed, then the DNA be potentially translocated into the genome? Also RNA has been found to have deep regulatory functions both intra and extracellularly in recent years. Sure usually these RNAs are processed within the cell differently, but I believe it’s still cause for concern. Maybe someone more knowledgeable in RNA biology can ease my concerns?

[–]CollateralKite 3 points4 points  (0 children)

There are a lot of things that have to both be present and happen in a specific sequence to initiate reverse transcription. In the case of the vaccine mRNAs, they should have been engineered in a way that they avoid the start sites for that process and are thus very safe to use.

[–][deleted] 2 points3 points  (1 child)

Can’t the mRNA, in theory, be reverse transcribed, then the DNA be potentially translocated into the genome?

Isn't the only RT-activity in human cells pretty much just telomerase? I don't see how this would happen at all.

[–]RedditBResearchPhD Candidate- Cell & Cancer Biology 2 points3 points  (0 children)

No, there are quite a lot actually. This is one example.

https://www.jbc.org/content/early/2019/03/06/jbc.RA119.007925.full.pdf

[–][deleted] 2 points3 points  (7 children)

MHC association is required for T cell response. Not necessarily for B cell response, although it might help.

[–]thecorndogmakersequencing research associate 1 point2 points  (6 children)

How does the cell "know" to associate viral proteins with MHC but not self proteins from self mRNA?

[–][deleted] 3 points4 points  (5 children)

MHC does present self proteins. There are several signaling systems to prevent this from causing problems.

[–][deleted] 1 point2 points  (4 children)

I'm kinda clueless when it comes to immunology, but I would really appreciate if you could help me understand this. So I get how the mRNA is translated into a transmembrane protein in our cells. But won't our immune systems attack our own cells if they present the viral antigen?

[–][deleted] 3 points4 points  (3 children)

But won't our immune systems attack our own cells if they present the viral antigen?

That's part of the immune response though: attacking infected cells. That's a feature, not a bug (these things are complicated and immunopathology is a thing, but generally speaking this is true).

[–][deleted] 1 point2 points  (2 children)

Oh I see! I'm guessing there's a fine balance of dosage so you get enough of an immune response to "remember" but low enough so you don't kill too many cells. How would self-amplifying mRNA vaccines control themselves then? Do you know if Moderna or Pzifer are using SAM's?

[–]WulfLOLM.Sc | Molecular Biology 0 points1 point  (1 child)

so to make sure i understand, the human will present that viral protein on its surface and it will be used as an epitope by our memory cells?

[–]CollateralKite 0 points1 point  (0 children)

Correct!

[–]PlasmidDNA 3 points4 points  (2 children)

Both mRNA and DNA have been in years of clinical trials with no health issues stemming from transfection.

[–]pastaandpizza 3 points4 points  (3 children)

I was until these trials made it through without significant vaccine related health events.

[–]RedditBResearchPhD Candidate- Cell & Cancer Biology 0 points1 point  (2 children)

Because this was an expedited trial, I am nervous about the longer term effects. Apparently the efficacy of the RNA versions is much better, but I’m willing to get multiple boosters of the inactivate or attenuated versions of the vaccine to avoid this one.

[–]pastaandpizza 2 points3 points  (1 child)

How many years post-trial are health concerns tracked for normal vs expedited trials before approval? My impression was there was not a difference in safety data collection.

[–]RedditBResearchPhD Candidate- Cell & Cancer Biology 1 point2 points  (0 children)

While I’m not sure if post-trial data is recorded, normal vaccine trials are longer than 6-8 months long, so this allows for more long term data to be acquired. For comparison, the H1N1 vaccine development time was similar to our timeline now for this completely novel virus. This may seem comparable, but developing updated strain vaccines is very different than developing one for a novel virus.

[–]CaptainTurdfinger 2 points3 points  (1 child)

I was hoping I wasn't the only one with reservations. There have been no other FDA approved mRNA vaccines to this point.

I don't feel like now is the time to start giving them to the public willy nilly, there should be a lot more long-term clinical studies before that.

I'm gonna wait for the AstraZeneca or J&J vaccine.

[–]Rowannn 1 point2 points  (0 children)

I know it’s not quite the same but we’ve been using rna vaccines in livestock for years and not seen any issues

[–]-Reflux- 2 points3 points  (5 children)

Yes. I feel like no one, even my fellow lab mates, is concerned about this. Idk how to explain it it just seems so weird to me.

[–][deleted] 12 points13 points  (4 children)

If it helps, your cells will express viral protein from viral RNA in the context of an infection too. It’s not that different from an actual infection, except it’s rna that can’t propagate, and it’s just for the one key protein.

[–]-Reflux- 1 point2 points  (3 children)

I know how it works theoretically. It’s just weird to induce something like that intentionally. It’s like a scary type of exciting.

[–]CollateralKite 0 points1 point  (2 children)

CureVac's self replicating RNA is much more exciting to me, 1ug dosage because the RNA carries the machinery to copy itself.

[–]-Reflux- 1 point2 points  (1 child)

Isn't that a little sus in case of mutations?

[–]CollateralKite 0 points1 point  (0 children)

A little bit, but to date the experiments I've heard about don't have significant drift. Not my particular field in RNA so I can't find an exact number quickly.

[–]L-Acidophilus 4 points5 points  (2 children)

Also me, not buying any vaccine stocks before they are rising: 😢😭

[–]icatsouki 0 points1 point  (1 child)

Do you think they'll really rise that much?

[–]L-Acidophilus 0 points1 point  (0 children)

Moderna stock increases by 9.5% along with rise of S&P 500 and DJIA after the announcement about Moderna's vaccine.

I am not an expert or really into the stock market (not yet). But I would say that is a big increase if you own many Moderna stocks.

[–]catshoes23 6 points7 points  (4 children)

To my knowledge Moderna doesn't have the manufacturing capabilities to provide the number of doses required worldwide.

[–]rpolly18[S] 10 points11 points  (0 children)

They’ve partnered with Lonza I believe for manufacturing. It’s true that Pfizer definitely has a leg up in manufacturing, but I think moderna will not be that far behind.

[–]herbivicus95 17 points18 points  (2 children)

It would be foolish to assume we will rely on just one manufacturing capacity, I hope the vaccines will be outsourced in some way. And if not, then the Chinese will win the market - they are the only ones who will be able to make enough doses in such a short time

[–]catshoes23 6 points7 points  (0 children)

Absolutely, pretty sure they already have a deal to partner with AstraZenenca. Even with such a partnership it will likely take another year to manufacture enough doses for worldwide vaccine campaigns.

[–]icatsouki 1 point2 points  (0 children)

India has a lot of huge vaccines makers too I believe, will most likely be the source of vaccines sold to developing countries I imagine

[–]EL___POLLO___DiABLO 2 points3 points  (0 children)

First mover advantage in scientific publication is a thing

[–][deleted] 1 point2 points  (0 children)

ULT freezer manufacturers gonna have a hayday next fiscal quarter

[–][deleted] -1 points0 points  (8 children)

Pfizer released those results knowing full well that no PCP or GP will have a - 80 to store the vaccine. Marketing ploy.

[–]dorpedo 10 points11 points  (0 children)

It's standard to store RNA at -80

[–]sinnysinsins 3 points4 points  (5 children)

I heard on the WSJ podcast that they are developing portable -80C devices for distribution that each would hold a few thousand doses

[–][deleted] 2 points3 points  (0 children)

I think it’s fair to say they took advantage of the data they had from a marketing/publicity standpoint, but given the extremely tight timetable they were working with I would bet they wanted to play it safe and store the mrna vax candidate is colder temps to hopefully increase likelihood it would work.

[–]DankNastyAssMasterMS in Bioanalytical Chemistry 0 points1 point  (0 children)

Not that I know anything whatsoever about the clinical stuff, but wouldn't it make sense to distribute the Pfizer vaccine in urban areas where -80 storage exists, and the Moderna one in less populated areas where it doesn't?

[–]coolwali -1 points0 points  (3 children)

I'll stan whoever actually comes out with an effective vaccine rather than whoever has the best lab results

[–]icatsouki 0 points1 point  (2 children)

They all seem to be working well no? I don't remember hearing of one that was "disappointing"

[–]coolwali 0 points1 point  (1 child)

"Seem to be working well in trials" isn't the same as "is out and available to the public and is effective in practise".

There are no shortage of treatments that look promising at first but end up being less than optimal in the field. There's no point celebrating that a vaccine looks promising because there's no guarantee it will work when the time comes. So better to wait until one that actually works comes out

[–]icatsouki 0 points1 point  (0 children)

These are results from their use on normal people!

[–]deafening_mediocrityCancer Biology 0 points1 point  (0 children)

First come first serve for huggsies

[–]bottomlessLuckys 0 points1 point  (0 children)

if ya ain’t first, you’re last

[–]kondenado 0 points1 point  (0 children)

It's nice to know that unlike Pfizer vaccine you can put modernas in the shelf

[–]xvndr 0 points1 point  (0 children)

I’ll be honest I did not think they would be getting to phase 3 this quickly.