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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.



Same. Infectious disease epidemiologist, and I am hyped about how cool this is.

I got the Pfizer vaccine.

This is such a huge step from some of our older vaccines, which had much higher side effect rates, relatively speaking. These vaccines were tested in large clinical trials, and we're seeing very few poor outcomes. And yeah, what's in this vaccine is so much more ephemeral than "This virus is...mostly harmless?"


That claim you’ve just made is completely inconsistent with evidence showing much higher side-effect rates for mRNA over traditional formulations.

Moderna has something like an 80% incidence of fever after the second shot. That incidence of side-effect is unheard of, but in the opposite direction you claimed.

Now, this isn’t dangerous, of course.


Talking about side effects that are of public health concern.

The smallpox vaccine could blind you if you touched the vaccine site and then your eye. It had a 1 or 2 deaths per million vaccines side effect rate.

The live-attenuated polio vaccine can revert to wild type.

"Moderna has a high rate of fever and soreness at the injection site" because it's doing it's job is a very different thing.


This really isn’t true.

A simple search through VAERs shows negligible difference between j&j and moderna/pfizer


But VAERS data also shows significantly more serious adverse incidents compared to other widely-distributed vaccines like polio and hepatitis B.


All that means is that COVID is different.

Also your use of the word "significant" is very suspect.


I didn't mean "statistically significant" or anything otherwise technical.

This is the data I pulled [0] (apologies to mobile users for the formatting, it's TSV):

    COVID19 VACCINE (COVID19) 8,507
    DIPHTHERIA AND TETANUS TOXOIDS ACELLULAR PERTUSSIS POLIOVIRUS INACTIVATED HAEMOPHILUS INFLUENZA B AND HEPATITIS B VACCINE (HEXAVAX) (6VAX-F) 29
    DIPHTHERIA AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE + HEPATITIS B + INACTIVATED POLIOVIRUS VACCINE (DTAPHEPBIP) 2,247
    DIPHTHERIA/TETANUS/PERTUSSIS/HEPATITIS B (DTPHEP) 8
    HEPATITIS A AND HEPATITIS B VACCINE (HEPAB) 256
    HEPATITIS B VACCINE (HEP) 5,991
With the query criteria:

    Serious: Yes
    State / Territory: The United States/Territories/Unknown
    Vaccine Products: COVID19 VACCINE (COVID19); DIPHTHERIA AND TETANUS TOXOIDS ACELLULAR PERTUSSIS POLIOVIRUS INACTIVATED HAEMOPHILUS INFLUENZA B AND HEPATITIS B VACCINE (HEXAVAX) (6VAX-F); DIPHTHERIA AND TETANUS TOXOIDS AND ACELLULAR PERTUSSIS VACCINE + HEPATITIS B + INACTIVATED POLIOVIRUS VACCINE (DTAPHEPBIP); DIPHTHERIA/TETANUS/PERTUSSIS/HEPATITIS B (DTPHEP); HEPATITIS A AND HEPATITIS B VACCINE (HEPAB); HEPATITIS B VACCINE (HEP)
    Group By: Vaccine Type
    Show Totals: True
    Show Zero Values: True
It looks like ~130m people in the USA have received at least one dose of any Covid-19 vaccine [1]. It's hard to pin down a number of Hep B vaccinations as of 2021, but it looks like about ~70m people had been vaccinated as of 2002 [2]. 91-93% of newborns in the USA have been vaccinated for Hep B every year since then [3], and I very roughly guessed that 3.5m babies are born every year in the USA [4]; at 91% of 3.5m over 20 years, that's very very very roughly 64m people vaccinated against Hep B since 2002.

So there have (maybe) been at least as many Hep B vaccines administered as Covid vaccines, and there have been 2500 more adverse events for Covid-19 vaccines than for Hep B vaccines. The difference is smaller than I remembered, so I regret saying it's "significant".

That said, we can compute 99% confidence intervals [5] for both of these (in R):

    library(binom)
    (cis <- binom.confint(
      x = c(8500, 6000),
      n = c(130000000, 134000000),
      conf.level = 0.99,
      methods = "agresti-coull"
    ))
    #          method    x        n         mean        lower        upper
    # 1 agresti-coull 8500 1.30e+08 6.538462e-05 6.358307e-05 6.723719e-05
    # 2 agresti-coull 6000 1.34e+08 4.477612e-05 4.331152e-05 4.629023e-05
So yeah, the difference between 4.5 per 100k and 6.5 per 100k is statistically significant. The two estimated distributions basically don't overlap at all (which you can confirm by looking at the percentiles).

You can add as many 9s as you want to the confidence interval size, and you will get basically the same result.

But I don't know if this is considered a medically significant effect size.

Edit: This is a back-of-the-envelope result. Please do not take it very seriously.

[0]: United States Department of Health and Human Services (DHHS), Public Health Service (PHS), Centers for Disease Control (CDC) / Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 - 4/10/2021, CDC WONDER On-line Database. Accessed at http://wonder.cdc.gov/vaers.html on Apr 21, 2021 1:31:17 PM

[1]: https://www.usatoday.com/in-depth/graphics/2021/01/14/covid-...

[2]: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5125a3.htm

[3]: https://apps.who.int/gho/data/view.main.80300?lang=en

[4]: https://www.cdc.gov/nchs/fastats/births.htm

[5]: https://stats.stackexchange.com/a/423964/36229


One note: VAERS is a voluntary reporting system, and not anything close to a census of vaccine side effects - it's notoriously unreliable. People are watching the COVID-19 vaccines like hawks (for excellent reasons), while there's no reason to believe the standard schedule vaccines are receiving anywhere near the same level of scrutiny.


I'm replying because I can't edit my post anymore. I'd like to know if I should be counting the "combined" vaccines like DTAPHEPBIP as "Hep B" vaccines. I have no idea, but it changes the result.


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.


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.


Medical science is slow - and vaccine science moreso, because it is careful. mRNA vaccines were struggling to find a use case.

A major pandemic like this is a huge, urgent shot in the arm, both in terms of money and motivation, that accelerates things.


> A major pandemic like this is a huge, urgent shot in the arm, both in terms of money and motivation, that accelerates things.

And even in terms of ... shots in the arm!


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-t...


Devil's advocate: why were they not successful in developing one against flu, but we're quickly successful when creating one for covid?


There's a well established alternative for flu already? It's like asking why electric engine cars have taken so long to overtake petrol cars; there's a giant existing infrastructure and well known protocols for flu already, so the risk/reward balances aren't great for the newcomer.


Otoh having an established baseline can help understand the efficacy and cost comparison (and time to market), and with new technologies you might want to play it safe?


An emergency like Covid is the ideal environment to dismiss all concerns about efficacy and cost. The risk to losing some money on a failed vaccine is negligible compared to the cost dragging out the restrictions even just a little bit longer than necessary.


Disclaimer: no education in biotechnology or vaccines, just an observer who likes to nerd out on information and think about them.

My understanding is that mRNA vaccines need a protein to target (since mRNAs make cells produce proteins). What makes SARS-CoV-2 particularly suited for this vaccine type was their spike proteins. My understanding it that the spike proteins are very unique to that virus type, was enveloping the virus and the human biology doesn't have something similar to that, so it was an easy (!) target for this vaccine type.

At least one of those conditions above may not hold true for <insert virus name here>, which can make it difficult/unsuitable for mRNA vaccines to target.

Again, I may be wrong (please correct me and give me the correct information if so), but this is my understanding.


I got the second Moderna shot and I didn't feel a single side-effect. Interesting how that works.




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