Which is so unfortunate given the potential mRNA vaccines and therapies have.

They would have made fighting flu so much easier (for the context current flu vaccines take a lot of time to be made each season and hence not very agile towards dominant strain and sometimes miss it a lot, mRNA potentially improves this).

I would have liked to see some actual studies of whether multiple doses, over the course of years, of mRNA vaccines are a good idea. Take a look at:

https://www.science.org/doi/10.1126/sciimmunol.adg7327

and related papers. Is the propensity to generate IgG4 antibodies specific to mRNA vaccines? Is it a problem? It seems entirely plausible that an mRNA flu vaccine would look amazing for one season and less amazing years later. Or not.

The COVID vaccine trials were very focused on the efficacy of a 1-3 dose series, in people with no previous immunity, at preventing disease or reducing its severity over a period of weeks to months after the vaccine series. This is not at all the situation with influenza or the situation now with COVID.

Compare to vaccines like MMR or Varicella, which were, and still are, studied over a period of many years.

This is fascinating study, thanks for sharing!

It definitely brings questions about repeated mRNA vaccinations (and mRNA therapies I guess then too?).

Good thing repeated boosters for COVID shouldn't affect other diseases if I understood the study correctly (since target protein is different). Can be an issue for flu vaccines for sure (or it's not since protein used slightly different year to year?).

But answering this question is exactly why public funding is so important. If you're concerned about mRNA having long-term downsides, then continued government funding is exactly the right mechanism to force manufacturers to conduct the long-term studies you'd need to figure it out. It does not seem like it's necessarily in the manufacturer's interest to do these studies, if they're using their own funds and trying to turn a profit.

> Is the propensity to generate IgG4 antibodies specific to mRNA vaccines? Is it a problem? It seems entirely plausible that an mRNA flu vaccine would look amazing for one season and less amazing years later. Or not.

Flu vaccine effectiveness has been trending slowly downwards for about a decade. I don't recall any established reasons for it, though.

>Which is so unfortunate given the potential mRNA vaccines and therapies have.

There's what should be a glaringly obvious lesson about ends and means here but nobody will learn it.

The problem I've had with MRNA vaccines is that we decided a lengthy multi-year trial protocol was necessary to ensure vaccines are safe and effective.

Then COVID hit, and suddenly we decided to rush MRNA [1] vaccines into mass production without those protocols. Moreover, at one point they wanted to force [2] them on the population.

The thing that bothered me most is the government passed a law to prevent people from suing for damages if they're hurt by COVID vaccines [3]. If the vaccine really is safe and effective, why was the waiver necessary?

[1] If the made the COVID vaccine the same way they've been making them since polio, I'd be less uneasy -- if you made 25 vaccines with the process and they all worked okay, saying "it should be fine" for the 26th one is backed by some evidence.

But given MRNA vaccines were brand-new with the COVID ones, until then they'd made 0 vaccines with the process; saying "it should be fine" for the 1st one seems to be rather irresponsible.

[2] In my opinion, "you're being forced to do X" is a fair description of the situation if you have to show proof you did X if you want to get a job, get an education, or get on an airplane. Around the time of the first vaccines getting rolled out, these policies were being discussed very seriously.

[3] https://www.cnbc.com/2020/12/16/covid-vaccine-side-effects-c...

> The problem I've had with MRNA vaccines is that we decided a lengthy multi-year trial protocol was necessary to ensure vaccines are safe and effective.

I, actually, agree on this. It was hard balancing act of protecting the population (quite successfully I will note) vs lack of perfect certainty about safety. I've read there've been clinical trials of other mRNA vaccines in mid 2010s so there've been some research data available.

Now, on other hand, we have a lot of data to dig into and seemingly to prove safety of the vaccines.

> Moreover, at one point they wanted to force [2] them on the population.

Yeah, I think this wasn't a good idea. Especially after it was clear we're not getting full protection and covid turning to be endemic.

> If the vaccine really is safe and effective, why was the waiver necessary?

Balancing act mentioned above protecting suppliers, won't be surprised if it was part of negotiations between government and vaccine manufacturers.

I think we can see mRNA vaccine are mostly safe (and we'll get even better certainty about it as time passes) which is given how cool the technology is opens up a lot of opportunities.

The thing I wish was more understood in anti-mRNA vaccine circles was how mRNA vaccines work vs traditional vaccine platforms.

Personally, I feel safer taking mRNA vaccines. (And definitely an apples-to-apples novel mRNA vs traditional vaccine!)

Simpler and consumed, so fewer chances for things to go wrong via adverse immune system reactions.

Yeah, mRNA vaccines to old style vaccines are similar to hardware + software vs analog machines of the past. Cool and "simple" tech. However there might be unintended consequences we need to study - for example from a comment above: https://www.science.org/doi/10.1126/sciimmunol.adg7327

> The thing I wish was more understood in anti-mRNA vaccine circles was how mRNA vaccines work vs traditional vaccine platforms.

My experience actually looking at these groups is they did understand it better than most. The various studies people are pulling up in this thread today, showing more research is needed? They were sharing and talking about similar studies in 2021 and 2022 during the period everyone else was blindly repeating the "safe and effective" mantra.

Quick edit for an example of one of these earlier studies they were sharing: https://www.mdpi.com/1467-3045/44/3/73

HN isn't representative of the general population.

Very few people who I talked to outside of HN could give me a coherent definition of a randomized controlled trial.

I'm all for people being curious, but the catch in modern society is that people also need to be honest about their own ignorance.

Because faux curiosity being used to mask discomfort in ignorance is a recipe for bad outcomes.

The right's "rushed into production" talking point is especially amusing given their other messaging about cutting through government red tape. It's all just vibes.

We had a disease killing 10000s (if not 100000s) people in the country and you think government shouldn't adjust their regulatory framework to it? I would be very unhappy if they did not, government suppose to be conservative, but not that conservative. Calling this "just vibes" is very hypocritical in my opinion.

Right, my point is that we did appropriately cut through red tape when it became important to do so. Which (1) weakens arguments that complain about red tape and (2) exposes hypocrisy about claiming to oppose government red tape but then taking a bad faith stance about the vaccine being "rushed".

Gotcha, so you were criticizing right's hypocrisy on "rushed to production". I misunderstood you and got it opposite way.

One factual note here: mRNA vaccines were not brand-new with the COVID ones. The first human clinical trials using an mRNA vaccine were conducted in 2013.

  > But Trump's Base decided for Trump about this issue. Trump leads from behind on this one.

1. The base doesn't decide out of thin air, the USA audience have been primed for decades with `government = bad` (anything `social = bad` really). We have evidence of orchestrated anti covid campaigns on Twitter, but the soil was well prepared for it.

2. Trump always leads from behind. He is allowed some personal space and he uses that for personal profiteering. He flip flops on all important issues, policy does not interest him and it is way too difficult for him anyways. He gives public performances when he thinks it buys him respect.

3. If the public stops focusing on Trump's drama, they could regain bandwidth to make a proper analysis. But they need the help of an oligarch owned press, staffed by people who, like the general public, have to unshackle some self-harming beliefs.

Vaccine skepticism (and the broader medical skepticism) is a weird one though.

Because it's patently counterproductive -- modern medical science saves lives.

So what you really have is a bunch of people getting riled up about something because they don't currently need it, then making dumb choices at critical moments, then denying their actions caused consequences if they have bad luck.

A partner was a critical care nurse during COVID, and said she had people dying in beds who still denied COVID existed. Mind-boggling.

It is weird, but what we do know is that is surprisingly easy to compel people into self-harm.

  > Patently counterproductive 

Yes, but that is the gist. What you have got is the problem of the few who fear the numerous. Where you have power and wealth concentration, there will be a push to autocracy. Zero sum. Might makes right.

It is an international phenomenon, where (political) organizations and people copy and sync each others playbooks. Look at the Brexit, look at Orban, look at the tariffs, look at expelling talent and science, look at the killing of the free enterprise.

Fundamentally, parasites don't care about the host. If the host dies, they jump on the next one. That is why the Kremlin focuses on Ukraine and the rest, while the USA starts to talk about Greenland and Canada.

For normal people it is too crazy to believe, so we don't believe it.

> Where you have power and wealth concentration, there will be a push to autocracy.

Agree, though I think the why/how is interesting.

In watching it play out in several countries: (1) wealth concentration builds resentment against a minority (wealthy/elites) by the majority (poor), (2) someone from the wealthy/elite hijacks the majority dissatisfaction by saying they'll "get" the minority, (3) democracy sweeps that someone into power, (4) turns out, anyone wealthy/elite doesn't really give a shit about egalitarianism, and enriches themselves

I mean, when Brits vote in Boris Johnson or Americans Trump, do they really expect either to compromise their own wealth for the good of the nation, when it comes to that?

> Vaccine skepticism (and the broader medical skepticism) is a weird one though.

I don't think we have effective language to talk about this stuff.

You saying "vaccine skepticism" (or the real boogey man, anti-vaxxer) could mean anything from person who thinks the Jews are injecting microchips into us all, all the way to a person who has gotten all sorts of vaccines except for specifically the mRNA ones.

Obviously, these two people are very different cases.

In a discussion about cars, someone could say they wouldn't buy a Ford, and nobody feels the compulsion to call them anti-car. (And they probably actually understand some details about the car beyond eli5 marketing materials. Perhaps that explains it).

By vaccine skepticism, I mean biologically-ignorant people who latch onto vaccines as their cause du jour.

Yes, there are educated people and educated reasons to be skeptical of vaccines.

But in practice, at least in America, that represents a small portion of the entire vaccine skeptical community.

Skeptical seems an accurate description too, as most of them couch their beliefs in "Well, I'm just asking the question"ism.

Through and through anti-vaccine people are a smaller group.

> biologically-ignorant people

What does this mean? People who don't know a lot about biology? That's effectively everyone who isn't a biologist (and probably even some who are), which is effectively everyone.

> who latch onto vaccines as their cause du jour

That sounds like more than skepticism to me.

> But in practice, at least in America, that represents a small portion of the entire vaccine skeptical community.

I have no way of evaluating whether this is true beyond gut feelings. Do you?

>Vaccine skepticism (and the broader medical skepticism) is a weird one though.

We, as people, are much more sensitive to loss because of action over loss because of inaction. Doing nothing at the risk of getting sick sometime later doesn’t feel as risky as choosing to go take a product with risks, even though the risks are a million times lower than if you get sick. Taking a vaccine feels like you are doing something risky. It is distantly related to the trolley problem.

  > The vaccines were developed during the first Trump administration. Trump himself wanted credit for developing them.

No. They were produced at scale during his administration to combat the pandemic, but were developed well before that, with support from a government actually funding vaccine R&D:

Moderna was also awarded a $25,000,000 grant by DARPA through a program Autonomous Diagnostics to Enable Prevention and Therapeutics: Prophylactic Options to Environmental and Contagious Threats (ADEPT-PROTECT). Its stated goal was to develop an mRNA vaccine with the capability to suppress a global pandemic within 60 days. (2013)

The history of DARPA funding mRNA vaccine platforms should be more widely known, because it's exactly what the government should be doing.

DARPA identified novel pathogens with pandemic potential as a key threat to the US (and everyone else), identified mRNA vaccine platforms as something that would allow more rapid responses to novel pathogens, and invested in it.

And then when exactly that happened -- there were mRNA vaccine platforms ready.

When the crackpots learn DARPA funded Moderna's development of mRNA vaccines ahead of COVID19, all they hear is the government caused the pandemic.

And so has the amount of plastic in our biosystems and brains. And increased PFAS chemicals in various ecosystems. Soon with increased air overall environmental pollution in the US due to regulations being removed from various industries.

But... no relation to cancer at all, right?

There's also been an increase in wildfires since Pluto lost its status as a planet. Public info!

Number of cancer patients and cancer related costs were increasing since forever.

Post hoc ergo propter hoc.

The medical community, the government, and the media in general hid, downplayed, and censored discussions about the negative side effects of mRNA vaccines. Thus creating an aura of suspicion around the mRNA vaccine and loss of trust in the medical community.

Once they publish tons of trustworthy research on the side effects of mRNA vaccines, then people will have confidence in them.

> trustworthy

Yes. It will probably take years to decades for the medical community to regain the trust and confidence of the public. But keep doing good work and it will happen probably.

The problem with mRNA vaccines is that we did not downplay and censor charlatans enough. We allowed anti-vax rhetoric to spread like wildfire on Twitter, Facebook, and the like. Our scientists and doctors actually humored these people, and that was a huge mistake.

As soon as you tell an anti-vaxxer something like "there are risks, but..." all they hear is "aha!! I knew it was poison!".

Nobody on planet Earth said that the vaccine was 100% safe, nor that it was 100% effective. Because no vaccine, and no medicine, is. But we allowed people to revel in their own fear and anti-establishment mentality, and because of that, a lot of people died that did not need to.

My understanding is the mRNA vaccines are (1) the best hope for developing a fast vaccine in the face of a new, really-dangerous virus, and (2) incidentally a great hope against cancer. I'm sure this doesn't mean the end of funding for those other things, but I imagine it means less funding.

Why do we need to engage in ideological discussions and feelings about the mRNA vaccines?

Can somebody just post a link to the double-blind, placebo-based safety study of mRNA vaccine (e.g. COVID-19), to put this to rest once and for all?