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Clinical trial of mRNA universal influenza vaccine candidate begins (www.nih.gov) similar stories update story
9 points by geox | karma 38372 | avg karma 9.12 2023-05-15 15:42:54 | hide | past | favorite | 192 comments



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“A universal influenza vaccine would be a major public health achievement and could eliminate the need for both annual development of seasonal influenza vaccines, as well as the need for patients to get a flu shot each year,”

So, one shot and no more flu? ever?


It does mention a hope for long-term durable immune response, but the point about being able to pre-emptively roll out a universal vaccine is probably more important. This would lower the total rate of infections by a lot and allow people to reliably get a useful vaccine without waiting to see which strains are dominant that year. (Also, an immune response doesn't mean complete immunity. mRNA Covid vaccines don't prevent you from getting Covid. It lowers the severity and spread.)

> mRNA Covid vaccines don't prevent you from getting Covid.

A couple years ago typing that would get accounts banned on most sites.


Don't look at me. I was screaming about COVID in January 2020. The lib moral panic changing directions on a dime without a change in intensity was disorienting.

Jan 2020 club checking in :-) I remember joking about a big pandemic being around the corner at my families New Year's party. Back then it was a few vague rumors from Chinese doctors that I was keeping an eye on but not taking seriously yet.

It's been crazy how much "always been at war with Eastasia/Eurasia" I've seen people around me engage in.


Social media delenda est. Reputation systems, politico-cultural tribalism, and human cognitive vulnerability w/r/t viral information have turned the entire cultural landscape into anarcho-1984.

That would be nice… recent history would tell us those claims are wildly optimistic.

It's easy to nay say, the COVID mRNA vaccines were great, it's nuts that people hold them to some imagined standard.

Like a single dose is less effective than multiple doses, especially if later doses are targeted at the circulating virus, but the first shot has an enormous protective effect, alerting the immune system to the type of virus.


Downvoted because the standard was not imagined; public messaging was blasted worldwide at EUA and revised downwards over time as more received the vaccine, damaging public trust in vaccination campaigns.

Can you link to some of that messaging where the claims were not met? Thanks.


That's been memory holed but here's a similar one:

https://twitter.com/ITGuy1959/status/1581034815700488192


The three that stuck out the most to me, that I very clearly remember, and hurt my trust:

Early in the pandemic, it was claimed that masks were not required. It was later admitted that this was to help the shortage, at the expense of the truth, and somewhat at the expense of the public [1].

President Biden went on national TV and bluntly stated, "If you get vaccinated, you won't get COVID." This was fiction, even at the time, with fact checks pointing it out the same day. [2]

Then later, "If you are fully vaccinated, you no longer need to wear a mask.", also fiction at the time, as the fact checks the same day pointed out [3]. There was no science to back this idea that vaccinations significantly reduced transmission, as it wasn't part of Pfizers tests [4].

Apparently related, some FDA officials resigned [5].

Things stated as fact that never should have been, and no attempt to correct it later, is what did it for me. There were many more small things that, appropriately, hurt my trust, and I feel a little crazy that people don't remember much of this.

[1] https://www.businessinsider.com/fauci-mask-advice-was-becaus...

[2] https://apnews.com/article/joe-biden-business-health-governm...

[3] https://www.politifact.com/factchecks/2021/dec/22/joe-biden/...

[4] https://www.factcheck.org/2022/10/scicheck-its-not-news-nor-...

[5] https://docs.house.gov/meetings/VC/VC00/20220429/114682/HHRG...


All accurate... what an absolute cluster the entire ordeal was.

Good to keep in mind, but also those are slightly different cases. One is a low number of very recent strains that mutated quickly, the other one is a large number of established strains we've been researching for ages.

SARS-CoV-2 still has one strain. The current vaccines are hyper-targeted at "variants", something much smaller than a strain.

Think of "influenza" like "dog", "strain" like "chihuahua" vs "golden retriever", and "variant" like "chihuahua with blue eyes" vs "chihuahua with brown eyes".

The distinction can get a bit muddied at the border* but I don't think we've reached that point yet.

*Like these dog breeds: https://www.countryliving.com/uk/wildlife/dog-breeds/a345060...


Good catch, thanks. Should've been more careful with wording.

Only if you vaccinate all the wild animals that carry it too.

*Until the flu variants mutate to be more vaccine resistant.

I'm pretty sure that's already the problem.

Viruses don't "resist" vaccines, because vaccines don't act directly against viruses. We're not talking about antibiotics here.

This is false: https://en.wikipedia.org/wiki/Vaccine_resistance

And probably a semantic misunderstanding.


Well that's how they make it sound, but they actually just said not annually.

But it doesn't make a lot of sense to me since influenza will be mutating to escape the immune response.


> But it doesn't make a lot of sense to me since influenza will be mutating to escape the immune response.

unless there is sufficient number of people that take it and it works well enough to eradicate it like say polio was.


Given the anti-vaccine resurgence, I think it is unlikely for the flu vaccine update to reach that sort of critical mass.

Especially now that governments don’t want to aid people financially that got harmed by the vaccines, since getting a vaccine was voluntarily [0].

It’s not like governments stated that the vaccines are both safe and effective and indirectly put pressure on people to get the vaccine, after all.

———

[0]: https://www-geenstijl-nl.translate.goog/5170466/ja-ja/?_x_tr...


Flu commonly comes from animal carriers, such as birds and swine, so I'm not sure if wiping it from humans will ever eradicate the disease.

Polio wasn't eradicated.

>But it doesn't make a lot of sense to me since influenza will be mutating to escape the immune response

Not all mutations are equal; the flu has antigenic factors that rapidly change in response to evolutionary pressure that don't significantly affect the fitness of the virus. If you're able to target another element of the virus that is conserved, or target a large segment of the possible antigenic conformations in a single vaccine, you'd force immune evasion mutations to significantly lower the virus's fitness, which is a very big deal.


The 18 variations are like a deck of 18 cards, the virus 'shuffles' one into use, next year another works better. The multivalent vaccine is for all 18 cards, evolutionary escape is far less likely, if not impossible.

Unfortunately the only real answer to that is: We don't have the data on either question yet.

Hemagglutinin has 18 subtypes, this style of vaccines are targeting them all, but we don't have data on how complete coverage will be (and or how common a mutation exists that could allow partial of complete circumvention).

We also don't have data on how long before the immune system needs to be retrained (aka re-vaccinated).

This isn't to foo-foo this vaccine; this legitimately could create a "universal" vaccine that could last years with only some minor reformulation every so often to catch new sub-types of HA.

TL;DR: This thing could be great. We'll need more data to know.


Is there any reason to think the immunity would last? Like is there evidence in animals? Because the one mRNA vaccine we gave had in people did not provide much immunity past three months. That was in environment of virus mutating, but so will the flu.

one thing that's important to remember is that there are degrees of immunity.

ending up with a cough is very different ending up in a hospital, needing a ventilator.

people forget that flu vaccines are important: many people die from the flu every year. even if flu vaccines don't 'last' in the sense that they might not stop you from getting any sort of sick, they almost certainly are effective in preventing major illness.


Sure, but there are still tons of questions and tradeoffs.

> the one mRNA vaccine we gave had in people did not provide much immunity past three months

That's much more about the virus than the vaccine type, no? The non-mRNA vaccines acted similarly.


I think it is both. The mRNA vaccine immunity did not wane just because of changes in the virus. That was probably a factor but in this case I don't think it was even the biggest one. The immunity just wanes, even to the same strain. It is to do also with the immune system itself.

The antibodies produced by any vaccination series wane, it isn't a surprise that it happened with the COVID vaccines. The mRNA vaccines do induce memory T cells, which is exactly persistent immunity, so the immunity doesn't 'just' wane.

Repeated doses of the vaccine broaden and increase the antibody response, so of course it makes sense to encourage them when infections are raging, and an annual booster will induce an antibody response, providing increased protection for a period of time, so of course it makes sense to encourage them, especially for more vulnerable people.

This inability to look at things in a sort of probabilistic sense, where things can be good without being perfect, is incredibly damaging.


If that was so then things like alergies and autoimmune diseases wouldn't be for life

The non-mRNA COVID-19 vaccines that targeted the entire virus rather than just the spike protein generally produced somewhat more durable immunity even after many mutations. In principle it might be possible to make mRNA vaccines that work in a similar way, so I don't think it's a fundamental weakness in the technology.

The non-mRNA vaccines did not give increased susceptibility to myocarditis AFAIK.

They did. The AZ vaccine was not mRNA based and was pulled from the market because it killed so many people.

The vaccines had two problems:

1. Spike protein is nasty. It causes clotting and organ damage. Doesn't matter how it gets in your body: virus, mrna, adenovirus, classical grow-it-in-eggs.

2. mRNA drugs specifically rely on special coatings which were as recently as 2017 unable to launch on the market due to toxicity that develops after multiple dosings. There's no evidence this problem was ever solved and Moderna pivoted from drugs to vaccines specifically because they couldn't solve it, the logic being that with vaccines you only have to take them once to get a lifetime of protection so the toxicity doesn't matter (doh).

https://www.statnews.com/2017/01/10/moderna-trouble-mrna/

mRNA is a tricky technology. Several major pharmaceutical companies have tried and abandoned the idea, struggling to get mRNA into cells without triggering nasty side effects

Three former employees and collaborators close to the process said Moderna was always toiling away on new delivery technologies in hopes of hitting on something safer than what it had. (Even Bancel has acknowledged, in an interview with Forbes, that the delivery method used in Moderna’s first vaccines “was not very good.”)

nanoparticles created a daunting challenge: Dose too little, and you don’t get enough enzyme to affect the disease; dose too much, and the drug is too toxic for patients.

Moderna could not make its therapy work, former employees and collaborators said. The safe dose was too weak, and repeat injections of a dose strong enough to be effective had troubling effects on the liver in animal studies.

The drugs it is pushing along now, by contrast, are more modest, relying on single administrations of mRNA.


"no annual" doesn't mean "just one". Lots of vaccines wear off after a few years and need a booster. (There's lots of people who don't know about it / don't get reminded and never get them)

So we'll only need them in election years? Umm, I mean leap years?

I'm not a doctor/immunologist, but as I understand it the flu shot targets 4-5 different strains. Each year they have to ID what they believe will be this season's leading strains, and then blend together the mix ahead of time. This takes a lot of work, and sometimes they get it wrong and 8th most common strain surges and it's a scramble to save lives.

So I think the promise of a 'universal' vaccine means one that would target all/most strains.


Yep, this is why you're supposed to get them every year - it's extremely rare for a new strain of influenza to appear (we're talking like 3-5 in the past century IIRC), but rather than attempt to have everyone keep track of which ones they've gotten the shot for, it's easier to just tell everyone to get the current one.

Because of this scattershot approach it's also not clear how long it actually lasts.

This is also one of the main reasons mRNA is supposed to be such a huge boon to vaccinations: one of the major reasons so few are targeted each year is manufacturing costs.


> you're supposed to get them every year

I'm physically active, no big health issues, and my Dr. says I don't need it.


That described me when I got a flu that kicked my ass with a high fever for a few weeks and career-impacting brain fog that lasted a couple of years. Your doc is right, you don't need it; you'll survive. But if your brain is your moneymaker, be warned that death isn't the only possible long term side effect.

No. The goal is one shot that doesn't have to change from year to year. We already know that the flu doesn't have a long enough incubation period for humans to gain lifetime immunity. Which means that even if this vaccine works and is effective against all flu viruses past, present, and future, it will probably still be a good idea to get a universal flu booster every year.

I’m not convinced that mRNA vaccines as they currently exist are well suited for repeated boosting against the same virus. See, for example:

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

And also the quite disappointing efficacy that the CDC reports for repeated Covid boosters.


Is the Covid issue mRNA, though, or is it how much of a moving target they were trying to hit with the bivalent booster?

The flu mutates more readily than COVID. With the sudden spread of COVID around the world we saw a few mutations, but the flu would mutate a lot more given the same spread. Most of us have some flu immunity though and that tends to limit spread, so it seems there are less mutations.

Right but that varies from virus to virus - the goal of a universal flu vaccine is to hit a well-conserved region of the virus which doesn't mutate much. Our inability to do it so far doesn't necessarily imply it's impossible.

Whereas most current COVID vaccines target the spike, and disappointingly the spike is a lot more malleable then hoped.


> Our inability to do it so far doesn't necessarily imply it's impossible.

It's a fairly solid indicator though that it must be tricky or that the body is making some tradeoff.


Or just that we can't stabilize/synthesize the protein usefully in a vaccine with existing techniques.

One of the big deals of mRNA is that because you get the proteins made in-vivo (in the body), you inherit all the body's machinery to do this naturally - after all, viral replication requires using that exact same machinery in order to replicate up the viral proteins in the first place.


The bivalent booster was pretty much on target in late 2022 and the beginning of 2023, and if it had been anywhere near as effective as the original two-dose series, I would have expected rather better results than this:

https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7148e1-H.pdf Table 3

These are somewhat less unimpressive (IMO) numbers here:

https://www.cdc.gov/mmwr/volumes/72/wr/pdfs/mm7205e1-H.pdf

https://www.nejm.org/doi/full/10.1056/NEJMc2215471

I don’t think one can draw a conclusion as to what exactly is wrong. IMO it’s too bad that Novavax flubbed their vaccine rollout so badly — it would have given valuable comparison data.


Conclusions are possible, the causes are known. You aren't going to get it from the CDC though.

The problem is the first round of vaccines caused immune fixation. The boosters failed because the body can't tell the difference between such similar proteins and made antibodies for the 2019 spike variant instead of the one the booster was targeting, thinking it already knew what to do.

This was covered up during approvals by redefining the success criteria as elevated levels of antibodies to "spike protein" without being specific about which one, and then ignoring actual effectiveness numbers (which were zero or negative).


IANAD, but another way of expressing that, by my understanding:

There are two major strains of the flu, and one or the other becomes the dominant strain every year; it's difficult/impossible to predict which. And due to the way vaccines are made (injecting the inert virus into unfertilized chicken eggs for replication), the annual vaccine has to be made off of one strain or the other.

This "universal booster," instead of targeting one strain or the other, would be able to immunize against most/all. That doesn't mean that it's a one-and-done vaccine like measles; it could still require annual renewal. But it would be affective against all strains, so you wouldn't find yourself with the flu despite getting the shot (i.e. what happens to me literally every year).


In practice: one shot or possibly one shot every few years and you have about 50-75% less chance of getting influenza. If enough people get it it could increase herd immunity further reducing your chances of getting it.

I’ll take it.

Antivaxxers will of course find some other explanation for the reduction in flu cases or point to the people who still get it as proof the vaccine doesn’t work.


> So, one shot and no more flu? ever?

Why even take a shot? If results from 2020/2021 are to be believed, all it took was some half-hearted masking to practically eliminate the flu from the face of the earth.


yes well it's not like there haven't been public health campaigns for decades asking people to wash their hands and not cough on each other and stay home when sick if possible... and people ignored them

It took a pandemic where people were basically a) scared for their lives and b) threatened with bylaw and legal ramifications, to actually get them to respond to civic health concerns and comply.


I was 'critical infrastructure' and didn't stay home. Work trucks kept rolling.

I wasn't scared. I didn't 'voluntarily' comply with operation warp speed. Visits to mine sites were glorious because MSHA didn't promote the OSHA theatrics.


... and.... I don't care?

Yeah masking was definitely not the reason. It was people staying home.

Sign me up for this, I want a shot that's got a reasonable chance of being effective even if I need it every year or two.

I'm the opposite. I have zero interest in this. I've never had a flu vaccine in my life. I've had the flu maybe once. And I'm nearly 60.

Some sort of natural immunity maybe? I realized several years ago that I was getting the flu every year unless I got the shot, and it always kicked my ass. I did skip the shots over the Covid years though.

On the other hand, I’ve managed to avoid getting HSV-1 even though it seems like everybody else in my age bracket (over 60) has it. Must be something genetic.


Yea, if there's suddenly no evolution in the universe.

Potentially. Especially the AI folded mrna vaccines which have an order of magnitude or better immune response and persistence.

Highly doubtful

I wonder if this would be a candidate for nasal delivery?

Why would it be and why would that be important if it's something you need once every few years?

It's the main point of entry to the body for respiratory viruses. If it works it's by far the best place to stop an infection.

The problem is "if it works": There's been a few attempts in the past and from what I've seen, none of them worked well.


How would an mRNA vaccine that works by directing cells to produce copies of a spike protein over multiple weeks, stop viruses from entering the nose?

Nasal vaccines are inhaled the same as a respiratory virus is inhaled. The theory is they'll trigger immunity in the same tissues the virus would first encounter, instead of letting the virus get a foothold in the respiratory system before reaching the rest of your body, where an injected vaccine would have built the most immunity.

The mRNA covid vaccine nasal trials are going very well, so I would assume a similar influenza vaccine might fare just as well. As to the why, there are few barriers to getting a flu shot, but these barriers definitely cut down on vaccination rates. If you take needles out of the equation, the whole thing becomes easier. Heck, I could see people being able to self administer a nasal spray.

Because people don't like needles.

Because the logistics is easier if you are trying to vaccinate the world.

Because you could dose yourself at home, maybe a daily microdose after brushing your teeth or a yearly round for the family when you change your smoke detector batteries.


I was hit hard by my first covid booster, and every traditional flu shot I've ever had has made me as sick as I've been from the flu itself (which is why I don't get flu shots anymore).

I wonder if an mRNA flu shot would be twice as bad, or better, in terms of impact on my health?


> which is why I don't get flu shots anymore

You could try one of the non-egg based vaccines and see if that helps with your side effects for example Flublok Quadrivalent[0]

[0] https://www.cdc.gov/flu/prevent/qa_flublok-vaccine.htm


Yeah, I might. Friends have suggested such alternatives to me as well. I'm not opposed, but I also am not highly motivated to try, because I haven't actually come down with the flu since my children grew up and moved out a couple of decades ago.

That's why the do these studies. But more seriously ask your doctor.

there's a lot of people that get a bad cold and think it's the flu. the actual flu can be insanely debilitating. (some get a lighter infectious dose and they escape a real bad case though)

I used to think I got the occasional Flu, until I actually got it... I was 30 then and it felt like I was dying!

I got covid in early 2021, and got the J&J shot at the end of the year. In both cases I had a fever, except the J&J lasted two days vs actual covid that lasted one. I have not been sick with covid since then.

I have never had a flu shot, and also never had the flu in over thirty years. I just don't see why I should get myself sick to risk not getting sick(er)? Anytime I mention this people call me antivax.

I was never skeptical about taking shots until the way the government handled covid. There is no chance I will take something that hasn't been thoroughly tested and proven to actually work the way our standard immunization schedule does.


As somebody who was in the Phase 3 clinical trial for the Pfizer vaccine in 2020, I was never skeptical about the intelligence of my fellow Americans until I saw the way we handled covid. It's an article of faith in Team Hoax that "COVID vaccines will eventually turn out to be bad", even though unvaccinated people dropped like flies throughout all of 2021 (forever the year of the Herman Cain Awards). 400,000 deaths that were preventable by the vaccines. smh.

As one of those unvaccinated people that got covid in 2021, I wonder if you're aware of what your actual odds of dying from covid were at the time. Bonus points if you break it down by age.

I'm not sure what probability dropping like flies equates to, but I think it's probably something pretty far off from reality.

Also, whatever your position on any of this, the whole Herman Cain Awards thing is not something to be proud of participating in. Even if you buy the line that not taking the shots was some sort of major crime against your fellow humans (pretty hard to argue at this point, but for the sake of argument) HCA was disgusting.


I maintain that the unnecessary death of 400,000 people due to misinformation was more disgusting, but hey, to each his own.

The unnecessary death of 400k people for any reason is indeed disgusting (even if those 400k were heavily weighted towards people who were at or beyond life expectancy, it's still tragic).

That doesn't make it any more admirable for smug redditors to celebrate tragedy. Do you really find that to be a compelling argument?


Whether you call it celebrating or properly recognizing, I feel they were doing a public service. Go back and read it, and you will see a distinct pattern, repeated literally hundreds of times. The same arc of (often vile) right-wing memes, conspiracy theories, and bravado, giving way to "tested positive, COVID is no joke", then to "calling all prayer warriors", and finally giving way to "X was the best, most generous person I ever knew". People who were obviously kind and good-hearted in their personal lives, but who had bought into, and propagated, the right wing disinformation loop.

A generation from now, when history majors in US universities take their required course on the COVID-19 pandemic, I expect that the HCAs will be required reading.


What was this public service?

The best interpretation of this that I can come up with is that somehow, HCA would shame some number of at risk people into getting the vaccine and saving their lives. I wonder, are you familiar with any estimates on number needed to treat to prevent a death? In other words, how many people would need to be shamed into taking tbe vaccine to save one life?

Realistically, it was a schadenfreude circle jerk. I obviously can't know this for sure, but I'm willing to wager that the number of people saved this way was negligible. It was just yet another place for the in crowd to shit on the out group and cheer each other on while they did it.


I already told you. When historians ask "Why did the US do so much more poorly in the pandemic than other first-world countries?" they will have a ready-made compilation of testimonials. This is tremendously important for future generations to know.

Did the HCAs convince large numbers of people to get vaccinated? Almost certainly not, because these people were way beyond convincing. Yes every single person working in the ICU saw an instance where an unvaccinated patient wanted to get the vaccine after they were already on their death bed with COVID. But beyond that, I think almost no Team Hoax people changed their minds about the vaccine.


Ok, so the public service was in "documenting" some scenarios of unvaccinated people dying, if they can manage to figure out what is actually real and what was just karma farming from an audience that is very hungry for exactly that kind of content.

And this will somehow be useful (tremendously important even) in the next pandemic.

We're just going to have to agree to disagree on this one. I think it's about as important as Fox news keeping old men angry and scared. HCA served the same purpose just for a different demographic.


Could it be possible that in the last 30 years you’ve had seasonal influenza and not recognized it, maybe a mild case? In my experience catching it a few times, there’s sick with the flu and siiiiiick with the flu.

But immunocompromised people and others most at risk can catch it regardless of how bad you feel - mass vaccination is for those people too, not just you.


Everyone has days when they feel kinda crummy, off their game, etc. I've always wondered if it's a super low-grade infection like influenza. No way to know without testing all the time.

Sure but knowing that the efficacy of the flu shot has been less than 50% for most years of my life (in my region) it seemed like a coin toss not to get it but a 100% chance of feeling lousy if I did.

> I just don't see why I should get myself sick to risk not getting sick(er)

If everyone acted this way, we'd never reach herd immunity with any vaccine-preventable disease, so yes, this is an anti-vaccine position. You're missing the fact that vaccines protect not just you, but the people around you.


> so yes, this is an anti-vaccine position.

Or, at the very least, it is a deeply selfish one.


It's a deeply selfish attitude for the elderly and obese (those most at risk from covid and influenza) to expect healthy people to take something that might have a net negative effect to them as individuals.

Children under five are at high risk from influenza. Even if you see nothing wrong with the antisocial and frankly eugenicist idea of letting the elderly and obese die off for want of herd immunity, you might consider the utility of keeping children alive so they can feed and change you in the nursing home.

Do you have an literature which suggests herd immunity is even possible for flu?

You can't reach herd immunity without a highly effective vaccine. No highly effective vaccine exists. If they manage to develop one, and if enough people get vaccinated, then herd immunity is possible. It's just math. The question is really whether a highly effective universal flu vaccine is possible to develop, and nobody knows that.

So you think it appropriate to preemptively call people antisocial eugenicists based on a hypothetical vaccine?

All of this discussion is abstract, based on a vaccine that doesn't exist yet, yes. It is possible to discuss eugenics in the abstract. And in the abstract, saying "It's a deeply selfish attitude for the elderly and obese... to expect healthy people to take something that might have a net negative effect to them" is eugenicist and antisocial.

> saying "It's a deeply selfish attitude for the elderly and obese... to expect healthy people to take something that might have a net negative effect to them" is eugenicist and antisocial.

Ok, but why? It seems like socially it cuts both ways. If I ask someone to do something they don't want to do and they refuse are they necessarily antisocial? How are you balancing the gains with the losses? It seems that your methods of accounting only value the most likely losers if there is no intervention.


Let's play hypothetical and say the people who are at risk are less than 1% then who is the selfish group? Less than 0.1%? Does that number ever cause you to switch positions or at an arbitrarily small number would the rest of the world be selfish to not get a medical intervention on their behalf?

No covid vaccine prevents transmission of covid, there's not even good evidence that it reduces transmission. Anyone I know who was vaccinated at this point has gotten at least one other person in their household sick. Should I just ignore this because someone who had something to gain from shilling the vaccines told you otherwise?

I'm not against vaccinations as long as there is evidence that they actually work.


> Anyone I know who was vaccinated at this point has gotten at least one other person in their household sick.

This is frankly not credible. You can't be surprised when people call you antivax when you are making claims that don't fit any of the available data.


I have enough empirical data to conclude it doesn't work anywhere near as well as they claim, and act on that knowledge. I'm not harming anyone by not getting a booster shot, despite the claims of the covid cult that what I'm doing is akin to murder.

Vaccines on a population level are less risky than the illnesses they prevent and generally reduce death and healthcare costs to society. This is true of both the flu and COVID vaccines. There's a nonzero chance that you'll feel worse with the vaccine than with the illness, there's also a nonzero chance that:a) someone else getting a vaccine has helped you not get sick and b) having gotten the vaccine could prevent serious harm in the case of illness. You can bet against those outcomes but your odds get worse and worse as you get older.

My gripe was them claiming the vaccine would prevent you from getting or spreading covid despite knowing that was not true.

It has now devolved to the vaccine will make covid suck less if you get it, there's a non-zero risk of complication from the vaccine, and lets just not talk about transmissibility.


The descent from "The vaccine is 99% effective and prevents transmission" to where we're at now was pretty eye opening. It sounded too good to be true and was.

Nobody has been held accountable for coercing (and worse) the US population based on bad data. I don't see any reason to trust the government going forward.


No one who understood the vaccine said that. But deniers still claim they did.

I recall government sources and pharma claiming >90% efficacy for the mRNA shots, which alone seemed absurd for a virus we knew was mutating at a rapid rate.

They also claimed you could not contract or transmit the virus if you were "vaccinated". Then redefined vaccination to fit their narrative. It took dystopian levels of misinformation for me to just lose all faith in the "experts". However honest their intentions may have been, to make claims you know aren't true is malicious at best.


From [1]:

> We're not sure, at this point, that the vaccine protects you against getting infected. We know for sure it's very, very good, 94 percent, 95 percent in protecting you against clinically recognizable disease, and almost a 100 percent in protecting you for severe disease.

I'm looking at this paper[2] released in the Lancet in Feb 2022 and very, very few of the efficacy figures against severe disease show 100% effectiveness, nor anything like it in the vast majority of instances. I could be reading that big table wrong though, but the findings section has this:

> For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1–15·4) in people of all ages and 9·5 percentage points (5·7–14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time.

so I don't think I have, but happy to be corrected. The figures are certainly higher against alpha, but not 100%, that's quite an overstatement, in my view.

[1] https://transcripts.cnn.com/show/CPT/date/2020-12-10/segment... Chris Cuomo interviews Dr Fauci

[2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6... Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression


Yeah, the parent comment illustrates a misunderstanding of how vaccines work.

> No one who understood the vaccine said that. But deniers still claim they did.

This is historical revisionism.

The Pfizer and Moderna Covid vaccines were approved for a single indication, and a single indication only. Prevention of symptomatic Covid.

From the Pfizer vaccine package insert:

> COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older. (1)

They were never approved for anything else because the trials were never designed to test for anything else.

https://www.bmj.com/content/371/bmj.m4037

In a functioning science, when reality (almost everyone got symptomatic Covid, regardless of vaccination status) conflicts with predictions (~95% efficacy in prenting symptomatic Covid), there would be some attempt to understand why the trials failed so miserably.

The obligatory Feyman quote comes to mind:

> For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled


The trials showed that 95% efficacy over the initial trial period -- about 3 months, as I recall. That wasn't a made-up number.

As time went on, it became apparent that while efficacy against symptomatic COVID faded quickly, efficacy against severe COVID (I believe defined by needing hospitalization) and also against all-cause mortality remained strong. You would have had them pull a life-saving vaccine from the market on a bureaucratic technicality? That's insane.


> You would have had them pull a life-saving vaccine from the market on a bureaucratic technicality? That's insane.

It is not a technicality.

There are no drugs, procedures, medical devices, or vaccines without adverse effects. It is always and everywhere a tradeoff between benefits and harms. If you intentionaly terminate a trial (breaking blindness is effectively terminating it), you cannot trade off the harms and benefits because you have no idea if there are harms, or whether the benefits last.

There were drugs, devices, procedures, and even vaccines, whose massive harms were only apparent years after they were approved.


> There were drugs, devices, procedures, and even vaccines, whose massive harms were only apparent years after they were approved.

However, in this case "massive harms" were incurred when people WEREN'T vaccinated. We do know, from data collected around the world, that the vaccine lowered all-cause mortality. We know that vaccine hesitancy led to hundreds of thousands of deaths in the US alone.

You're right about one thing -- it's a tradeoff. And in this case the benefits were huge, and if there has been some great harm, I've yet to hear of it.


> However, in this case "massive harms" were incurred when people WEREN'T vaccinated

Even if it was true, do you suggest dismantling the current FDA efficacy and safety testing because it worked in one case? Is this a serious approach to risk management?

> We do know, from data collected around the world, that the vaccine lowered all-cause mortality. We know that vaccine hesitancy led to hundreds of thousands of deaths in the US alone.

The sad thing is that we know no such thing. Early termination of the trial made it impossible to know the real risks.

For example, it currently appears that myocarditis is diagnosed in one in 5,000 to 10,000 otherwise healthy young males (16-19 year olds)[1].

The vaccine has zero benefit in this population group because Covid is so mild in this group. In Israel, for example, exactly zero otherwise healthy 16-19 year olds died or were in any serious condition due to Covid.

In older people, and other risk groups (cancer, diabetes, obesity), the calculus is obviously different. But there was no reason to vaccinate otherwise healthy kids using a vaccine that was not tested properly.

[1] https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.0...


From my understanding, the RCTs were never big enough to gauge the risks you're talking about in a statistically valid way. As your data suggests, even if the relative risk of myocarditis from the vaccine is very high, the absolute risk is quite small. Meaning that carrying on the RCTs for years would almost certainly have told us nothing of value.

> From my understanding, the RCTs were never big enough to gauge the risks you're talking about in a statistically valid way.

You can't know because the trials were cut short.

The RCTs were too small to detect that specific risk. However, the only reason it was discovered outside of the clinical trial was because the base rate of myocarditis for 16-19 year olds is so vanishingly low.

If the base rate was even slightly higher, much larger effects could not have been easily detected. Would you be able to detect an increase, say, of the diabetes rate in 1 in 100 after the vaccine has been released? what about 1 in 500?

It should be obvious that if your trials cannot detect adverse events that occur in 1 in 10,000, you should not vaccinate populations in which there is a significant benefit in less than 1 in 10,000.

> As your data suggests, even if the relative risk of myocarditis from the vaccine is very high, the absolute risk is quite small.

And sadly, a few thousand kids had their heart damaged (hopefully minimally) for no possible benefit whatsoever.

> Meaning that carrying on the RCTs for years would almost certainly have told us nothing of value.

BTW, hindsight is not a valid way to design vaccine safety studies.


It actually was a made up number because they didn't measure correctly. They classified people as unvaccinated even for weeks after they took the shots. This is guaranteed to inflate effectiveness. Norman Fenton has made this point repeatedly and even written simulations to demonstrate it. With the delay period they used you get to 95% effectiveness for anything, including water.

>> Anytime I mention this people call me antivax.

You should politely and directly point out to them that the "flu shot" is not a vaccine and referring to it as a vaccine is ignorant.


I was talking about both covid and the flu.

It's funny, flu shots can make you feel sick. That's your body reacting and your immune system adjusting.

But compared to actually getting the flu, you get to skip the part where the disease eats at your organs and rips through your body destroying things.

So yes, you may feel sick after a flu shot. But I consider the alternative makes it worthwhile.


The shot may not be technically as bad as the flu, but for me, it's plenty bad. I'm bedridden for about a week after them.

Since it's been a couple of decades since I've had the flu, the shot isn't worth the cost to me in burned PTO if nothing else.

But perhaps the mRNA one they're testing would be different. I'm also aware that it's probably not the vaccine itself that is causing my symptoms, but other ingredients and different formulations are available that I'm likely to tolerate better. I just haven't actually tried them yet.


I was about to say, one of the big things we are learning is that what we see as merely a respiratory disease is actually a much more generalized attack.

This is why we are seeing things like a 40% reduced risk of Alzheimer if you get yearly flu shots. Short term you can feel bad from the shot but long term you are much resilient to the actual Flu's impacts. It looks like this could be the same with Covid.

https://www.medicalnewstoday.com/articles/flu-vaccines-linke...


The ONLY thing you should take away from this link is the following:

> More research is needed to understand the biological mechanisms behind the results in this study. For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to a lower risk of Alzheimer’s and other dementias.


That is true to some degree. But I just picked the first thing that I could find related to that search.

But on going research is starting to point towards the possibility that these repository illnesses are doing more long term damage, especially to other organs and the brain. That said this is still very early days and it could just be something that looks promising at first but could be nothing. The paths being explored does seem plausible. More research and data is needed.

Reminded of Alzheimer's being linked to Aluminum, looks promising at 1st but turned into nothing.


Following link to Journal summary; 'and=65 years old by the start of follow-up.'

This is interesting and may warrant actual studies beyond lookback data mining.


Does a particularly bad reaction to a flu shot correlate with an equally bad case of flu, had you not gotten the shot? Or is it just random?

Right, but the flu shot is generally far from 100% effective: https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates...

Compound that with the fact many adults don’t actually get the flu that often and it’s not exactly a sure choice for most. I have a terrible immune system and I’ve gotten the flu once as a teen/adult and I’m nearly 35. Apparently the average is 1-2 times a decade.

A more effective, longer lasting vaccine would make it a lot more palatable for people.


> has made me as sick as I've been from the flu itself (which is why I don't get flu shots anymore)

#1 FEELING sick is not the same as BEING sick. Even if your perceived experience is comparable, almost certainly there's less long-term damage to your health from a controlled vaccine than from an uncontrolled viral infection

#2 Some selection bias is definitely in place here. Those times you got a flu shot you didn't subsequently get that season's flu strain that the vaccine was targeted for. Since you didn't get that season's flu strain, you have no idea how much worse it would've been if you didn't have the vaccine. (And if you DID get the flu anyway, then you DO know that it would've been even worse had you not had the vaccine).

#3 Getting flu shots isn't just for you, it's for your community. Even if you don't get sick from the flu or don't mind getting it, by passing it around you increase the risk to those more vulnerable than you - the immunocompromised, and the elderly.

Please continue to get flu shots. Your future you and the rest of humanity thanks you.


From the HN Guidelines:

>"Please don't use uppercase for emphasis. If you want to emphasize a word or phrase, put asterisks around it and it will get italicized."

https://news.ycombinator.com/newsguidelines.html


> Even if you don't get sick from the flu or don't mind getting it, by passing it around you increase the risk to those more vulnerable than you - the immunocompromised, and the elderly.

Isn't it backwards to ask the young to make health sacrifices for the elderly? Plus it seems influenza vaccines don't even reduce hospitalisation in the elderly: https://pubmed.ncbi.nlm.nih.gov/37045684/ .


#1: I'm fully aware of this. But the flu shot puts me down for 3-5 days, so the cost is not low.

#2: I haven't got a flu shot in over 15 years, and I also haven't gotten the flu. Before I gave up on flu shots, and after my children moved out, I never got the flu either. There's no actual selection bias going on with me.

#3: Which is why I'm hopeful about this mRNA vaccine. If I can tolerate that, I'm on board.

> and the elderly.

Not sure when "elderly" starts, but I may qualify.

> Please continue to get flu shots.

I would if it didn't cost me so much.


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Yeah, that's literally the point of the study, recruiting a small group of people to go first and see how it goes.

Why? I thought the science had evolved and clinical trials are no longer necessary for vaccine development?

The appearance of a clinical trial is critically important.

Just make sure it doesn't test any important endpoint. Not mortality, not severe morbidity, not infectivity, and so on.

Also, make sure to break blinding early, so that long term side effects cannot be deduced from the trial.

In cargo cult science appearance is very important.


I guess you're being sarcastic, but no, the COVID vaccines had clinical trials. My employer, a medical group in Seattle, had some of our staff volunteer with running the trials and others of us--myself included--were members of trials.

The major difference was that several of the steps went in parallel instead of sequence because there was the money, people, and will to do it.


I never said anything about COVID vaccines. Why even bring them up?

You’re not fooling anyone.

They always argue in bad faith and then feign ignorance.

May be surprising to you, now, and you may have forgotten the hell that was inflicted upon us but a lot of things were lost and a lot of lives were broken.

https://noagendaassets.com/enc/1684100123.718_supercutunvaxx...


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Then what exactly did you mean when you said, "I thought the science had evolved and clinical trials are no longer necessary for vaccine development"?

> The major difference was that several of the steps went in parallel instead of sequence because there was the money, people, and will to do it.

That not true.

Important steps were skipped or shortened.

For example, blinding was broken a relatively short time after the beginning of the trial. Participant were notified whether they were part of the trial group or placebo group.

This makes the trial useless for the possibility of long term side effects.


This feels like the kind of thing to include citations with, no?

> This feels like the kind of thing to include citations with, no?

I assumed this was well known.

https://www.npr.org/sections/health-shots/2021/02/19/9691430...

Edit: note that the NPR piece missed the more important problem. While some people in the placebo group decided to continue the study and not to take the vaccine, blinding was irrecoverably broken, and what is worse, they are self selected, so randomization is gone as well.


That link says that after the FDA authorized the shots, the study participants were offered them. Not that something was skipped _before_ authorization.

Not giving these people the shots would have been immoral, it was already clear that they were effective and safe.


>Not giving these people the shots would have been immoral, it was already clear that they were effective and safe.

It was not clear that they were long-term safe; there was not enough long-term data yet to discover this. And by unblinding, they made it very hard to gather such data.

Now that we have some such data, we see that indeed there are some non-trivial long term risks, such as doubling the risk of blood clotting in the eyes: https://www.nature.com/articles/s41541-023-00661-7 .


> Now that we have some such data, we see that indeed there are some non-trivial long term risks, such as doubling the risk of blood clotting in the eyes

Doubling a miniscule risk. Even if true, this is orders of magnitude less consequential than the benefit gained by giving people the vaccine, instead of maintaining the blind group.


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> That link says that after the FDA authorized the shots,

Yes, important steps were skipped or shortened for the unprecedented approval of these vaccines.

> Not giving these people the shots would have been immoral, it was already clear that they were effective and safe.

How can it be clear that they were safe if you haven't done any type of longer term followup?


> Yes, important steps were skipped or shortened for the unprecedented approval of these vaccines.

If true, this link doesn't say it.


It says they stopped after authorization. They mean Emergency Use Authorization. Which can only be given to unapproved modalities.

That is, they stopped blinding half a year before the vaccine was actually approved.


the covid vaccines were fast-tracked by the fda and iirc biodistribution studies were sidelined early on and the LNPs ended up accumulating in the uterus of women

mrna vaccines are a promising technology but LNPs being modeled after viral membranes do pose general dangers to the body as the full evolutionary dance of their development is something we may never know. seeing as membranes are, naturally, older than the receptors that have extended their functions, any contributions to 'tricking' host immune systems may have nasty effects at larger scales than would normally be given by natural infection. how they affect various molecular pathways can pose a multitudes of threats.

there have already been widespread discussions on this topic and many others by appropriate experts in a wide variety of professions, you can find some here:

https://lakaruppropet.se/international-conference-pandemic-s...


When flu infects a cell, the cell starts to make the virus subcomponents, and it then starts to build complete infectious virions. Usually the cell ruptures and all the complete virions start to look for their attachment part on the cell. With Covid 19 = the spike. With flu it is sialic acid = endocytosis = merges with and through the cell membrane. There are a number of subcomponents in a virus. When the cell bursts open, the cell can not longer continue making virions = all the parts of the cell spill out and the body deals with them as foreign = immune system absorbs them and also the adaptive immune system makes antibodies and memory cells learn all of them as separate antigenic particles for which it makes antigens. These parallel antigens give a broad and deep immune response - this happens with COVID or FLU = why the immunity of a true infection is stronger and longer lasting than a spike response. Measles is large, when the cell breaks it spills out a huge pack of fragments of many types = very long lasting immunity. Measles vaccine 14-20 year, which, so when the orthodox jewish groups had deaths among children who attended measles parties, they also had illness among older Jewish people who were vaccinated a long time ago. Later Jewish people do not take vaccines for religious reasons. An older cadre of Jewish people who had infections in youth did not get infected as their immunity was almost life long.

This could be a big deal if the new vaccines work well, especially if they work well in older people. Hope for the best.

This is an anecdote, but it’s true. I used to constantly get the flu. A friend who is doing research at UNC North Carolina, told me to start taking zinc lozenges and take zinc in general.

I have not had the flu or cold in 10 years. I did catch Covid, but I was not taking zinc at the time. Since my last Covid infection, I have not had Covid again.

You know getting these mRNA vaccines doesn’t make you healthier.


Of course the mRNA vaccines don't make you "healthier". Health isn't a simple one-dimensional scale. They make you better able to fight the virus they target.

As for not having colds, that's nice. I'm guessing you haven't had a lot of exposure to people with colds either. I hadn't had many colds for years either, until I had kids and they started preschool.


Oh well, be sick, what do I care.

This will be mandatory to keep your job in 3…2…1…

Not sure why this is being downvoted. If someone told me in 2019 that, to keep my job, I’d have to take some vaccine as a young healthy guy for something that has almost no chance of killing me, I’d laugh it off too.

Too much money in big pharma for them to not push for in order to “save lives”


Yeah, we shouldn't save lives if someone makes money off it. Better to let the innocent die before letting someone get paid.

there's a lot of insidious subversion in this message, i'll doubt that its your intention and try and explain it as briefly as possible

young people didn't need the vaccines, old people did. using fear, shame, and intimidation as a measure of public health was extremely nasty, should not have happened, and should not be repeated.

shutting down the economy to save the old people was a mistake, we borrowed money from people who aren't born yet and destroyed the economic future of our children. the resulting economic impact will have worse health impacts on those who are now young than the virus would have, as these two things are extrinsically linked

an age demographic was going to be sacrificed regardless of which kind of plan was chosen, the plan chosen sacrificed the young for the old and this is fundamentally backwards.


I'd be totally OK with companies withholding pay from people who refuse safe and effective vaccines for the flu while they are sick. Companies lose billions of dollars in productivity due to the flu every year.

And if the new vaccines are anything like the old ones they'll have almost no effect on that; https://academic.oup.com/cid/article/54/12/1778/455098 . Current flu vaccines slightly reduce the number of cases but have no effect on hospitalisations. And if you look at a chart of the amount of annual flu cases from before the flu vaccines were released to now, there's absolutely no notable overall reduction.

The hope would be that the new vaccines are drastically more effective.

The problem with assessing flu vaccine efficacy is that the uptake of the vaccine is so low because the flu vaccine often has significant side effects (it knocks me out for a day each time), and often doesn't even prevent you from getting the flu. At best, the flu vaccine as it is today, just reduces the severity of the disease (which is worthwhile for some populations).


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Phase I trial. "Is it safe". Not "does it work". That's Phase II. Phase III is "does it work at scale".

This is incorrect.

Phase I is “is it immediately dangerous?”

Phase II is assessing side effects at various dosages, to dial in possible dose ranges. There is some measurement of clinical effect here, to assist in dialing in dosages.

Phase III is does it work / what is the effect size.


I wonder if this will overcome the problem of traditional flu vaccines that they make people 4x more likely to catch non-influenza viruses: https://academic.oup.com/cid/article/54/12/1778/455098

The study itself warns it was a small sample set and thus a small number of infections, and at that level it's possible a number of cases of illness sufficient to change the risk ratio were missed in either arm of the study, since they were essentially self-reported. Furthermore, because it was a strictly pediatric study, it would be very iffy to generalize this to adults.

But let's go ahead and stipulate the conclusion is true. The takeaway message is not to _not_ protect against influenza, it's to find better ways of protecting us from the other seasonal respiratory viruses. Relying on viral interference as a way to avoid infection is like starting a fire in your house to avoid the wildfire outside.


That is one study in children. And it looks like the most plausible explanation would be that catching actual influenza confers resistance to non-influenza infections, which is inhibited by preventing influenza. And if that is due to stimulation of innate and intrinsic immune defenses then that would explain why children show a high signal for that. There's a whole lot which isn't clear about that, it isn't clear that it affects adults the same way. It isn't clear that it is conceptually possible to have an influenza vaccine which doesn't do that. And it isn't clear that is a net negative since influenza tends to be much worse than other respiratory viruses (up until a few years ago anyway).

If AI starts helping build mRNA vaccines, the computers may start programming us.

The negativity around this in kind of mind-blowing to me. I would absolutely love access to an effective pan-flu vaccine. I wonder if someday my fantasy of a universal Rhinovirus vaccine could become reality too. I can only hope.

> I would absolutely love access to an effective pan-flu vaccine

If they couldn't do it for Covid vaccines, what makes you think they will be able to fo it for imfluenza ?



The aim of the covid vaccine was to have it available as soon as possible. We still don't really have enough information about how it will mutate in the long term

Influenza is well understood by now and has had decades to research


The COVID vaccine reduced severity of COVID and greatly reduced mortality. It also reduced spread albeit to a lesser degree (moreso with earlier strains). I would call that a success and it likely saved millions of lives so far.

Unfortunately all those claims have turned out to be false when people looked more closely at the data and how it was collected.

For example: deaths. Look at the Pfizer RCT trial results. There were more deaths in the vaccine arm than the placebo arm. The extra deaths were mostly cardiac/clotting related.

There's a reason so many people are confused about this. Governments, academics and media conflate COVID-induced mortality and overall mortality because if they admitted that COVID vaccines could kill a healthy person, it would have led to lots of people at low risk from COVID to not take the vaccines, so they pretended that there are no side effects or only very trivial side effects. But that's not how it works. You have to weigh all the benefits against all the costs. Inject people with a lethal dose of battery acid and then claim the resulting deaths are all a coincidence, and you'll discover it's incredibly effective drug against COVID mortality! But that doesn't mean you actually solved any problem. It's just a statistical artifact caused by dishonesty about side effects.

For another example: reducing the spread. No it didn't. Firstly, again, the RCTs didn't even attempt to measure this because you can't. Think about it. So any such claims must rely on inference from dubious observational evidence. But secondly, the observational evidence says the opposite. If what you say was true then cases could not have been higher in 2022 when the majority was fully vaxxed than they were in 2021 or 2020, yet that is the case.

Those are just two of the problems with how the authorities work with the data. Even the apparent claims of effectiveness against infection in the early days turn out to be wrong because of a methodological error (deliberate or otherwise) in how the trials and observational data was processed. In reality the vaccines may never have worked.

It's all very unfortunate.



Why is it mind-blowing? People are worried that another ineffective vaccine is going to be forced on them.

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