[pil4rin]

“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?

[Someone1234]

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.

[runsWphotons]

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.

[jefftk]

> 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.

[runsWphotons]

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.

[maxerickson]

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.

[kungito]

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

[nradov]

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.

[lenkite]

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

[revelio]

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.

[MAGZine]

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.

[runsWphotons]

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

[jewayne]

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.

[amluto]

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.

[tptacek]

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

[bluGill]

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.

[XorNot]

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.

[peteradio]

> 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.

[amluto]

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.

[revelio]

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).

[Eric_WVGG]

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).

[francisduvivier]

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.

[ABCLAW]

>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.

[weaksauce]

> 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.

[pixl97]

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.

[revelio]

Polio wasn't eradicated.

[palebluedot]

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

[wsc981]

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...

[aurizon]

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.

[ptdn]

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.)

[landemva]

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

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

[ptdn]

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.

[anshorei]

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.

[ptdn]

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.

[viraptor]

"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)

[gweinberg]

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

[ortusdux]

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.

[Izkata]

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.

[landemva]

> 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.

[klyrs]

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.

[xienze]

> 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.

[cmrdporcupine]

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.

[landemva]

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. My child and I were invited to the yearly pig roast for workers and family at one mine, and it was awesome. We then drove back to big city and unfortunately went to grocery store seemingly in a different world of masked gloved stink-eye scared shoppers wiping down their soup cans.

[cmrdporcupine]

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

[Madmallard]

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

[mjevans]

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.

[SoftTalker]

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.

[amanaplanacanal]

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.

[adastra22]

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

[elif]

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

[mc32]

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

[viraptor]

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

[Izkata]

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...

[viraptor]

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

[maxerickson]

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.

[peyton]

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.

[Touche]

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

[thallium205]

Here you go: https://twitter.com/pbhushan1/status/1451807240659161090/med...

[revelio]

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

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

[nomel]

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...

[animitronix]

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

[dannyw]

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

[CyberDildonics]

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

[jewayne]

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

[nomel]

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

And probably a semantic misunderstanding.

[b0sk]

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

[Madmallard]

Highly doubtful

[api]

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.