Clinical trial of mRNA universal influenza vaccine candidate begins
nih.gov
nih.gov
If they couldn't do it for Covid vaccines, what makes you think they will be able to fo it for imfluenza ?
Influenza is well understood by now and has had decades to research
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.
So, one shot and no more flu? ever?
A couple years ago typing that would get accounts banned on most sites.
It's been crazy how much "always been at war with Eastasia/Eurasia" I've seen people around me engage in.
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.
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...
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...
And probably a semantic misunderstanding.
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.
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...
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.
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.
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.
That's much more about the virus than the vaccine type, no? The non-mRNA vaccines acted similarly.
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.
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.
So I think the promise of a 'universal' vaccine means one that would target all/most strains.
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.
I'm physically active, no big health issues, and my Dr. says I don't need it.
https://www.science.org/doi/10.1126/sciimmunol.adg7327
And also the quite disappointing efficacy that the CDC reports for repeated Covid boosters.
Whereas most current COVID vaccines target the spike, and disappointingly the spike is a lot more malleable then hoped.
It's a fairly solid indicator though that it must be tricky or that the body is making some tradeoff.
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.
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.
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).
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).
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.
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.
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.
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.
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.
I wonder if an mRNA flu shot would be twice as bad, or better, in terms of impact on my health?
You could try one of the non-egg based vaccines and see if that helps with your side effects for example Flublok Quadrivalent[0]
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.
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.
That doesn't make it any more admirable for smug redditors to celebrate tragedy. Do you really find that to be a compelling argument?
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.
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.
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.
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.
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.
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.
Or, at the very least, it is a deeply selfish one.
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.
I'm not against vaccinations as long as there is evidence that they actually work.
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.
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.
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.
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.
> 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
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
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.
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.
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.
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...
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.
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.
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.
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.
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...
> 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.
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.
This is interesting and may warrant actual studies beyond lookback data mining.
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.
#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.
>"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."
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/ .
#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.
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.
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.
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.
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.