Is there ongoing work here I'm missing? What progress has been made? I'm somewhat surprised that almost a year on from the initial vaccination roll-out in the UK we're now dishing out boosters which are .. identical to the vaccinations given out initially.
There's plenty of evidence that current vaccines work against variants:
- https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e4.htm
- https://www.nejm.org/doi/full/10.1056/NEJMoa2108891
- https://www.cell.com/cell/fulltext/S0092-8674(21)01057-6#%20
> given that original antigenic sin is a long known and well documented phenomenon?
This could apply both to vaccines and natural infections. Not sure what you are trying to say?
Is there any reason to be afraid of getting vaccinated?
There's plenty of reasons, do you mean to also ask how likely other people on the internet believe each one to be?
For example, if you ask me, this is my personal assessment:
Reason 1 - Vaccines could also contain microchips or other device for tracking, brainwashing and remote manipulating my body and mind by whoever mastermind is in charge of what goes in them.
I think that's very unlikely, I'd give it a 0.00000001% probability. I just dont know of any possibility for such advanced technology. And I can think of many different means that you can be more cost effectively tracked, manipulated or brain washed. I can also think of other ways they could have injected you with such things.
Reason 2 - The vaccines will result in worst long terms negative effects on your health than getting Covid.
I think this is a little more likely, but given all prior vaccines have shown to be quite safe, and even if they could be responsible for some long term effects, even some we haven't linked back to them yet, seeing as life expectancy and quality of life has grown year over year since the introduction of vaccines, it seems the equation would still play in their favor.
There are also more and more literature linking prior viruses as a possible cause of long term negative effects like dimentia, various auto-immune diseases, etc. So it would seem Covid is more likely to introduce long term negative effects.
So I'd give it a 1% chance.
Reason 3 - The vaccines will result in worst short term effects on your health then getting Covid.
I think this one has been shown that most of the time, Covid is more likely to kill you or make you really sick as compared to vaccines.
I'd give this one a 0.0001% chance.
Reason 4 - Vaccines can stop your pregnancy or your period and make you stink
I have seen zero cases of this, and everyone who's had a vaccine to my nose do not smell, and still have period and can get pregnant.
I'd give this one a 0.000000000000000001% chance.
There might be more reasons, but those are the ones I've heard most often, and this is only my personal risk assessment.
The one point I'd add some clarification to is your .0001% chance of the vaccine having worse short term health effects. It's not that the number is wrong, exactly, it's that it's an average. It's contingent on a host of factors, but once you learn how rare side effects are, it's tempting to rhetorically bludgeon people with concerns over the head with this, even though in some cases they don't deserve it.
To give the most obvious example [1]:
> Some advisers were concerned that young and healthy Americans who don’t need a booster might choose to get one anyway. Side effects are uncommon, but in younger Americans they may outweigh the potential benefits of booster doses, the scientists said.
> “Those that are not at high risk should really be thoughtful about getting that dose,” said Dr. Helen Talbot, an infectious disease expert at Vanderbilt University.
That's pretty strong language suggesting that if you are (1) young, (2) healthy, (3) already vaccinated, the risks might outweigh the benefits of getting vaccinated again (getting a third shot). That's extremely limited, of course, but it's important not to neglect the striking degree to which contingent facts can modulate the cost / benefit analysis.
[1] https://www.nytimes.com/2021/10/21/health/covid-vaccine-boos...
> I have seen zero cases of this, and everyone who's had a vaccine to my nose do not smell, and still have period and can get pregnant.
> I'd give this one a 0.000000000000000001% chance.
VAERS is tracking the following:
17,128 DEATHS
83,412 HOSPITALIZATIONS
92,017 URGENT CARE
127,641 DOCTOR OFFICE VISITS
7,532 ANAPHYLAXIS
10,179 BELL'S PALSY
2,631 Miscarriages
8,408 Heart Attacks
10,304 Myocarditis/Pericarditis
26,199 Permanently Disabled
3,875 Thrombocytopenia/Low Platelet
18,925 Life Threatening
31,753 Severe Allergic Reaction
9,734 Shingles
2,631 Miscarriage
15,158 Menstrual Disorders
5,401 Vaginal/Uterine Haemorrhage (All Ages)
The key question about VAERS data is, how bad is the under-reporting of side effects? The allegations of under-reporting ratios are all over the place, from as low as 1 to 3 undercount, to as bad as 1 to 100 undercount.
We really don't know how bad the situation is, or isn't. We just know there are side effects and some of them are non-trivial.
https://vaers.hhs.gov/data/dataguide.html
Also, where are you getting your numbers. When I search the database (after agreeing several times that I read and understood a disclaimer similar to the above), I found 8,225 reports of death
Though to be fair, and again, I'm a random person online explaining my personal assessment, but in my assessment I also take into account that I assume that smarter people then me have already ran all these numbers, and maybe I'm naive to assume that, but I also don't have the time, know how and the access to all the data I'd need to do so myself.
In that case, I have to either trust institutions and academics of multiple countries who seem to mostly agree +/- a few difference, or I have to trust volunteer effort from generally amateurs on the internet mixed in with some legitimate trolls. And since in my field of expertise, I see often that the internet is filled with more crap than accurate information, I don't really trust the internet as much, especially the information that's easy to find.
We also know that the usual mechanism for bad reactions to vaccines is allergic reaction, which is easily observed on a short timescale, and basically doesn't happen with the covid vaccines.
The question is really fundamentally simple for a massive vaccination campaign
Expected injury rates as a % of the population
Actual / Reported injury rates as a % of the population
Even while accounting for the low likelihood of even receiving reports of things.
We already know that some of the injury reports coming in have been independently verified by other nation's health departments. After all, there is a reason for some of the vaccine pauses among the young and healthy in the nordic countries.
Those would not be in VAERS. At all.
Everyone, go get vaccinated, please.
A friend of mine that happens to be a medical professional in a European country told me of the clotting related issues starting to show up in their own numbers far in advance of it being likewise confirmed in VAERS too.
That is why we know about these issues.
Country A and Country B have problems that show up, they ask which vaccine, which vector, etc, and they draw conclusions.
Reason 5 - Quality of vaccine, freshness, poor QA, defective dose
I think this is a likely concern in some countries. The vaccines are challenging to transport and properly keep stable and manufacturing of them happens in many places and was put in place and scaled up very quickly, quality control could be an issue, same as proper transportation and storage.
I would honestly give this one a 5% chance.
Argument goes along the lines that "all" previous coronovirus vaccines were found to have ADE effects. It took a long time for them to show up, but the effect was large and the trials were abandoned.
So apparently we're still all going to die. Spring/Summer 2022 (northern hemisphere time) will be the cataclysm.
I'm inadequately gnorant to evaluate the argument on merits, but I find it interesting because it fits the classic definition of "bullshit".
Didn't tens of thousands of trial participants get covid vaccines back during July to September last year? They're still monitored I think. If what you said is true then they should be dropping like flies which they are not.
> Pfizer intentionally wipes out the control group as soon as they can by vaccinating all of the kids who initially got the placebo. They claim that they are doing this for “ethical reasons”. But everyone knows that Pfizer’s true aim is to wipe out any comparison group so that there can be no long term safety studies. Wiping out the control group is a criminal act and yet Pfizer, Moderna, J&J, and AZ do this as standard practice with the blessing of the FDA/CDC.
https://tobyrogers.substack.com/p/ten-red-flags-in-the-fdas-...
The vaccine was effective/safe enough that it would cause more harm to leave them unvaccinated. If anything it means that there's more points of safety data by doing it this way.
> COVID-19 rates in children ages 5 to 11 are so low that there were ZERO cases of severe COVID-19 and ZERO cases of death from COVID in either the treatment (n= 1,518) or control group (n= 750).
My intention is not to spread it, but to describe it because I think it's useful to understand the narrative. You cannot disagree with something you do not understand.
There's a faction of resistance which is neither shrill, nor obviously stupid, and they have coalesced around a narrative that is constructed in a way to be very compelling and frightening.
It's either an elaborate effort, or it's the natural result of smart people not trusting evidence, and extrapolating into authoritative-sounding "maybe"s.
In short, classic "bullshit".
But it would take someone more learned than I, to argue on merits. The promulgators of this narrative have read the Wikipedia article on ADE, and insist that that narrative is flawed, for reasons I cannot contradict.
Personally, I don't believe it for a second, but my reasons are rather prosaic: IME the more elaborately-cooked the future scenario is, the less likely it is to happen, outside of fiction. Nature tends toward the non-dramatic. I expect to be proven correct over the next ~year.
Not just bullshit, but millennialist bullshit!
I am asking specifically if there is any hard evidence of vaccine effectiveness to back statements made by biopharma corporations about variant-specific vaccines, for example:
"We have built a process that within 95 days from the day that we identify a variant as a variant of concern, we will be able to have a vaccine tailor-made against this variant," [Pfizer CEO] Bourla said.
https://www.insider.com/pfizer-ceo-vaccine-resistant-coronav...
Yes, we all know that. Follow the scientific literature and you will find updated vaccine assessments soon after a concerning variant is noticed.
> "We have built a process that within 95 days from the day that we identify a variant as a variant of concern, we will be able to have a vaccine tailor-made against this variant," [Pfizer CEO] Bourla said.
That's likely closely guarded IP, so I don't think there is hard evidence for that statement. But the phase I clinical trials for Moderna's [1] and Pfizer's [2] started respectively in February and April 2020, just a few months after covid became a problem. This is IMHO reasonable evidence that 95 days is a plausible lead time.
"Original Antigenic Sin: How First Exposure Shapes Lifelong Anti–Influenza Virus Immune Responses"
And in case it is not clear, in this thread I am not advocating neither for or against vaccines, so we can end it here unless you have something of substance to add.
In terms of long term protection, I don't think we really know yet.
In terms of long term side effects - do we know of any past vaccines with notable side effects that only became known after 12+ months? Genuine question.
A picture from a recent preprint of 600k veterans over 6 months shows troubling VE against infection curves. J&J VE against infection is gone. Pfizer curve is just 2 months behind, at 53% and dropping.
https://www.medrxiv.org/content/medrxiv/early/2021/10/14/202...
https://www.medrxiv.org/content/10.1101/2021.10.13.21264966v...
Fortunately VE against severe infection holds much better at 77% Pfizer for June-Sept 2021 time period. The clinical trials claimed 94%, so there is a drop there. Nobody knows what will be the VE against sever infection a year from now, and we appear to have decided to preemptively boost so we might never know.
https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7037e2-H.pdf
https://www.pfizer.com/news/press-release/press-release-deta...
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Alas, none of this takes in account future virus variants and their interaction with OAS. OAS means that building an immune response against the virus today will prove ineffective for a virus variant 10 years down the line. The worst known scenario was encountered with dengue fever. An excerpt from a 2011 paper summarizing the dengue situation:
"Original antigenic sin has the advantage that a response can be rapidly mobilized from memory. However, the downside is that in some cases, such as dengue, the response is dominated by inferior-quality antibody. In influenza, original antigenic sin has been shown to reduce the effectiveness of vaccination (13, 34, 51). In dengue, the effect of original antigenic sin has considerable bearing on vaccine strategies. Once a response has been established, it is unlikely that repeat boosting will be able to change its scope, meaning that balanced responses against the four virus serotypes will need to be established with the first vaccine dose."
The clinical trials were run against the original version, while the data you presented seems to be overlapping with the spread of Delta, yet you never mention Delta in your comment.
Let's look at the weekly UK vaccine surveillance report, week 36 vs. week 42, afaik both within the UK Delta wave. For VE against severe disease, let's look at 'Deaths within 28 days of first positive COVID-19 test by date of death' tables. Let's pick age group 40-49 (older parents) and compute VE = 1 - vax_ratio / unvax_ratio.
week 36, VE = 1 - 0.4 / 3.1 = 87%
week 42, VE = 1 - 0.5 / 2.0 = 75%
FWIW, none of this makes me any happy. I wish the vaccines were holding effectiveness, that we didn't need a booster within 1 year of the initial shots and that the pandemic was over. Alas, reality does not cooperate.
https://assets.publishing.service.gov.uk/government/uploads/...
https://assets.publishing.service.gov.uk/government/uploads/...
> These data should be considered in the context of vaccination status of the population groups shown in the rest of this report. The vaccination status of cases, inpatients and deaths is not the most appropriate method to assess vaccine effectiveness and there is a high risk of misinterpretation. Vaccine effectiveness has been formally estimated from a number of different sources and is described earlier in this report.
In particular, the reduction of death rates among non vaccinated over time may be caused by natural selection, i.e. the weak died already while the remaining ones have unusually strong immune system (aka survivorship bias [2]).
There may be other unaccounted confounders, too, such as a change of behaviour over time where the degree of change is dependent on the age group and/or vaccination status. For example, an apparent reduction of effectiveness for younger people may be caused by them going back to work/study, thus increasing their probability of getting infected, while older folks staying in care homes as before.
Funnily enough, both Simpson's paradox and uncorrected confounders can result in observed correlations that are opposite to the real causality effect.
And to clarify, I'm not saying your VE numbers there are wrong, just warning readers about the dangers of statistics.
OTOH this is not an isolated data point. We have: the booster push (why?), the veteran study, the PHE data. Something doesn't add up. For whatever reasons, the observed epi VE, after all the confouding factors are accounted by reality, is fading for both infection and severe infection, though VE agains severe infection is fading at a slower rate. To the point of J&J VE against infection (the weakest of the bunch) being almost gone in 6 months. I don't have a time machine, but I'm really interested to see how the Jan 2022 VE numbers hold up across the board.
Given OAS concerns (please re-read the dengue study excerpt I already quoted), near zero covid risk for kids, rapidly fading VE against infection and the general lack of long term data about covid & immune system (no time machines), what exactly is the rush to vaccinate kids against the original variant?! And why do we pretend we can just tweak vaccines to any new variant, when, while technologically we can concoct any protein we like, the immune system doesn't turn on a dime?
> Despite the persistent connotation of “sin” as a negative attribute, it is clear that OAS-like responses are neither inherently “good” nor “bad.” The desirability of OAS responses is instead context dependent
It doesn't really seem from that article like we have the means to predict what OAS will be most beneficial in the future, so I think everyone are just flipping a coin here. Either you get OAS from some random vaccine available at some point in time, or you get it from randomly catching some random virus at some point in time.
Seems to me that one doesn’t pause when being attacked by a bear, a big cat, or even a wasp. And unless you’re anaphylactic, the latter can’t fudge you up as bad as a virus. Don’t pause too long, leopards are on the prowl.
My take of your entire thread is we let these natural processes kill millions because we fear a significantly smaller long term risk.
Side note: I hope we can do better than taking at face value investor press releases by the biopharma corps producing the vaccines.
You are correct that it isn't proving vaccine efficacy, but it is showing a different set of antibodies created by the variant vaccines that are more effective at neutralizing the targeted variant than the antibody collection created by the original, WT-targeted vaccine.
>Side note: I hope we can do better than taking at face value investor press releases by the biopharma corps producing the vaccines.
I hate science by press release too. I wish I was better at bookmarking the pre-prints and journal articles I find/read, but they'd just be a mess I couldn't find anything in either :|
Now, all the epi data we have indicates that the covid mRNA vaccines are effective against covid variants of concern. No need to panic.
"Original Antigenic Sin Response to RNA Viruses and Antiviral Immunity"
"Abstract: The human immune system has evolved to fight against foreign pathogens. It plays a central role in the body's defense mechanism. However, the immune memory geared to fight off a previously recognized pathogen, tends to remember an original form of the pathogen when a variant form subsequently invades. This has been termed 'original antigenic sin'. This adverse immunological effect can alter vaccine effectiveness and sometimes cause enhanced pathogenicity or additional inflammatory responses, according to the type of pathogen and the circumstances of infection. Here we aim to give a simplified conceptual understanding of virus infection and original antigenic sin by comparing and contrasting the two examples of recurring infections such as influenza and dengue viruses in humans."
I think the quick (and overly simplistic) answer to this question is that models (e.g. convolutional networks) that predict which chunks of viral (or human) proteins are displayed to immune cells (HLA presentation), along with other kinds of models (like those predicting crossreactivity of T cell receptors against mutated epitopes) are really primitive (mostly because of low quality training datasets, it's not really a hard problem like e.g. protein folding).
Hence, rushing a new vaccine is not easy as there is a lot of labwork to do. As a matter of fact, all COVID vaccine designs had essentially the same payload (the whole spike protein). Modern subunit vaccines would typically include only little chunks of the spike (to increase efficiency and avoid side effects). But this was not trivial to do quickly without good in silico models.
Or do a mix - first shot ancestral, second shot Delta.
* It's hard to recruit non-vaccinated participants
* There will be safety issues to address on people that have received multiple shots and / or designed against different strains
This may of course change with new variants.
This goes against the paper:
>A boost with mRNA-1273.351 appeared to be more effective at neutralization of the B.1.351 virus than a boost with mRNA-1273, evidenced by the higher mean GMT levels in the Part C cohort 1 participants (1400) than the GMT Part B participants (864) against the B.1.351 virus. Additionally, the difference between the wild-type and B.1.351 assays at day 1 dropped from 7.7-fold prior to the boost with mRNA-1273.351 to 2.6-fold at 15 days after the boost.
Thank you for posting this though -- I was looking for it earlier for my own comment and couldn't find it! Bookmarking now.
Novavax has also been working on a Beta variant booster (and I believe has moved on to a Delta booster that hasn't started NHP trials yet) -- here's some info from a presentation: https://www.novavax.com/sites/default/files/2021-05/NVAX-WVC... (It's slides 17 and 18)
Pfizer/BioNTech definitely has a Delta booster getting ready for NHP trials, but my Google Fu is lacking today, apparently.