Pfizer starting another Vaccine trial

Re:  Inoculating the world

Wiley Horne

Hi David,

“ if we want to stop the assault of variants, we need to (but who is "we") figure out how to get mRNA vaccines dispatched around the world‘

Certainly agree with you 100% on this.

Right now, India is ground zero. There’s a snag: Pfizer/BioNtech have been in negotiations for weeks—Modi govt will not indemnify the vaxx makers against lawsuits over complications. As US, UK, and EU have done.

https://fortune.com/2021/06/10/india-covid-vaccine-pfizer-indemnity-legal-lawsuit-protection/

Wiley

maddening....

David Weaver

I have a theory- that there's a lot more asymptomatic covid than we know, but that we get it from people who are mostly symptomatic.

Translation, if everyone has a viable vaccine in them (or nearly everyone) I don't think we would pass much of it to each other and this would go away much more quickly.

The only other route to that point is everyone getting actual covid (many before vaccinated), and that's a terrible way to get to the same point. There will be fewer around to talk about it.

But there's conflicting data for everything (including my asymptomatic theory - as in the group that studied the long term production of antibodies in bone marrow did not find evidence of covid infection in the folks who had two shots).

if ever there was a time for governments to waive liability or pass legislation for a one off waiver, I don't know of a better one.

(we had a short issue with this in PA even - the supply of vaccine was initially fine, but getting it distributed was slow. What was the hold up? The state claimed that they didn't have the legal ability to fund training people to distribute the vaccine and instead of making a big deal about it 24 hours a day, they sat on it "following the rule").

Re: An odd obsession...

Jesse Cloud

As Ellis would say, a couple of things...

1. I'm not a fan of Big Pharma, but that's from the crap they pulled with Oxycontin and currently the incredible pricing of insulin. If Pfizer makes a boatload of money through honest means then more power to them in my book.

2. There are two reasons for a booster either the antibodies disappear or a new variant that is resistant to the current vaccine develops. At this point, there is no evidence of either happening. That doesn't mean we shouldn't be vigilant and ready to move quickly when/if needed. With the low rate of vaccination in most of the world, its probably just a matter of time until a variant appears that is not vulnerable to the vaccine.

2+. The bottom line is that Covid is a new thing, there is still a lot we don't know. Until we do know, the fallback is to assume it works like the flu. Yes that was wrong about a lot of things but its what we have got. I think many epidemiologists envision something like the annual flu shot to address new variants and strands annually.

fundamentally different from the flu

Bill Tindall, E.Tn.

The flu virus looks like a stalk of broccoli. One part of this broccoli (flowers or stem can't remember which) mutates often. The flu vaccines target this part. So far a vaccine on the less mutating part has eluded development.

The Covid vaccines target some part of the virus that does not mutate as rapidly, or at all.

Re: What, specifically is incorrect?

TomD

"Nothing you've just said changes my opinion. I think you are assuming the worst of motivations based on whatever it is you are reading about this subject. Sure there is a kernel of truth in it, but nothing more."

Speaking of the worst of motivations, this is the company that's $2.3 billion settlement included a record-breaking $1.3 billion criminal fine.

Violations under the False Claims Act, including Off-label promotions, and kickbacks.

And all the first to market producers of vaccines have great big records.

I have a healthy level of skepticism on regulatory proceedings, so maybe they just got jammed up and paid up. In which case the regulators are crooks. Nice set of choices.

#2...

David Weaver

your number 2 is one of the data related things for me. I'm not knowledgeable about biology of pharmaceuticals, but...

...there was a big data mismatch between detection of antibodies and significant sickness recurring. The former was used as a scare story for a while "antibodies gone as soon as 6 weeks to 3 months!" with suppositions of doom of getting covid over and over.

The reality is that in the longer term, antibodies are produced in marrow (from what I've read) and more exposures (through mrna vaccine or sickness or both - the supposition right now is exposure to both is better than exposure to either or) make for more accuracy, with one story suggesting that accuracy of the response may not be that great for people who had severe covid (compared to individuals who had milder cases).

My point with this being the lack of antibodies is trotted out for a scare story, but the data of lack of serious sickness on any regular basis (for healthy individuals recovered from covid) isn't talked about much. One of them is a real measurable outcome, the other is measurement to try to predict an outcome. The next question (a reasonable one, I think) is whether or not asymptomatic and mild cases (that never progress) really transmit much or any. It seems unlikely that they do because there's also data showing suggestion that mild and asymptomatic cases aren't reported (and presumably, the cohort of folks around those second or breakthrough cases aren't getting ill - that would make a lovely news story "vaccinated person gets mild sickness, ignores it and kills family").

I'm watching the CDC case data now that delta is prominent to see what happens. I wish it was easy to see what happens in real time with two-dose vaccine recipients vs. unvaccinated individuals (it seems inevitable that there will be an increase in cases among those folks).

Vaxx versus unvaxx—deaths

Wiley Horne

Hi David,

Numerous current news stories reporting about all Covid deaths these days are among the unvaxxed. Example from Medscape, which avoids sensational headlines and verbiage:

https://www.medscape.com/viewarticle/953957

Wiley

Sure...

John in NM

Look into any company and you will find some dishonesty. In big companies the temptations are bigger, the mistakes to be covered up are bigger, and the likelihood of their getting caught will be bigger. The bigger it is, the more it will drive clicks and sell ads, so the news rushes to breathlessly report on it.

None of that bothers me much. Corporations, governments, anything involving people will be imperfect. I don't see why their failures negate the successes in the minds of some. That is irrational and I think rather counter productive.

So to me, a judgement or two against Pfizer doesn't really take much away from the achievement of getting this new type of vaccine out into the population in record time - and that is not to say they were the only ones to work at that, they are just the ones under discussion here. The other companies involved and the competing companies deserve as much credit, or in cases like Emergent, they deserve blame.

yes...

David Weaver

..that leads to a more nuanced discussion then for everything else.

Without going back and looking at the CDC results, I believe there were 865 deaths or something of vaccinated individuals.

I called that close to none (which I hope nobody finds offensive). In reality, the prevalence of covid and the fact that the trials stated that the incidence of covid with vaccine would still be 5% or more (depending on which version), folks are going to show up morbid or mortally ill and become deceased and then pop a positive covid test.

What's vexing in the data is how few *other* positive cases there were reported among asymptomatic and mild. They *must* be out there as the follow-up data suggests that the first thing to go is prevention of covid in general, with little increase in hospitalization and nearly no deaths. I'm sure there are some compromised folks in that 865 cohort who actually did die of covid, but many probably died and just had covid at the same time (a greater proportion than the excess deaths over the last year and a half).

I'm heartened to see that the hospitalization rate in the israeli data has slipped only to 93% (despite the statement that protection from all cases has dropped much more). I suspect a lot of things - as mentioned above. I suspect that it's safe for someone with two vaccine shots to get covid and go that route and eagerly await data over time to find out if they're really responsible for much transmission in the long run.

I suspect that my under 12 kids would be better off getting covid now than waiting, and they may be better off getting it than getting a vaccine (toss up) - no guarantee that future variants don't become more harmful to kids. Seems unlikely, but what's guaranteed.

And it seems to me the absolute biggest problem to solve is how to get better vaccines used around the world - partially a production and logistics issue, and much of a politics and pride one. With deadly consequences.

Re: yes...

AlanWS

Conclusions depend on data you believe to be reliable. The data I believe are summarized here.

The Delta variant changes a lot. In Australia its spread is easy to follow since it's all derived from one case. One guy went to a party, and every one of the 27 unvaccinated attendees got it including children, and none of the vaccinated ones. That is much more infectious than other variants. https://www.nytimes.com/2021/07/02/world/australia/delta-covid-zero.html There is spread documented on camera between two people who simply walked by one another. This is now the prevalent variant most places.

Problems persist in even asymptomatic cases for a long time: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781687

The vaccines are incredibly effective and very safe. They provide better protection against disease than having had it, and a booster is a good idea for those who have. Trials were quick, but involved as many people as usual (or more). When problems do arise with vaccines, they tend to be early, but that's not true of disease. Monitoring of millions of people vaccinated after the trials has been more thorough than usual and has not found significant problems at levels above baseline.

There are many scientists and organizations evaluating vaccine safety that have concluded it is very safe. In contrast, the reports of serious problems seem to all originate from a very small number of people. https://www.sciencealert.com/most-anti-vaccine-conspiracies-online-come-from-the-same-12-people-study-shows

But the major argument for widespread vaccination is that it's the reservoir of virus, almost exclusively in unvaccinated people, that leads to new and potentially more dangerous variants. The more people infected, the more quickly variants will arise.

Before Delta, one dose of vaccine was quite effective at prevention, but two better. With Delta, two are needed. Having had the disease protects about as well as one vaccine dose: i.e. not well against Delta. We don't want a variant to arise that is more infectious and/or dangerous than Delta. The more people infected, the more likely that is.

Thank you

Johanna Johanson

Thank you, Bill, for volunteering to test a vaccine. We are all in your debt.

Re: yes...

Johanna Johanson

You are right on about the unvaccinated being a reservoir of disease. I don't think many people understand that concept.

It was an easy choice

Bill Tindall, E.Tn.

I researched what was known about the vaccine from what was published on the Phase 1 trial. There were no adverse effects in the Phase 1 trail and zero viral reproduction in vaccinated subjects. Effective and safe based on the data.

The vaccine was developed in Germany, a favorable location for sound science. Results looked good enough to Pfizer that they were willing to back it with a billion dollars for development. The benefit of early access to vaccine far outweighed what I considered no risk. Several of my former coworkers that are chemists also signed up when my wife and I did.

Re: yes...

TomD

Before the back slapping gets out of hand, remember when Fauci said you will be vaccinated, but you will need to wear masks and socially distance, he wasn't wrong. Vaccinated people that are out there, flip off variants during a pandemic. Even though vaccinated you will not be 100% covered but you won't get sick enough for hospitalization, for the most part. That is you hosting the disease, mutations occurring, and you possibly infecting others. For some people, they are providing this useful service just so they can go shopping etc...

The UK is seeing a steep rise in infections among vaccinated people, so called breakthrough cases. The US is dealing with the phenomenon, I gather, by not collecting the data, unless a breakthrough case results in hospitalization, or death.

Unvaccinated people who are at risk but safe (poor potential health outcomes, but good strategy) are not going to be getting sick, and they won't be acting as though the all clear has sounded and there is no problem.

The key issue remains whether you are at risk. Most people will benefit from a vaccine, but not everyone does. Even for pro vaccine people there much be someone manning a weather station 1000 miles from civilization who is not dogging their responsibility to humanity by jumping ahead in the line for vaccination. I remember at one time there was a nice little line in white privileged shamming for such people, or even countries.

I spent a charming 4 months in New Brunswick last year where there were basically zero cases. They have never reached community spread, and vaccinations are selling like hotcakes. They will possibly successfully avoid the pandemic altogether. While there, we as usual stayed on out acreage, and saw no one. My apologies for putting humanity at risk.

Re: Booster info

TomD

Pfizer announced it will be asking US and European regulators within weeks to authorize a booster dose (shot #3) of its COVID-19 vaccine ( https://globalnews.ca/news/8014256/pfizer-booster-covid-delta-variant/ ). Pfizer says the booster targets the full spike protein of the Delta variant to provide even better protection against variants that have started to partially evade the immune system.

Pfizer predicts people will require a vaccine booster 6-12 months after being fully vaccinated (2 doses) based on unreleased data from a booster study they have been working on which they claim raises antibody levels 5-10 times higher than 2 doses. Within hours the CDC, FDA, and NIH in the USA issued statements that American who have been fully vaccinated do not need a booster shot at this time and are engaged in science-based rigorous process to consider whether or when a booster might be necessary ( https://www.washingtonpost.com/health/2021/07/09/pfizer-booster-shots-hhs/ ).

Pfizer said it is seeing waning antibody levels in people after 6 months ( https://www.wsj.com/articles/pfizer-to-ask-regulators-to-authorize-covid-19-vaccine-booster-11625784072?mod=djemalertNEWS ). It is expected that antibody levels decrease over time and how the immune system normally works as there is no need for the body to keep high levels of antibodies long-term for a pathogen it has not seen in some time. Antibody levels are easy to measure but the immune system also has memory B and T cells which are trained to identify the virus and can generate additional antibodies and defences against the virus if the person becomes exposed again. Further research will need to be completed to determine if 2 doses of the COVID-19 vaccines are still effective after 6 months and a year when the immune system engages its other components such as memory cells which create more antibodies as needed to fight off the virus.

Now that the USA is pushing back it seems that Pfizer will be meeting with US officials (Fauci, NIAID, NIH, CDC, FDA) to show its data that immunity against the coronavirus declines in vaccinated people over time, particularly in the elderly ( https://www.washingtonpost.com/health/2021/07/10/covid-booster-shot-pfizer/ ). Apparently Pfizer gave a similar briefing to the Europeans last week.

(I get daily updates, but i don't know if I am to credit the source or not, I think he just has a private distribution list)

Re: Booster info

TomD

Sorry, I somehow didn't paste all of that:

U.K.'s Joint Committee on Vaccination and Immunisation (JCVI) has already issued guidance on starting a booster shot campaign, potentially in about 2 months ( https://www.cbc.ca/news/health/covid-19-third-dose-booster-shots-1.6092834 ). The advice is that a third vaccine dose should be offered to the most vulnerable starting in September 2021 including those who are immunosuppressed, living in long-term care or retirement homes, people aged 70 years and older, and front-line health workers.

Dr. Allison McGeer, an infectious disease specialist at Mount Sinai Hospital in Toronto said "People who live in long-term care facilities, people who are immunocompromised, do generate lower antibody levels and they decline faster over time. There are likely to be some of those people who will not be well-protected come October or November and who might be better protected if they get an extra dose of vaccine."

The WHO on the other hand is slamming the talk of booster shots when policymakers need to look at the broader picture when they're considering whether to offer booster shots — including the fact that many people in the world have not yet been able to get even their first dose of a COVID vaccine. Dr. Tedros Adhanom Ghebreyesus, WHO's director general, said, "Vaccine nationalism, where a handful of nations have taken the lion's share, is morally indefensible and an ineffective public health strategy against a respiratory virus that is mutating quickly and becoming increasingly effective at moving from human-to-human."

Canada's National Advisory Committee on Immunization (NACI) is watching the scientific data develop as they consider whether booster shots will be needed — or when, said Anna Maddison, spokesperson for the Public Health Agency of Canada.

Re: Vaxx versus unvaxx—deaths

TomD

This data seems to have been pretty unreliable from the beginning. Dying with COVID, vs dying of COVID. Another example being the PCR cycles stuff. I don't get why people who have severe medical and exposure risks are not getting vaccinated, but since it is pretty easy to avoid getting COVID if you can manage your life, I don't get all the panic from the vaccine pro folks either.

I was in financial regulation during my working life, and pandemics share a similar hardship, and probably security also. One of your most important tools is the career lie. In a crash, some schmuck is going to have to go out there, a figure who always told the truth, and lie. Then he will need to resign. It is just the drill. And when you see some guy fall on a sword like that, you sure hope someone doesn't take their deposits out of the bank.

Curious ...

David Weaver

are we going to see people who had mild and moderate covid (what I understand is that folks who had severe covid may not have as accurate of antibodies) getting moderate covid on a regular basis with delta.

If not, perhaps if they have mild and asymptomatic, do we have much data suggesting they'll actually spread anything.

I am speaking not from the standpoint of single covid or single shot, I'm speaking from the standpoint of two pfizer or moderna shots, because we're talking about a third. Do we have information or good data showing that people who have two shots are actually better off than people who had a third (and that's a hard question to answer because it's two pronged:

* if more get delta, are they better off getting delta or getting a third shot (this is from their personal standpoint)

* if they are *not* better off getting a third shot vs. getting mild or asymptomatic delta, can they spread delta, or rather not "can they spread it" but are they actually spreading it. We are hopefully looking at outcomes and not possibilities

The covid and no shots is a curiosity to me, but it's meaningless on a personal level because I've had two shots and no covid (that i'm aware of). It's my opinion (and I'm not a medical professional) that anyone who hasn't had covid should have two shots. I'm waiting for the actual data about superiority of two shots over someone who has had covid before getting it a second time (I don't think we'll get good data on that - outcomes, I mean) because if covid + 1 shot or covid alone has the same outcome as two pfizer/moderna with the delta variant (chance of getting mild to moderate cases - severe is relatively uncommon in both cohorts, I'd bet), the CDC would seemingly drag their feet in confirming that.

And that doesn't even touch on the fact that the data for the cohorts in general is incomplete, and estimating how and in which direction is a bit of a crapshoot.

Skepticism of the third shot before there's a good reason to get it data-wise in my case isn't skepticism about the mrna vaccines. I got two shots as soon as I could - literally within days of being allowed (that's as soon as I could schedule). If you asked what the most valuable thing to me has been in the last decade (aside from the birth of one of my children), I'd say getting two pfizer shots.

So, I wasn't wrong here, was I?

David Weaver

Pfizer is looking for authorization before having outcomes data -seems a bit premature given the fact that here where I am, we are 62% double shot vaccinated (18+) and well over 80% one shot or more (without considering that some of the no-shot and one-shot cohort has had covid).

What's that translate to? Delta is the dominant variant here. Our total case rates have dropped the last several weeks, as have the positive testing rates (so it's not likely from a lack of testing).

The outcome is that covid is dropping despite delta, the push is the hope to get authorized to provide a third shot, anyway.

I'm sure that some on here would say that my cynicism was inaccurate earlier. It looks to have been right on the mark.

(it is not a surprise that elsewhere in the US where vaccination rates are lower, there is a slight weekly increase in cases - this isn't an issue of three shots vs. two, though. I shouldn't have to explain further at this point).

By the way...

David Weaver

..I'm glad to see that the CDC and NIH pushed back instantly. Ignoring outcomes so far and basing the recommendation on waning antibodies is like stepping back in time almost 18 months. It's not suprising that pfizer would do it (refer back to their statement about hoping to create a durable revenue stream).

Why is pfizer focusing on antibodies and not actual covid outcomes? If a lower level of antibodies (the long term marrow production referred to elsewhere) provides adequate protection, are we actually better off trying to maintain a "I was just sick" level of antibodies?

There's a missing scenario here...

David Weaver

..covid plus one dose appears to be more effective than no covid and two doses.

https://www.nature.com/articles/d41586-021-01609-4

All of the scenarios should be provided. That's important in context along with the data showing that two vaccine doses are better than having had covid.

For folks who did have covid and who have practitioners insisting that they get two more shots, I wonder what the side effects are like. I know only one person who had that scenario. He got the first shot, got covid in less than a week (Before being protected) and the second shot was given to him two weeks later. I expect that something may have changed since then as his reaction to the second shot was severe.

My prior comment still stands in the context of this thread though, with the original question -where is the data suggesting that as a society, we need a third shot? In PA where I am, the delta variant dominates and case rates continue to drop. I suspect it's only the unvaccinated who will be significantly increasing case numbers, with folks with one shot contributing a little.

Perhaps... but a couple points to consider...

John in NM

First, Pfizer is seeking authorization for a booster - not necessarily the same thing as seeking a recommendation for it. I would guess (and in a completely uneducated way) that this means they would be that much further ahead IF a booster is proven to be beneficial based on study data.

As a corollary to that point, recall that these vaccines are under emergency use authorization, NOT approval from the FDA. Speed is of the essence in this case, I could see them wanting to have booster authorization before completing the studies.

Second point, Pfizer has, without a doubt, noted the public's expectation regarding vaccination, egged on by the click baiting news media. Declining efficacy in the prevention of mild cases is NOT part of the general public's expectation. You and I know that this expectation is foolish, but then we read and exercise some skepticism.

For what its worth, my second dose was right around six months ago. I'll let you know if I catch it. I think you are right in supposing that a mild case following vaccination would be as good or better than a booster.

Dr. Fauci agrees with you, David!

Wiley Horne

https://www.cnn.com/2021/07/11/politics/fauci-booster-shots-sotu-cnntv/index.html

Incidentally, you don’t have to be cynical to judge that a profit-making corporation is trying to make a profit. But a PR effort is the only leverage they have—the scientists will judge the data and make the recommendations. Which is what you see happening with the pushback against Pfizer’s press releases.

Have you been speaking to Dr. Fauci ?

Wiley

I'm totally open to the a case for myself..

David Weaver

..I know I've said that half a dozen times, but it sounds like a good way to go building for the future and perhaps one that doesn't involve constantly getting a booster (and potentially increasing side effects). It would seem they should study a booster with lower and lower dose contents because it should take less to induce a robust response.

I have some (not much - I don't live fearing what will make me ill or kill me most of the time) concern that perhaps introducing more and more material to get a response may not be a great idea (increasing sensitivity and perhaps complications), but I'll be glad to let the test pools find that out.

Re: Dr. Fauci agrees with you, David!

David Weaver

Nosir! I watch the outcomes data. Ultimately, that's the most reliable data - as we battered earlier in this thread, it became popular to fret about the near-post illness high-antibody count because that made a good story "antibodies fade quickly- are we destined to battle covid over and over?" (given the early illness, that seemed like potentially a very bad thing - something that has a 5 tenths of a percent fatality rate over and over?

The only thing missing was people getting sick, and not just mildly sick, but seriously sick. I want to see the problem defined before seeing a solution (on a widespread basis).

Australia and others (Japan, etc - and much more) have a real problem - low vaccination percentages - they need their two shots (based on the data) far more than we need a third, but Americans are a pretty reliable source for health care revenue - and profitable health care revenue.

The flip side is if I were in the finance group at Prizer, I'd be the proverbial man with a hammer.

(and that aside, I'm glad to see fauci's quick response).