Coronavirus: Vaccines

[RTH10260]

Pfizer vaccine provides 90 percent protection against hospitalization for six months, study finds.

The Pfizer-BioNTech coronavirus vaccine is 90 percent effective at preventing hospitalization for up to six months, with no signs of waning during that time period, according to a large new U.S. study conducted by researchers at Pfizer and Kaiser Permanente.

The vaccine also provides powerful protection against the highly contagious Delta variant, the scientists found. In a subset of people who had samples of their virus sequenced, the vaccine was 93 percent effective against hospitalization from Delta, compared with 95 percent against hospitalization from other variants.

“Protection against hospitalization remains high over time, even when Delta predominates,” said Sara Tartof, an epidemiologist at Kaiser Permanente Southern California and the first author of the study.

The vaccine’s effectiveness against infection did decline over time, however, falling from 88 percent during the first month after vaccination to 47 percent after five months.



https://www.nytimes.com/live/2021/10/04 ... tion-study

[AndyinPA]

https://www.nytimes.com/2021/10/07/us/p ... -5-11.html

WASHINGTON — Pfizer and BioNTech said on Thursday morning that they had asked federal regulators to authorize emergency use of their coronavirus vaccine for children ages 5 to 11, a move that could help protect more than 28 million people in the United States. The companies have said they were submitting data supporting the change to the Food and Drug Administration. The agency has promised to move quickly on the request and has tentatively scheduled a meeting on Oct. 26 to consider it. A ruling is expected between Halloween and Thanksgiving.

Parents across the United States are anxiously awaiting the regulators’ decision, which could affect family life and the operation of schools. Clearance depends not only on the strength of the clinical trial data, but on whether they can prove to regulators that they are able to properly manufacture a new pediatric formulation. Dr. Janet Woodcock, the acting F.D.A. commissioner, said last week that children might require “a different dosage or formulation from that used in an older pediatric population or adults.” Pfizer has proposed giving children one-third of the adult dosage. That might require adding more diluent to each injection or using a different vial or syringe.

The company was expected to describe the method it intended to use in its submission to the Food and Drug Administration. Regulators will have to examine the purity and stability of mass-manufactured doses of the vaccine and determine that it matches the quality and potency of doses given to children in clinical trials. A pediatric dose will also most likely require new labeling, with special codes that would allow the Centers for Disease Control and Prevention to track specific lots in case of reports of serious side effects.

Children rarely become severely ill from Covid-19, but the Delta variant drove nearly 30,000 of them to hospitals in August. According to the American Academy of Pediatrics, nearly 5.9 million Americans younger than 18 have been infected with the coronavirus. Of the roughly 500 Americans under 18 who have died, about 125 were children ages 5 to 11.

[Sam the Centipede]

https://www.nytimes.com/2021/10/07/us/p ... -5-11.html

Pfizer has proposed giving children one-third of the adult dosage. That might require adding more diluent to each injection or using a different vial or syringe.

[/quote]
That's good to hear: small children's high performance immune systems don't need as much provocation to respond as for us larger and older folk.

Whether healthy children that young should be vaccinated is a separate question, involving epidemiological, ethical and public health issues.

[raison de arizona]

Whether healthy children that young should be vaccinated is a separate question, involving epidemiological, ethical and public health issues.

They should. Glad I could clear that up for you.

[Sam the Centipede]

Whether healthy children that young should be vaccinated is a separate question, involving epidemiological, ethical and public health issues.

They should. Glad I could clear that up for you.

And you base that assertion on what information? Regulatory authorities differ from your view. For example, as I recall, the UK's vaccine committee said that it was not clear that healthy teenagers should be vaccinated because the risks and benefits to them were approximately equal. The decision to offer vaccination to healthy teens (by a different agency) was taken not on physical health grounds but because disruption to their lives (schools closing, periods of isolation, etc.) was causing the kids to suffer mentally and educationally.

So how did you reach your conclusion?

[raison de arizona]

Whether healthy children that young should be vaccinated is a separate question, involving epidemiological, ethical and public health issues.

They should. Glad I could clear that up for you.

And you base that assertion on what information? Regulatory authorities differ from your view. For example, as I recall, the UK's vaccine committee said that it was not clear that healthy teenagers should be vaccinated because the risks and benefits to them were approximately equal. The decision to offer vaccination to healthy teens (by a different agency) was taken not on physical health grounds but because disruption to their lives (schools closing, periods of isolation, etc.) was causing the kids to suffer mentally and educationally.

So how did you reach your conclusion?

#1 I wasn't talking about teenagers, 12 and over can already get the vax and are recommended to. I don't know about recommendations in the UK though.
#2 The sources I read (in a nutshell) said that children, while tending to be asymptomatic or at least lesser affected in most cases, are often carriers. For instance, Tommy goes to school with five hundred other kids, there is an outbreak and say forty direct people get it (not a number pulled out of my butt, just numbers recollected from my kid's school last year.) They bring it home to their loved ones, their parents, their siblings, their grandparents, who are at risk. People end up in the hospital, people die.
#3 Personally, my kid 9yo is ready to get it now last year ago. His 12yo cousin literally got it on his birthday. I'm immune compromised X 2 diseases and immune suppressant medication. My kid does really bad at remote school, he has difficulty learning that way, and has difficulty without the social aspect of school. Still, he is deathly afraid of bringing home covid to me, because he knows it could hit me hard (even thrice vaccinated am I). He can't wait to get his vax. I can't wait for him to get his vax. His school has already had FOUR outbreaks this year. And many more scares. Anything that can help put covid in the rear view mirror (as much as possible) is something I'm going to get behind.

I get there are differing opinions on this. I agree with the ones that promote getting kids vaxxed and haven't seen anything that has changed my mind.

[Sequoia32]

So how did you reach your conclusion?

I reached mine based on the probability of another variant that massively impacts children.

[Sam the Centipede]

Thanks (both!), yes, those are good reasons, and if I had kids of that age, I'd have no objection to them having a vaccine. But the reasoning of public health authorities has to be significantly different. It is different for a parent and a child to freely agree to the vaccine, than for a government to mandate or heavily promote it; it's rather like that idea in law (as stated by Benjamin Franklin) "it is better 100 guilty Persons should escape than that one innocent Person should suffer" - the negative outcomes are weighted more heavily than the positive outcomes.

The probability of a new variant arising that disproportionately impacts kids is surely very small. What could the mechanism for that possibly be?

The flu season is going to be interesting. Kids are often asymptomatic transmitters of flu, but they and adults haven't been exposed to various flu viruses much for a year or more, so immunity in kids and adults are both low. Against that, flu vaccination levels will probably be high in many countries.

[Sam the Centipede]

This morning I listened to Prof. Sarah Gilbert of Oxford University being interviewed by Prof. Vincent Raccaniello of Columbia University. Prof. Gilbert led the development of the Oxford/AstraZeneca ChAdOx1 nCoV-19 vaccine. She speaks very well, but most of the story she related is well known. Anyway, here are some highlights.

I was driving as I was listening, so I was occasionally distracted and my memory is faulty on details.

The Oxford team started work in January 2020, as soon as they receive the genetic sequence data from China. They repurposed the platform and science they had developed for vaccines for SARS and MERS, both caused by coronaviruses similar to SARS-CoV-2. Both SARS and MERS caused real fear that they might initiate pandemics, but ultimately the diseases and hence the impetus for vaccines fizzled out. MERS occasionally breaks out, and is serious in humans, but its reservoir is in camels, which is where the humans catch it (very little transmission from person to person). In camels the MERS virus just causes a runny nose and a bit of a cough, so there is little incentive for camel owners to vaccinate, even though there is a vaccine.

The rapid development of the Oxford vaccine was, as we know, not due to cutting corners (as some anti-vaxxers claim) but for two reasons: (1) because the science and the adenovirus vector technology was directly transferable from the work on SARS and MERS, and (2) the usual delays due to writing up and reviewing each phase, then proposing and seeking permission and funding for the next phase before setting it up were removed, as each phase was initiated as soon as the science was in place and verified. And the team's other projects were put on ice.

Prof. Gilbert seemed understandably proud of the fact that 1.1 billion doses of the Oxford vaccine have been administered. That's well over half a billion people, definitely a huge impact for a small group's work. The Oxford vaccine is now manufactured in 25 different facilities in widely spread countries, with the Serum Institute in India being the largest producer. Asked if she wanted more production sites to open, Prof. Gilbert was noncommittal but said that each site was becoming more productive as it gained experience, and the real omission was the lack of vaccine production in Africa, which, as always, is the world's poor relation in health matters.

Asked about why the Oxford vaccine is two-dose, Prof. Gilbert's answer was a little vague (or I just didn't hear it clearly), and might have been that it was a prudent approach when they couldn't be sure that one dose would be sufficient. As is well known, all the two-dose vaccines give a good level of protection after the first dose, in fact significantly above the level that the WHO said in early 2020 would be the minimum acceptable for a viable vaccine. On the delay between doses, she said 12 weeks seemed ideal, but the UK had settled on 8 weeks largely because they were worried about the more transmissable Delta variant, so wanted to speed things up. (Remember how people were going "waah! I want my second dose after 2 weeks!", no, that's understandable, but waiting is better long term.)

On adjusting for variants, she said that could be done, but currently there didn't seem to be any need, and she thinks it's good that all production sites around the world (for this vaccine) produce exactly the same product.

I'm sure she said more, but that's probably enough. This is all from memory, so please feel free to identify errors.

Off Topic

Prof. Gilbert briefly touched on malaria, and a vaccine development project they had at Oxford. I think there is some news this week about malaria vaccines, but I haven't read it, and I'm not referring to that. This is just something interesting.

Malaria is called by a parasite called Plasmodium, which is a unicellular eukaryote, a relatively complex organism with a complex life cycle, very very very unlike a virus. When an infected mosquito bites a human victim to feed on blood, it transfers some Plasmodium into the victim's bloodstream. Within minutes the Plasmodium migrates to the liver and enters liver cells. Antibodies (the proteins circulating in the bloodstream) cannot respond to pathogens which are inside cells, only those circulating in the blood or outside cells. So a vaccine that only promotes the creation of antibodies is not going to be very effective. Instead, a vaccine needs to enhance T-cell response, because T-cells can detect infected cells and kill them, or cause them to be killed.

That's not relevant to Covid research, but it's an illustration of how much complexity there is in these issues.

[tek]

I'd like to point out here that 'asymptomatic' does not necessarily mean 'unaffected' ...

Adults are showing long-term damage from COVID infections even if they were asymptomatic, so it would be prudent to assume that children very well might also.

Also, as pointed out above, asymptomatic children can be very effective at spreading the virus.

So there are more "negatives" to worry about than just bad effects from the vaccines themselves.

[Sequoia32]

There is new insight on the COVID-19 vaccine and how it can impact your body.

As with most vaccines, it triggers an immune response, so your body is better prepared to fight if you are exposed to the virus.

That is causing some people to notice enlarged lymph nodes that linger, sometimes months after.

The doctor who spoke with sister station WBAL said she doesn't want this to lead to hesitancy or fear about the vaccine or mammograms — it is about having the knowledge about what to possibly expect.

https://www.kcra.com/article/persistent ... s/37897449

[Sam the Centipede]

I'm baffled by the choice of words in the quoted article:

As with most vaccines, it triggers an immune response, so your body is better prepared to fight if you are exposed to the virus.

Don't all vaccines trigger an immune response? If one isn't designed to do so, then surely it's not a vaccine??

Or am I missing something?

[AndyinPA]

https://www.reuters.com/business/health ... 021-10-12/

Oct 12 (Reuters) - Scientists at the U.S. Food and Drug Administration said on Tuesday that Moderna Inc (MRNA.O) had not met all of the agency's criteria to support use of booster doses of its COVID-19 vaccine, possibly because the efficacy of the shot's first two doses has remained strong.

FDA staff said in documents that data for Moderna's vaccine showed that a booster does increase protective antibodies, but the difference in antibody levels before and after the shot was not wide enough, particularly in those whose levels had remained high.

The documents were released ahead of a meeting later this week of the FDA's outside expert advisers to discuss booster doses of the vaccine.

[RTH10260]

news item w/o link (sorry rikker):

The booster shot with Moderna vaccine should be possible with half the standard dosis.

(maybe that's the issue with the FDA as above)

[AndyinPA]

news item w/o link (sorry rikker):

The booster shot with Moderna vaccine should be possible with half the standard dosis.

(maybe that's the issue with the FDA as above)

I had also heard that a half dose was what they were looking for. I had the Moderna. I'd like to see them make some kind of formal announcement.

[Notaperson]

Very interesting article about the benefits of a booster among Israelis. Note that it is based on a study not yet peer reviewed though.

How Triple-Jabbed Israel Is Exposing America’s Booster Shot Blunders

Millions of Israelis rushed to pharmacies and clinics for their third dose of COVID vaccine after the country’s health regulators authorized boosters back in July, and the apparent result—four months on—is striking.

For the roughly 4 million Israelis who’ve gotten boosted—that’s two-thirds of the adult population—COVID cases seem to have plummeted. A third dose of Pfizer’s messenger-RNA vaccine has reduced infections tenfold, according to the preprint of a new study that appeared online on Oct. 7. The study is not yet peer-reviewed.

Widespread boosting kicked COVID’s ass in Israel, according to the October study. The study’s Israeli authors scrutinized government data from July to October, comparing COVID infection rates in the boosted population against rates in the non-boosted population.

The numbers speak for themselves. “Confirmed infection rates were ~10-fold lower in the booster versus non-booster group,” the authors wrote. The benefit was even greater for older Israels. Infections dropped by a factor of 19 for people over 60, and by a factor of 22 for the 40-60 age group.

https://www.thedailybeast.com/how-tripl ... t-blunders

Link to the preprint of the study discussed: https://www.medrxiv.org/content/10.1101 ... 626v1.full

[AndyinPA]

https://www.nytimes.com/2021/10/14/us/m ... s-fda.html

A key advisory committee to the Food and Drug Administration voted on Thursday to recommend a booster shot of the Moderna coronavirus vaccine for many of the vaccine’s recipients, at least six months after a second dose. The panel endorsed a half-dose as a third injection for people 65 and older as well as younger adults at high risk because of their medical conditions or jobs, the same groups of people who became eligible for a Pfizer-BioNTech booster last month.

While regulators are not obligated to follow the panel’s recommendations, they typically do. Committee members said that while they hoped for far more robust data, a number of them said that F.D.A. had already sent a precedent by authorizing booster shots on an emergency basis for many recipients of the Pfizer-BioNTech vaccine. The panel voted after hearing from Moderna officials, agency scientists and a top public health official from Israel, which began offering boosters to Pfizer recipients two and a half months ago.

Dr. Eric Rubin, an adjunct professor of immunology and infectious diseases at the Harvard T. H. Chan School of Public Health, questioned whether Moderna has enough data showing whether a booster shot will create adverse side effects. Like Pfizer, “Moderna is presenting the results of a relatively small trial,” he said. But “Pfizer had all those real-world data from Israel” on its booster campaign, showing results from “millions of people who received the vaccine,” he said.

[Uninformed]

“Positive trial results for Valneva Covid vaccine”:
https://www.bbc.co.uk/news/health-58952473

“The Valneva Covid vaccine that the UK cancelled a 100m dose order for last month, works well at priming the immune system to fight coronavirus, phase three trial results suggest.
Blood results from volunteers who received the jab had high levels of neutralising antibodies against the pandemic virus.
It outperformed the AstraZeneca vaccine on this measure in head-to-head tests.
Valneva is seeking regulatory approval for its jab, manufactured in Scotland.
It is an inactivated whole virus vaccine, meaning it contains a dead version of coronavirus that cannot cause disease. This is the same way that flu and polio vaccines are made.”

[W. Kevin Vicklund]

“Positive trial results for Valneva Covid vaccine”:
https://www.bbc.co.uk/news/health-58952473

“The Valneva Covid vaccine that the UK cancelled a 100m dose order for last month, works well at priming the immune system to fight coronavirus, phase three trial results suggest.
Blood results from volunteers who received the jab had high levels of neutralising antibodies against the pandemic virus.
It outperformed the AstraZeneca vaccine on this measure in head-to-head tests.
Valneva is seeking regulatory approval for its jab, manufactured in Scotland.
It is an inactivated whole virus vaccine, meaning it contains a dead version of coronavirus that cannot cause disease. This is the same way that flu and polio vaccines are made.”

Interesting. I wonder how they're stabilising the spike protein to avoid ADE?

[Sam the Centipede]

Interesting. I wonder how they're stabilising the spike protein to avoid ADE?

Valneva claim to chemically stabilize spike but I don't know how. The generally similar Sinopharm and Sinovac inactivated virus vaccines don't explicitly stabilize spike, do they? All 3 vaccines use beta-propiolactone (BPL) as the inactivating agent, which can (with other manufacturing stages) affect the spike protein, and reports say that electron microscopy shows a mixture of pre- and post-fusion configurations in the Sino- vaccines.

Perhaps the fact that those two Sino- vaccines included a significant fraction of post-fusion spike suggests that ADE due to pre-/post-fusion issues is unlikely? Of course, having predominantly pre-fusion spike is desirable because that's what we want antibodies to, not the post-fusion configuration when the virus has already started its dirty work. It has been suggested that the relatively low efficacy (but still very good in absolute terms!) reported might have been due to the shortage of pre-fusion spike.

I'm not convinced by the idea touted that Valneva might be inherently more variant-proof due to raising antibodies and memory cells against M, N, etc. proteins as well as S. The focus on S in the mRNA and vector vaccines was because its structure is highly conserved, especially in the receptor binding domain, the others can vary more freely, potentially escaping existing antibodies. That said, variety is always good in immune responses!

The virus supply for the vaccines are grown in cell cultures, so the clever trick that the vector and mRNA manufacturers use of modifying the S gene to insert extra prolines (or perhaps other amino acids) into the spike protein to dissuade it from reconfiguring probably isn't an option, as it would block the virus's ability to grow in culture. Shame that.

[AndyinPA]

https://www.nytimes.com/2021/10/18/us/p ... sters.html

WASHINGTON — The Food and Drug Administration is planning to allow Americans to receive a different Covid-19 vaccine as a booster than the one they initially received, a move that could reduce the appeal of the Johnson & Johnson vaccine and provide flexibility to doctors and other vaccinators.

The government would not recommend one shot over another, and it might note that using the same vaccine as a booster when possible is preferable, people familiar with the agency’s planning said. But vaccine providers could use their discretion to offer a different brand, a freedom that state health officials have been requesting for weeks.

[keith]

I was 'discussing' on another forum the other day about vaccine efficacy.

The guy was saying that Polio and Smallpox vaccines were just about as perfect as a vaccine could be, the Covid vaccines are worthless in comparison.

The Polio and Smallpox vaccines are 95% effective. (Smallpox is no longer available due to no virus in circulation anywhere )

So I looked up the article I read a year or so ago that compared the efficacy of the five vaccines that were then available. The four 'double dose' vaccines were 88% to 90% effective at preventing severe disease requiring hospitalization, and approached 100% at preventing death.

The odd one out was Johnson and Johnson. It is a one dose vaccine that is 60% effective at preventing severe disease. But a booster shot will improve that into the 90% area the same as the 'double dose'.

So I fed all this back into the discussion and noted that it was incomprehensible that the J&J was not 'sold' as a two dose vaccination plan all along, just like the others.

Later, I read somewhere that President Biden had said the same exact same thing within hours of me.

It must be that my vaccine is working cause the 5G signal is getting through to the White House loud and clear.

[Sam the Centipede]

It was assumed early on that J&J were promoting their vaccine as single dose because that significantly eases any program for delivering into arms: half the shots, half the appointments, half the effort. That will also be more attractive in countries with less-developed public health systems.

Bear in mind that WHO were saying after the pandemic first broke that anything over (iirc) 50% efficacy in a vaccine would be good. And all the vaccines, even the less efficacious ones, easily hit that target.

But, yes, it's clear that many/most vaccines for common diseases work best with a prime dose to kick things off then a second dose (it's not a booster!) to power up the immune response and diversify the immune memory. J&J fits the pattern. However, J&J approached the issue without the benefit of the hindsight we have now! It's not as though they have to expensively redesign the vaccine for a two dose regimen.

And now we are thinking of vaccines in terms of medium and long term control of the virus, whereas in early/mid 2020 we were focusing on short term use to dampen down the surging pandemic.

Some polio vaccines have issues, because the live vaccine can revert to wild type. If I recall correctly (that's a big if!), some (all?) of the vaccines prevent the poliovirus from entering the bloodstream but they don't affect it in the gut. So a person can be infected, carrying the virus in the gut, where it can multiply, and hence spreading it if hygeine measures are inadequate, while being disease-free because the virus can't get a foothold in the bloodstream to move further around the body.

One of the barriers to vaccine development for older diseases is that incentive to develop a new vaccine is often low, and the performance and cost hurdles that vaccine has to jump are high: it must be better than the existing vaccines, not just better than no vaccine. Covid has been very unusual in that we now have about 12 different high-quality vaccines using 5 different technologies, a real blessing.

[keith]

Some polio vaccines have issues, because the live vaccine can revert to wild type. If I recall correctly (that's a big if!), some (all?) of the vaccines prevent the poliovirus from entering the bloodstream but they don't affect it in the gut. So a person can be infected, carrying the virus in the gut, where it can multiply, and hence spreading it if hygeine measures are inadequate, while being disease-free because the virus can't get a foothold in the bloodstream to move further around the body.

Yeah, I had that conversation a few years ago too, also. I don't remember the exact detail the entire issue now, but I think the multiple strain vaccine they use in some countries (not USA, USA uses a single strain vaccine) can sometimes recombine in the gut to produce a viable polio virus that can be transmitted and cause disease. So the anti-vax argument was that it was the vaccine that was spreading the disease in this case.

The thing is though, that vaccine DOES protect against infection, the vaccinated are protected against the 'recombined' virus just as they are against 'wild' virus. So it is only dangerous to the unvaccinated. AND, the 'recombined' virus is transmitted through feces. So to catch the virus in this way means you have to be unvaccinated and be playing around in the feces of people who have been vaccinated with the tri-valent vaccine.

BUT the recombination in the gut is vanishingly rare, and fortunately, such horrendously unsanitary conditions are also rare. I'm thinking refugee camps are probably pretty unsafe, but I cannot remember hearing of polio outbreaks anywhere.

So, sure, it can happen. That's why polio can't be declared 'eradicated'.

EDIT: I looked it up. The most recent polio outbreak in a refugee camp was in 2013 in Kenya. There are hundreds of cases per year from Africa, Eastern Mediterranea, Europe, and the Western Pacific. The 'recombined' virus I described above is actually called 'Circulating Vaccine-Derived Polioviruses'.

[Sam the Centipede]

Thanks Keith, I had also forgotten the details, just remembering a discussion between experts which confused me but wanted to send up saying that we shouldn't worry our pretty little heads too much but it was important to keep vaccinating partly because of this occasional reversion to wild type.