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grayray

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Is see on the BBC that the UK Government has ordered another 60 million doses of the Pfizer vaccine for a “Booster Program” planned for the Autumn. 
A sensible move IMHO. 
 

For some reason I couldn’t copy the link over to the forum. ☹️
 

 

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5 hours ago, Lemondropkid said:

True.

Pretty sad state of affairs where people are so twisted that others misery and suffering is used to support crackpot theories, and political views.

This isn't a comment aimed at your personally.  You come across as a decent guy, who'd front up in real life, want to meet people and have a beer with them.

 

4 hours ago, Krapow said:

Yes, @Mr. Smooth is on the 'want to meet at some stage' list!

He reminds me a lot of Bruce Mangosteen, who i certainly didn't always agree with on a forum, though class as a mate IRL, and have met many, many times, still converse with on Assbook as he calls it, and is a great guy and man of integrity. 

Thanks guys, feeling is mutual!

Lets hope it's sooner rather than later.

Cheers! 🍻

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23 minutes ago, KhunDon said:

Is see on the BBC that the UK Government has ordered another 60 million doses of the Pfizer vaccine for a “Booster Program” planned for the Autumn. 
A sensible move IMHO. 
 

For some reason I couldn’t copy the link over to the forum. ☹️
 

 

I think you might just be changing your mind when booster dose 3-4-5-6-7-8-9 ? come rolling around....And the requirements to take them...

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I think that having an annual or even bi annual booster is a small price to pay, if it means both keeping safe and keeping the virus to acceptable levels. Maybe acceptable is the wrong word but at a level where we longer need to lock down, far less hospital admissions and deaths. If a reliable drug for treating severe Covid infections then even better. 

If it proves necessary for regular booster jabs to fight against Covid mutations and variants then it will be far more viable than recent measures. We have science on our side to fight an invisible enemy that threatens our way of life

Vaccinations take a few seconds and can be administered at Pharmacies or almost anywhere for that matter and does not require a great deal of skill as it is just a needle into soft tissue. People could get it done in their lunch break and carry on working. 

 

 

 

 

 

 

 

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3 hours ago, Nightcrawler said:

I think that having an annual or even bi annual booster is a small price to pay, if it means both keeping safe and keeping the virus to acceptable levels. Maybe acceptable is the wrong word but at a level where we longer need to lock down, far less hospital admissions and deaths. If a reliable drug for treating severe Covid infections then even better. 

If it proves necessary for regular booster jabs to fight against Covid mutations and variants then it will be far more viable than recent measures. We have science on our side to fight an invisible enemy that threatens our way of life

Vaccinations take a few seconds and can be administered at Pharmacies or almost anywhere for that matter and does not require a great deal of skill as it is just a needle into soft tissue. People could get it done in their lunch break and carry on working. 

 

 

 

 

 

 

 

👍

 

Walk in the park compared to the alternative. 

 

Can't understand those that spew against it. Simply not rational people IMO and can stay far away from me.   

 

:default_1087::default_1263:

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20 minutes ago, Glasseye said:

👍

 

Walk in the park compared to the alternative. 

 

Can't understand those that spew against it. Simply not rational people IMO and can stay far away from me.   

 

:default_1087::default_1263:

Yeah, if I have to take an annual Covid shot then I am all for it - I never used to get flu shots and still don't bother, but it's just because I haven't had the flu for years and am not worried about it; but if I need Covid vaccinations to supposedly stay healthy and still travel, bring it on by all means!!

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29 minutes ago, maipenrai said:

Yeah, if I have to take an annual Covid shot then I am all for it - I never used to get flu shots and still don't bother, but it's just because I haven't had the flu for years and am not worried about it; but if I need Covid vaccinations to supposedly stay healthy and still travel, bring it on by all means!!

Heck.... I'll never forget the week I spent on my back in sheer agony from the flu about 30 years ago. I have been getting a free flu shot every year since. Will gladly do the same with covid. No brainer.

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1 hour ago, Glasseye said:

👍

Can't understand those that spew against it. Simply not rational people IMO and can stay far away from me.   

 

:default_1087::default_1263:

I guess central London is not a safe place to go with all these anti-covid protester having so many rallies there.....

Anti-lockdown protesters gather in London calling coronavirus a 'hoax' -  Daily Record

Dozens of arrests as thousands march in London against Covid lockdown |  London | The Guardian

Edited by fforest
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11 minutes ago, fforest said:

I guess central London is not a safe place to go with all these anti-covid protester having so many rallies there.....

Looks like a pack of anti 5G nut jobs as well.

With those types on the loose probably nowhere is safe.

 

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12 hours ago, Horizondave said:

Good news. Sad also the fact that they are influencing many other morons who probably found it all very funny.

 

Anyone who calls themselves a social influencer should be deported,glad to read this,i hope they will spend a sleepless night in the airport detention centre,the sorts often seen in bangkok,attempting to play a bongo drum and fuckin spoons with a sign that reads" please help us with our travel adventure around asia" good riddance.

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7 hours ago, fygjam said:

Looks like a pack of anti 5G nut jobs as well.

With those types on the loose probably nowhere is safe.

 

Jeremy Corbyn's brother Piers is one of their leading lights.

Stupidity must run in the family.

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11 hours ago, fforest said:

I guess central London is not a safe place to go with all these anti-covid protester having so many rallies there.....

Anti-lockdown protesters gather in London calling coronavirus a 'hoax' -  Daily Record

Dozens of arrests as thousands march in London against Covid lockdown |  London | The Guardian

Great day out!

I made a fortune at it selling a special Covid edition of the Flat Earth Society fortnightly magazine entitled -

'Just because you're a paranoid schizophrenic doesn't mean they're not trying to change your DNA to turn you into a Capuchin monkey' 

Only problem was getting home with all the cash, they wouldn't use card as that was 'part of the cashless one world government plot, man!'

Still, gave me an idea for next fortnights magazine.

Stay Safe! 

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2 hours ago, Krapow said:

Great day out!

I made a fortune at it selling a special Covid edition of the Flat Earth Society fortnightly magazine entitled -

'Just because you're a paranoid schizophrenic doesn't mean they're not trying to change your DNA to turn you into a Capuchin monkey' 

Only problem was getting home with all the cash, they wouldn't use card as that was 'part of the cashless one world government plot, man!'

Still, gave me an idea for next fortnights magazine.

Stay Safe! 

They've got convictions of iron these protestors .

Mate of mine owns a pub in Hull where there was a protest between our various lockdowns.  6 of them came ordered there drinks but hadn't given any contact details

My mate asked them nicely, one of them started to go off on one. He told them again maintaining civility, they could either stay and provide their details or get out.

5 of these men of iron filled out their addresses and number, and the mouthy one stormed out😄.  Deep State 1, Decent Pint of Ale 5 🍻

All piss and wind.

Edited by Lemondropkid
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35 minutes ago, Glasseye said:

Pandemic math.... easily explained, easy to follow.

**** Non mask wearers don't bother. It's unlikely that you'll be able to comprehend.

https://www.nytimes.com/2021/04/29/opinion/covid-exponential-decay.html?action=click&module=Opinion&pgtype=Homepage

Good article. It may be behind a paywall for some, which it was for me. Chrome's incognito window is an easy way around the paywall.

Key takeaway from the article...

It is possible to bring Covid-19 case numbers down quickly via exponential decay even before vaccination rates reach herd immunity. We just need to keep transmission rates below the tipping point between exponential growth and exponential decay: where every person with Covid-19 infects fewer than one other person, on average. Every single thing people can do to slow transmission helps — including wearing masks, getting tested and avoiding crowded indoor spaces — especially given concerns about current and future variants, since it could be what gets us past the threshold into exponential decay.

Edited by forcebwithu
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16 minutes ago, forcebwithu said:

Every single thing people can do to slow transmission helps — including wearing masks, getting tested and avoiding crowded indoor spaces

Sort of like a self imposed mini lockdown really.

Mandated lockdowns, stop or prevent exponential growth.

Personal responsibility maintains exponential decay.

 

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Sciency shit. If you don't like it then don't read, just fast forward to the next post.

In a previous post I said that if I had a choice of the 2 vaccines currently being rolled out in Australia I would choose Pfizer over AstraZeneca. (I don't have a choice at present although now that some over 50 yo people have popped their clogs after receiving AZ, who knows).

One reason for my preference was the "2P mutation", a human engineered mutation to the SARS-CoV-2 spike protein which in animal studies resulted in a more than six fold increase in the immune response compared to the wild virus. This mutation is used in the Pfizer, Moderna, J&J, Novavax vaccines among others. It is not used in the AZ vaccine. Actually, there doesn't seem to be any information in the public domain as to the spike used by AZ.

The following is a fairly easy to read article on the discovery of the 2P mutation. If you want it with pictures, a link to the original article is at the end.


The tiny tweak behind COVID-19 vaccines

Prepandemic coronavirus research by Jason McLellan and Barney Graham
led to a trick for stabilizing the prefusion form of spike proteins

On Jan. 10, Chinese scientists uploaded the genetic sequence of a novel coronavirus, later
named SARS-CoV-2, to an open-access website, GenBank. The virus had been linked to a
growing number of mysterious pneumonia cases, and its rapid spread was beginning to raise
alarms. A few hours later, Barney Graham woke up and saw the sequence. Though it was a
Saturday, he got right to work.

Days before, his lab at the US National Institute of Allergy and Infectious Diseases (NIAID) had
partnered with the biotech company Moderna to design an experimental vaccine for the virus,
which causes the disease COVID-19. All they’d needed to start was that sequence.

Six months later, Moderna began testing that COVID-19 vaccine in a Phase 3 clinical trial of
30,000 people. Results are expected later this fall.
(This article was published at the end of September, 2020).

Neither Graham nor Moderna could have known then how truly catastrophic the novel
coronavirus would become. Two previous coronavirus outbreaks, which caused severe acute
respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)—both deadlier
but less contagious—were contained without global shutdowns and before vaccines could be
developed. So how did they make the COVID-19 vaccine candidate so fast?

It helps that Moderna’s vaccine is based on messenger RNA (mRNA), a genetic molecule that
scientists can synthesize more rapidly than the viral proteins or whole viruses used in
conventional vaccines. Moderna and Graham’s lab also had a template to work from because
they’d spent several years designing an experimental mRNA vaccine for the MERS
coronavirus.

But there’s a third, more subtle secret to their success: a tiny but oh-so-important tweak to a
critical viral component called the spike protein.

Viruses multiply by dumping their genes into our cells and hijacking our cellular machinery to
crank out new virus particles. But first, they need a doorway into our cells. Coronaviruses are
studded with spikes, which grab hold of proteins decorating our own cells like doorknobs. Once
attached, the spike undergoes a dramatic transformation, stretching before partially turning
inside out to forcefully fuse with our cells.

Scientists believe that for COVID-19 vaccines to be effective, our immune systems must develop
antibodies that prevent this fusion. Such antibodies must target the spike protein in its aptly
named prefusion conformation. Unfortunately for vaccine developers, spike proteins are liable
to spring from their stubby prefusion shape into their elongated postfusion form on a hair
trigger.

Fortuitously, Graham and a former postdoc, Jason McLellan, devised a solution to this problem
before the pandemic. Through a bit of structural biology and persistent protein engineering,
McLellan discovered that adding two prolines—the most rigid of the 20 amino acids—to a key
joint of a vaccine’s spike protein could stabilize the structure’s prefusion shape. This 2P
mutation worked in preclinical studies of Graham and Moderna’s MERS vaccine, so they
applied it to Moderna’s COVID-19 vaccine.

As Norbert Pardi, an mRNA vaccine scientist at the University of Pennsylvania, puts it, we’re
“very lucky, actually,” that scientists worked out the 2P mutation for a MERS vaccine before the
COVID-19 pandemic. “It wouldn’t be possible to go so fast with the Moderna vaccine
otherwise.”

Other companies, including Johnson & Johnson, Novavax, and Pfizer, are hoping the 2P
mutation works for their COVID-19 vaccines too.

The 2P mutation might quite literally be the smallest detail that could make or break the first
generation of COVID-19 vaccines. It’s an easy enough tweak to add during the early stages of
vaccine design. And if successful, 2P-based vaccines may herald a new generation of
vaccines whose molecular makeup is fine-tuned to craft a safer, stronger immune response.

CATCHING A SHAPE-SHIFTER

Vaccines are built on the premise that if you show immune cells a pathogen that they might
one day encounter in the wild, they should learn to protect against the disease. Older vaccines
present the immune system with an entire virus in a weakened or deadened form. More
contemporary vaccines are made up of only a piece of the virus—a certain critical protein that
should prompt the creation of antibodies that can shut down an infection. And the newest
vaccines, like Moderna’s, deliver mRNA that encodes instructions for making that viral protein.

Yet sometimes showing the immune system the viral protein, in any of these forms, isn’t
enough. Respiratory syncytial virus (RSV) is a prime example.

In the US, RSV sends an estimated 57,000 children under the age of 5 to the hospital each
year; some 14,000 adults older than 65 die from the virus. There’s still no vaccine available.

In 1966, a decade after RSV was discovered, US National Institutes of Health researchers
began testing an RSV vaccine made of a virus killed with formalin—an aqueous solution of
formaldehyde. The trial was a disaster, McLellan says. Although infants who got the vaccine
developed antibodies against the virus, they were not protected from infection. Instead, the
vaccine seemed to make the disease worse. Some 80% of infants who got the shot were
hospitalized after an RSV infection, compared with 5% of infants in the control group. Two
vaccinated babies died from the infection. The tragedy tainted the RSV vaccine field for
decades.

Scientists now know that RSV infects and fuses with human cells using its F protein, which,
like coronavirus spike proteins, shape-shifts during infection. The F protein is far more
unstable than spike proteins, and in 2016 Graham reported that formalin inactivation leaves the
viruses coated with postfusion F. Our immune systems can make antibodies against postfusion
F, but they aren’t very good ones.

The best antibodies prevent infection. These neutralizing antibodies are the goal of vaccine
developers. Animal studies suggest that the initial RSV vaccines induced antibodies that
bound to postfusion F but failed to neutralize the virus, leading to inflammation, clogged
airways, and more severe disease than with no vaccine at all.

In theory, a vaccine based on the prefusion F should solve this problem.

RSV wasn’t the only virus that seemed impervious to vaccination. In particular, the inability to
stop HIV with vaccines pushed biologists to start tinkering with the structures of viral proteins
in an attempt to engineer a better immune response.

McLellan joined NIAID as a postdoc in Peter Kwong’s lab in 2008 to do that work with HIV, but
he soon realized he was up against the hardest test case for these protein-engineering
principles. Graham, who, as the deputy director of NIAID’s Vaccine Research Center, worked
in the same building, encouraged McLellan to work with him on RSV. If they could find a way to
modify the F protein and keep it locked in its prefusion form, they might have a shot at creating
a successful RSV vaccine.

Figuring out exactly what the prefusion F protein looked like was their first challenge. McLellan
and Graham decided to look for antibodies that neutralize RSV but don’t bind postfusion F.
Such antibodies were likely binding to prefusion F, they reasoned, and could thus be used to
lock the protein down. Doing so would allow McLellan, a trained X-ray crystallographer, to
capture a snapshot of the prefusion F and antibody bound together. The team found three
highly potent neutralizing antibodies that fit the bill.

The resulting picture explained why the older RSV vaccines had failed. The antibodies clung to
the very tip of the prefusion F, a foothold that disappeared during the protein’s metamorphosis
as it fused to its host cell.

The team embarked on a large protein-engineering effort to create more than 100 variants of F
to find modifications that stabilized the prefusion form. McLellan found that swapping out two
serines for cysteines introduced a disulfide bond that, like tape, helped hold the protein in
place. The researchers made it even stabler with a second tweak—replacing two amino acids
in its inner cavity with hydrophobic residues. “We created a vaccine molecule that couldn’t
have been created without structural information,” McLellan says.

That molecule, called DS-Cav1 and published in Science in 2013 (DOI:
10.1126/science.1243283), induced 10 times the level of neutralizing antibodies as a vaccine
with postfusion F did in a study with rhesus macaques. Several companies, including
GlaxoSmithKline, J&J, Moderna, and Pfizer, are developing RSV vaccines that rely on
prefusion-stabilization mutations.

“The RSV work showed that the protein sequence is not nearly as important as the protein
conformation,” Graham says. In other words, a vaccine might contain or encode the right
protein, but if that protein isn’t in the right shape, it won’t work. “This really changes the way
you think about designing a vaccine.”

STABILIZING THE SPIKE

After early signs of success with the RSV vaccine, Graham and McLellan were eager to apply
their techniques to another virus. As McLellan was starting his own lab at Dartmouth College in
2013, the recently emerged MERS coronavirus was top of mind. No one had ever solved the
structure of a full coronavirus spike protein. These proteins are similar to the F protein on RSV
but a whopping 2.5 times as large.

Despite many attempts, and even with outside help, the scientists couldn’t get the MERS spike
protein to cooperate. So McLellan, Graham, and their collaborator at Scripps Research,
Andrew Ward, turned to a different coronavirus, HKU1. The virus, which causes the common
cold, was safer to work with and better at sitting still while its picture was being taken. In 2016,
Ward’s lab used a technique called cryogenic electron microscopy to capture the structure of the
HKU1 spike.

McLellan and his team scoured the structure for clues that could help them stabilize the MERS
spike protein. They homed in on a region toward the top of the spike, a small loop of amino
acids that held two coil-like structures called α-helices together.

“It is like a spring bent in half,” McLellan says. When the spike protein binds to a human cell,
that spring is released, and the two helices and the loop straighten into one long helix that
harpoons the human cell and pulls the virus and human membranes close together until they
fuse.

Blocking the release of that spring should prevent viral fusion, giving the immune system a
chance to make antibodies that prevent infection, they theorized. McLellan’s lab tried several
tricks before arriving at one that worked: adding two prolines in the loop between the two
helices clamps the spring together. This 2P mutation enabled McLellan and Ward to solve the
MERS prefusion spike structure in 2017 (Proc. Natl. Acad. Sci. U.S.A., DOI:
10.1073/pnas.1707304114). Graham began working with Moderna to make an mRNA vaccine
for MERS using the 2P mutation that same year.

Once the genetic sequence of SARS-CoV-2 was released this January, Graham’s lab,
collaborating with McLellan’s lab, was able to compare its genome with those of SARS and
MERS, pinpoint the code corresponding to that bent spring, and then add the 2P mutation to
lock the SARS-CoV-2 spike in its prefusion conformation.

Several other companies developing COVID-19 vaccines are also using the 2P mutation. Dan
Barouch, a Harvard Medical School vaccine scientist working with J&J on its COVID-19
vaccine, tested six versions of the vaccine in 35 monkeys. The spike protein vaccine with the 2P
mutation performed the best. “It looks promising,” says Bing Chen, a virologist at Harvard
Medical School who was part of the study. But he cautions that the 2P mutation didn’t make a
huge difference, and even if it is the best option, there’s no guarantee it will work as well in
humans.

After rapidly determining the structure of the SARS-CoV-2 prefusion stabilized spike protein in
February, McLellan’s lab continued to tinker with the spike protein. After testing more than 100
variations, he published a new version in July called HexaPro (Science 2020, DOI:
10.1126/science.abd0826). It contains the original 2P mutation plus four additional prolines
that further stabilize other regions of the protein. His preliminary results suggests the molecule
might be 10 times as potent as 2P.

“There is probably no limit to how much more we can keep going or how much time we can
keep spending,” McLellan says, but he’s happy with HexaPro. The HexaPro gene has been
shipped to dozens of labs, and multiple vaccine companies are already conducting lab tests of
HexaPro as part of a second-generation COVID-19 vaccine, he adds.

The use of the 2P mutation in coronaviruses is the subject of a patent application filed in 2017
by NIAID, Scripps, and Dartmouth. NIAID and the University of Texas at Austin, where
McLellan is now an associate professor, filed another patent early this year. So far, those
patent applications are not preventing anyone from using the trick, but the early government
investment that made 2P-based vaccines possible could add fuel to debates about how
government-funded research should influence vaccine pricing.

It’s too soon to say if Moderna’s vaccine or any of the other front-runners will be successful.
Even if they are, the 2P mutation won’t be the only reason, and it might not even be the most
important. One of the COVID-19 vaccine front-runners, produced by AstraZeneca, doesn’t
even use it.There are countless ways the novel coronavirus has caught us unaware, but if the
2P mutation turns out to be helpful, it may be one of the few preparedness success stories of
the pandemic.

“We started quickly because we had an idea of what to do ahead of time,” Graham says. “I
think this whole episode is going to change how we think about vaccines going forward.”

UPDATE

This story was updated on Oct. 1, 2020, to clarify that Graham's lab and McLellan's
lab were both involved in the early design of Moderna's SARS-CoV-2 vaccine.

https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38

There are some other interesting Covid-19 links at the same website.

 

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