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Why Are Double Vaccinated Getting The Delta Variant?

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sevenOP | 10:54 Fri 17th Sep 2021 | Science
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If it is a change in the spike protein do we know how and what exactly has changed?
And the early claims from the mRNA manufacturers was they could 'tweak' the vaccine easily in a few weeks so is that happening?
Genetic sequencing has been going on aplenty and Britain is said to be a world leader in it, so we should have good data by now.

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Noone is immune from any variant even if double jabbed but its less effective for delta
Yep, we know exactly what has changed in respect of the delta variant.
To begin with, there are multiple gene mutations in what are known as Receptor Binding Domains which you can regard as the part of the spike protein that binds to ACE2 receptors. There are three mutations here in the delta variant at positions 417, 452 and 478. The effect of this change is that the variant can bind more easily to its target.
Secondly, there are changes in what's known as the Furin Cleavage Site. Here, the spike protein must cleave (separate in this case), two parts of itself to allow it to fuse to a membrane and cause infection. At position 681, an amino acid substitution makes the whole structure less acidic and causes the cleavage to occur far more easily. This means that more spike proteins can enter human cells. In fact, the increase is between 70% and 80% in terms of other variants. In a nutshell, this means the delta variant is both more transmissable and more infectious as long as other substitutions have occurred.
So far I've discussed substitutions in the delta variant but there is something even more clever happening.
Parts of the spike protein are more likely to be attacked via recognition by antibodies. These sites are called NTD Antigenic Supersites. The delta variant contains substitutions at points 19, 142 and 158 but there is a deletion of amino acids at positions 156 and 157. This change substitution/deletion combination means that the virus has increased its ability to evade immune detection.

I've not explained the meaning of every term I've used above or the post would become ridiculously lengthy and you'd fall asleep while reading it. Google may be your friend here. I've also simplified it considerably for the same reason.
The word "cleave" has two precisely opposite meanings depending on the context in which it is used. It can mean to pull apart or to join. In the context I've used, it means to pull apart or separate.
We do indeed have a pretty good idea of how these changes have happened sevenOP but explaining it needs some considerable understanding of the virus. If you were in front of me in a lecture hall, I'd give it a bash but it can't be done on AB.
I won't discuss current trends in vaccine tweaking apart from the fact that the scientists involved are on top of the matter. There are no changes in the development timescale.

We are indeed at the forefront of genetic sequencing in the UK and we have an incredible range of data to hand regarding all virus variants. This data is used by the vaccine developers constantly via a huge online database and the data remains vital for vaccine development the world over.
I'd be very interested, if theprof, has time to explain further.
In my view, I would expect more variants, particularly with more vaccinations... it has to evolve to survive.
OK pixie374, I'll try to explain.

All RNA viruses mutate over time. This includes the SARS variant responsible for the covid pandemic. We've been accustomed to this behaviour for years.

The coronavirus will continue to mutate throughout the world for as long as the infection spreads. That's the bottom line and I should underline the last sentence. New variants are detected daily and I and my team have discovered our fair share during our involvement with this virus. However, this in itself is not a major cause for concern for specific reasons; some variants for example, appear in huge quantities in genome sequencing sampling but then disappear in a matter of days in the same population; others may be confined to specific countries but go no further; others become less infectious. It can sometimes be very difficult to conclude why these patterns and others are emerging but it's for greater minds than mine to decide why this occurs.

Right now there are variants that are under investigation that are concerning. These are not necessarily "variants of concern" that you may have read about but I won't go into that as it can be very confusing. The variants are classified using a continuation of the Greek Alphabet and are known as Eta, Iota, Kappa and Lambda. To complicate things further, there are sub-variants of these four too

We are not more at risk from these variants per se. A variant that spreads easily may indeed have an advantage. However, a variant that is more fatal to us as a population, will not have the time or ability to spread further once the "host", namely us, are dead. It therefore cannot infect others as long as precautions are observed and it will eventually die itself. That's a good thing.

Nine new variants have been added to the online database in front of me on my laptop since I started typing this on my tablet and some variants have disappeared, possibly temporarily or maybe not. It's an ever changing situation.

I'm still actively involved with this virus on a daily basis in the UK and abroad. I returned from a USA University on Wednesday after spending eight days there advising them on interpreting sequence changes in a variant that had suddenly appeared in the population. The sequence change was unknown 17 days ago. These things happen that quickly sometimes

I'm privileged insofar as my work allows me to fly to the USA during this crisis to advise where I'm needed but I still can't take my grandchildren to Disneyand no matter how much I badger the US embassy! Seriously though, I'm fully supportive of the restrictions in place.

Right now there are some issues concerning the Delta variant and the effectiveness of selected vaccines throughout the world but I'm confident that the vaccine developers and immunologists can resolve the issues.





Brilliant, thank you, theprod.

On a personal note, it would be very helpful if you could give some insight into when Brits will be allowed back into the USA for a holiday, especially those double vaccinated with Astra Zeneca, and especially if one of the doses was one of the three unapproved AZ batches!
theprof*!!!
Ellipses, I would really like to help but I've no idea. I've been over the States a few times since January last year but it's all been in an academic capacity. I was initially asked to take part in zoom meeting and suchlike but I told the authorities I was not prepared to comply when we had a worldwide pandemic on our hands. I suppose the fact I'm a visiting Prof at various Ivy League universities makes a difference along with documents signed by Uncle Joe and his predecessor.

As I understand, the USA position is reviewed more often than they admit. I've no idea how it will work or when but I don't think that we will wake up one morning with everything having returned to normal. Quite rightly, their primary concern is their own citizens and they are keen to keep variants out of the country. Consequently, for reasons I've cited above, conventional vaccination documents cut no ice with them.

I can tell you that I've been fully jabbed with all the vaccines you'll have heard of including the Chinese one along with booster jabs where necessary. These jabs were necessary because I work with dangerous pathogens. I've been tested umpteen times a week since I began. The daily testing regime was diabolical. Despite all this, there was a time when it was touch and go whether I'd be allowed to travel but the paperwork now says I'm needed.

Sorry, I can't be more helpful.

Thank you, theprof, appreciated x
Many thanks

very clear
oh,

However, a variant that is more fatal to us as a population, will not have the time or ability to spread further once the "host", namely us, are dead.

a.is observed in every epidemic -in porton down speak 1970 - passage thro the human host makes an infectious agent more virulent

b. Prof Rushton Bham around the small pox incident: - "dont ask me I have no idea why ..." an agent gets more virulent - 'makes no sense at all to kill the host'

c. 1347 - no epizootic desribed - plague could have been pneumonic

d. 1685 - Defoe notes that those coughing red sputum at the end were much more infectious ( = rat + flea not needed,)

and I thought..... the S pool ( SIR simple model as I am simple teddy bear ) is contracted basically by immunisation, so the virus HAS to get more virulent in order to survive ( that is if you DON'T get more virulent then the epidemic terminates ) so the only ones that go on and on.... are more virulent.

my little contribution to science

Porton Down? 1976 VizosoAD B virus - and yes I go nowhere near pet monkeys. Can never remember if it is new world or old world that are the killers.

I only wrote this to show I understood what you wrote
thank you for your help in saving the world and - - - spending time on AB, keeping us up to date
The experts can give all the advice in the world but who gets to travel where and when is a political decision which may or may not follow that advice.
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Thank you for your time theprof.

So with the delta variant, is it only the spike that is changing i.e, not the viral RNA that is being injected via the spike ?
And so is it just an increased viral load, and speed of increase in viral load that is causing increased damage compared to the wild original virus?
SevenOP, no, it's not just the spike protein that is changing. Changes are happening elsewhere on the virus. These include mutations in the nucleocapsid proteins that surrounds the RNA genome that we suspect are working in tandem with spike protein mutations resulting in the virus having the ability to evade antibodies which in turn affects the effectiveness of vaccines.

Spike protein changes are well documented not least because most research has been geared up to study them in detail. Spike protein changes tend to be the most clinically important changes in the virus so it's sensible to study what's going on there as a priority.

To give you some examples of changes elsewhere on the virus, there are mutations that have improved virus assembly in the delta variant bypassing a flaw during the original method of assembly. Another mutation has allowed the virus to make changes to a structure called the Golgi Body in cells, which processes and packages lipids and proteins. Another change has deleted an inbuilt error that has resulted in very oddly deformed virions in isolated cases, improving the very roughly estimated one in a million virion assembly error rate.

Some of these changes occur in the delta variant and some in the delta plus variant, which is slightly different to delta as it has a mutation at K417N on the spike protein. Others mutations occur in all variants.

As a result of the above, I hope you can see that it's not all down to increased viral load.
Thank you Peter.

Macacine alphaherpesvirus 1 is a particularly virulent vicious species and there are still samples in Porton Down. It's confined to old world monkeys, mainly the 20 + species of macaques. There remain strict regulations for any researcher working with macaques in most of the Western world but fatal accidents have occurred elsewhere so I don't blame you for avoiding monkeys!

Your virulence comments are appreciated.
THECORBYLOON, 'twas ever thus.

Countless times during this pandemic I've been invited to elevate my status by spending hours sitting round a table where jaw jaw is the order of the day.

I've always politely declined. I'm a scientist not a politician and I leave the decision making to others. Those that have one foot in each camp are asking for trouble as has been evident over the past few months. I don't need the publicity.

// I'm a scientist not a politician and I leave the decision making to others.//

I thought it had been handled quite well - presumably the people speaking out of turn had their hands cut off. Sticking admirably to the idea of the scientists do the science and the politicians take the political decisions

( unlike the land of the free where at one point Trump called Fauci a dumb son of a botch )

// the viral RNA that is being injected via the spike ?//
I thought RNA went down the receptor but it doesnt
google furin cleavage
https://www.nature.com/articles/s41564-021-00908-w
there is an awful lot on You tube - hour lectures where you think - "well I understand that but it isnt really of use ...."

cell fusion - and then an awful lot of the fate of mRNA in the cell cytoplasm. another splurge of information and you think - "oh it does that does it ..."
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I realise trying to make understandable to the general Public the way the SARS-CoV-2 infects and spreads is simplifying a highly complex process; is the viral RNA in communication with the Spike, Capsid, Membrane and Nucleocapsid proteins so the RNA protein can alter. or, does the infected cell 'read' the viral RNA Spike, Capsid, Membrane and Nucleocapsid proteins and then make copies ?
( this comes from cartoon/simplified explanation like 'S,C,M and N proteins allow entry, whereas only viral RNA only is copied... please excuse my layman's interpretation)
Thank you, theprof. I am by no means a scientist (Eng. Lit./Art/Art History/History), but know a bit about biology etc.. I certainly didn't follow every word you wrote by any means, but it has made matters much clearer to me. If only we had all this explained on the radio or T.V., perhaps in smaller, more digestible chunks. I am grateful to you anyway and will re-read and re-read. :)

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