Vaccine and T-cell response

Treatments and their effectiveness, herd immunity, masks, testing, etc.
Jane G
Posts: 198
Joined: Wed Sep 02, 2020 6:29 pm

Vaccine and T-cell response

Post by Jane G »

There has been bickering on twitter about Coronavirus supposedly being able to reinfect those who have previously had it, and vaccination is still needed to boost immunity.
Does anyone have any information about whether we develop T cell response after vaccination on previously UN- infected people, or does it only happen after exposure to the virus?

Splatt
Posts: 1576
Joined: Thu Oct 29, 2020 12:46 am

Re: Vaccine and T-cell response

Post by Splatt »

For Oxford:- https://www.nature.com/articles/s41591-020-01194-5

For Pfizer:- https://www.nature.com/articles/s41586-020-2814-7

Worth noting that (simplified explanation) T-cells don't stop reinfection. They target already infected cells.
The protection inferred is not preventing infection its reducing its length and severity once infected.

Reinfections remain at an incredibly low level compared to other HCoVs. That level would appear to be much higher in the SA/BrazilNigeria/Kent v2 variants though. They do show a good level of immune escape as well as a significant reduction in vaccine efficacy (to the extent Oxford is essentially zero protection).
Again this is expected and will happen more and more as vaccination progresses.

Jane G
Posts: 198
Joined: Wed Sep 02, 2020 6:29 pm

Re: Vaccine and T-cell response

Post by Jane G »

Many thanks for the links, Splatt - some reading for this evening.

guy153
Posts: 48
Joined: Wed Apr 22, 2020 5:29 pm

Re: Vaccine and T-cell response

Post by guy153 »

Splatt wrote: Sun Feb 28, 2021 12:29 pm For Oxford:- https://www.nature.com/articles/s41591-020-01194-5

For Pfizer:- https://www.nature.com/articles/s41586-020-2814-7

Worth noting that (simplified explanation) T-cells don't stop reinfection. They target already infected cells.
The protection inferred is not preventing infection its reducing its length and severity once infected.

Reinfections remain at an incredibly low level compared to other HCoVs. That level would appear to be much higher in the SA/BrazilNigeria/Kent v2 variants though. They do show a good level of immune escape as well as a significant reduction in vaccine efficacy (to the extent Oxford is essentially zero protection).
Again this is expected and will happen more and more as vaccination progresses.
Yes great explanation. The T-cell response from the vaccines, especially CD8+ T-cells, is particularly important and is the reason for using mRNA and vector vaccines. Inactivated whole virus vaccines are much worse at doing that.

I would much rather have a few of those T-cells than a ton of antibodies without them.

Splatt
Posts: 1576
Joined: Thu Oct 29, 2020 12:46 am

Re: Vaccine and T-cell response

Post by Splatt »

guy153 wrote: Wed Mar 10, 2021 10:29 am Yes great explanation. The T-cell response from the vaccines, especially CD8+ T-cells, is particularly important and is the reason for using mRNA and vector vaccines. Inactivated whole virus vaccines are much worse at doing that.
Swings and roundabouts though.
All the mRNA and vector vaccines currently just use the spike (or bits of it). This makes them far more prone to immune escape with a small number of mutations.
Inactivated provides far far more epitopes to be recognised which will make them less likely to be knocked out by a mutation. Important if your goal is to reduce or prevent infection (rather than just knock it out once it happens).

My main concern still remains the small, very precise area our vaccines are targeted on. We've never gone down this precision route before.
That said there are several under development due next year which hope to address that issue.
We probably should be looking at other, more conserved surface proteins or similar to add as extra targets.

guy153
Posts: 48
Joined: Wed Apr 22, 2020 5:29 pm

Re: Vaccine and T-cell response

Post by guy153 »

Splatt wrote: Wed Mar 10, 2021 1:59 pm Swings and roundabouts though.
All the mRNA and vector vaccines currently just use the spike (or bits of it).
This makes them far more prone to immune escape with a small number of
mutations.
It's not super-important for antibody epitopes as all the important
neutralizing ones are on the spike.

It might be worth having some TCR epitopes for non-spike parts but I think
people are worrying too much about immune escape. The total number of TCR
epitopes is somewhere in the thousands (of which ~100s or so are on the spike).

It's going to take a lot of mutations to escape those.
Splatt wrote: Wed Mar 10, 2021 1:59 pm Inactivated provides far far more epitopes to be recognised which will make
them less likely to be knocked out by a mutation. Important if your goal is to
reduce or prevent infection (rather than just knock it out once it happens).
Idk about far far more. The whole genome of SARS-CoV-2 is about 10,000 amino
acids long, and the spike is about 1000. So it's about 1/10 of the whole thing.

Antibodies to non-spike parts of the virus won't prevent infection anyway. The
virus can escape total sterilizing immunity with relatively few mutations to
key epitopes whatever you do (and this is sure to happen in a few years, by
which time antibody levels will be low anyway). But it's not going to escape
everything, and this will result in mild reinfection and an update of the
host's immune memory.

I think based on the research that was done on vaccine enhanced disease for
SARS1 that a Th1-biased response with plenty of CD8+ T-cells is really
important. Much more so than headline efficacy figures.

There are also some indications that including the N protein in the vaccine can
actually be harmful:

https://jvi.asm.org/content/85/23/12201

See in particular the part where they discuss "Vaccine-induced eosinophilia is
a common feature of N proteins across group 2b coronaviruses", near the end.

This is talking about SARS1 but SARS2 has a very similar N protein.
Splatt wrote: Wed Mar 10, 2021 1:59 pm My main concern still remains the small, very precise area our vaccines are
targeted on. We've never gone down this precision route before. That said
there are several under development due next year which hope to address that
issue. We probably should be looking at other, more conserved surface proteins
or similar to add as extra targets.
I'm not so worried about that. But we'll see!

Jane G
Posts: 198
Joined: Wed Sep 02, 2020 6:29 pm

Re: Vaccine and T-cell response

Post by Jane G »

Am considering blowing some earnings on a trip to Harley St for one of the blood-tests that checks for presence of T cells against C19. Can't find anywhere else that does it.

Pricey, especially with the train fare - but nothing else to spend it on. Husband thinks it's silly but if I feel I must...
The risk is of course that I may be deficient in the little chaps; in which case I will have frittered a couple of hundred quid on some bad news. (Mind you, last time I went to London was the occasion I think I picked up the lurgy)

Just putting it out there in case anyone else has had this test, and if they have anything to report?

JohnK
Posts: 64
Joined: Sat Mar 13, 2021 12:47 pm

Re: Vaccine and T-cell response

Post by JohnK »

Jane G wrote: Wed Apr 28, 2021 11:55 pm Am considering blowing some earnings on a trip to Harley St for one of the blood-tests that checks for presence of T cells against C19. Can't find anywhere else that does it.

Pricey, especially with the train fare - but nothing else to spend it on. Husband thinks it's silly but if I feel I must...
The risk is of course that I may be deficient in the little chaps; in which case I will have frittered a couple of hundred quid on some bad news. (Mind you, last time I went to London was the occasion I think I picked up the lurgy)

Just putting it out there in case anyone else has had this test, and if they have anything to report?
I hope it turns out to be useful. I’m aware of the organisation you mentioned, having seen their adverts. It appears that they would use this method: https://www.tspotcovid.com/ I don’t know if it’s in use anywhere else, though. Logically, if it was the norm to do this first before offering a novel ‘vaccine’ product, it would minimise the risk to the individual - albeit with reduced sales of the product on offer.

Nobody
Posts: 289
Joined: Fri Nov 20, 2020 12:05 pm

Re: Vaccine and T-cell response

Post by Nobody »

Personally, I wish I could find a way to contract the virus, then I would have life-long immunity of some form. Pity the lockdown, and my isolation, ensured I had no chance of getting it.

thinksaboutit
Posts: 675
Joined: Wed Jan 06, 2021 11:38 am

Re: Vaccine and T-cell response

Post by thinksaboutit »

Nobody wrote: Thu Apr 29, 2021 9:28 am Personally, I wish I could find a way to contract the virus, then I would have life-long immunity of some form. Pity the lockdown, and my isolation, ensured I had no chance of getting it.
This is the shortest post I have seen from you. Well done.

Why do you think you would get life-long immunity? I've never seen anyone claim that.

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