Thread by @MonicaGandhi9

Wanted to explain one more thing before I go for my break which is the difference between what T cells and antibodies do for you in terms of protecting you against COVID. T cells protect you against severe disease. We have already gone over how variants
rupress.org/jem/article/21…

unlikely to evade T cell immunity since 80-100 T cells line up across the spike protein so 10-13 mutations of variants can't evade that many T cells. You have the data in the T cell thread but here are the 2 best papers on this- 1st here
biorxiv.org/content/10.110…

Here is the 2nd paper on this. Variants can't evade our T cell response so we are protected against severe disease. That is why vaccines 92-100% protective against severe disease in the real-world or the trials variants or not
cell.com/cell-reports-m…

Okay to protect against more mild disease, you want your antibody response to be high. IgA and IgG antibodies cluster in the nose (there are T cell islands in the nose too and some of them go more into the nose but antibodies will immediately block the virus there).

So, delta variant needs 2 doses for full effect in order to boost antibodies to the degree to block symptomatic infection by 88% (seen in PHE data from England). More symptomatic breakthroughs were seen at first in the UK when they used a 1st dose 1st strategy when delta emerged

That is why UK shortened time between doses. So, this explains why breakthroughs are most often mild if someone is exposed to a variant as antibodies wane (which go into nose) but not T cells, so you rarely get severe disease with a breakthrough.

And the asymptomatic breakthroughs as we explained before after vaccination could just be dead virus in the nose which the PCR test is amplifying up - you need the CT value (cycle threshold) to tell if a real breakthrough or not. T cell thread could help

https://twitter.com/MonicaGandhi9/status/1373506320154849282

So why did delta spread more in UK than Israel - because UK used 1st dose 1st strategy (Israel 3 weeks between doses). UK saved lives: even 1 dose generates T cells, prevents severe disease. But need 2nd dose for delta to get Abs up in nose to limit both spread & mild infection.

At some point we will have to decide whether to follow severe disease outcomes now that vax is here (and whether to boost for more Abs in immunocompetent nose or follow T cells as correlate of protection- Senate likely to fund). Vax has changed everything about COVID monitoring

So, I have had strange replies re: T cells but I don't think people are remembering immunology; T cells and B cells are your two main arms of the immune system. B cells produce antibodies; antibodies wane over time (or blood would be too thick!); memory B & T cells stay around

This paper from @UCSF and others explain why T cells protect you from severe disease. So, a booster will boost antibodies & may be needed for immunosuppressed & elderly (like for many vax)- FDA will decide if needed for immunocompetent
cell.com/cell-reports/f…

Journalist asked yesterday -in light of delta, should we shorten duration between doses in places using 8-12 weeks; I would say yes. Because you may be protected from severe disease (which is why 1st dose 1st was life saving ), but need those 2 doses to boost Abs, decrease spread

As antibodies go down naturally with time after vaccine (not a glitch, that is what immune system does as can't store all these antibodies in your blood or it would be thick as glue), your memory B cells serve as blueprint to make more & T cells prevent severe disease.

So, in time of delta, the T cells are still protecting against severe disease. The antibodies have gone down with time but new ones will be made by memory B cells if they see virus but it takes TIME so mild symptomatic breakthrough can occur while those get generated to fight

And when those antibodies get generated by memory B cells (and adapt to variants no less - see paper), they (and the nasal T cells) will also bring down the virus in your nose and disable it so we should 1) culture virus before asserting
medrxiv.org/content/10.110…

as much infectivity with vaccination than without vaccination (can't go on PCR sequencing up RNA in this case because virus may have been hobbled by immune response) and; 2) perform serial viral loads to see if they come down fast due to immune response