immunologically speaking, there no rhyme or reason to believe that if 2-dose vaccine-induced neut Abs hang around for 6 months, somehow they will hang around much longer after 3rd dose. 1/
in general, it is quite unexpected that after such robust 2-dose antigen priming, as mRNA vaccine does (based on Ab titers immediately after 2nd dose), we should see such a precipitous drop in vaccine efficacy within 6 months. 2/
everyone pays attention to neut Ab titers but even NIH/Moderna's own study in lab mice showed neut Abs are not essential at all. These were confirmed in a more recent study using B cell KO mice. No Ab is needed to protect mice against #SARSCoV2.

3/
some now argue, hey, other vaccines are 3-dose vaccines too. Wait a minute, do they realize that only now? where were the same people in December 2020? I did not recall anyone saying, we need a 3-dose vaccine, not 2-dose. 4/
sure, many vaccines are 3-dose vaccines at 0, 1 month, and 6 months time. But everyone knows that but for some reason, no one even suggested running a trial for such an obvious thing. if @pfizer and @moderna_tx knew about 3-dose why not set up exactly that? 5/
I assume the 2-dose schedule came about based on neut Ab titers in initial trials. Titers were so high (compared to what we have seen in other conventional vaccines, mostly inactivated) that naturally, they thought 2-dose will be enough. 6/
sky-high Ab titers don't materialize out of blue. It needs CD4+ T cells. So, 2-dose gives a good T cell priming too. This is a reason why it is so unexpected what we are observing. 3 or 4-dose vaccine is needed to build up neut Ab titers but we got that and plus with 2-doses
7/
it is true that lab mouse is not an ideal model for the human immune system. For example, in mice, neut Ab titer stays steady after mRNA vaccination, but not in humans. 8/
the closest thing I have seen in immunology that resembles the mRNA vaccine effect is a super-antigen injection that activates specific B/T cells to such a degree that it exhausts them and they disappear leading to some kind of temporal unresponsiveness

9/

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More from @3DiMMUNE

12 Sep
I see people are still debating what is the level of protection from 2-dose vaccine against symptomatic #covid19.Enough studies now show at ~6 months post vaccination it is <50% efficacy and frequently close 0%,meaning without masks rate of infection is the same for vax/unvax 1/
but protection against severe/death is still good at 6 months (~70% efficacy).

But due to the uncertain nature of the level of Ab titers and its waning speed, immune priming or failing, and underlying conditions, is it better to wear the masks pretty much constantly outside 2/
some may ask how long should we wear the mask or social distance?

with first-generation #COVID19 vaccines, based on their efficacy, how they work, how long, it will be unrealistic to expect we could go back to pre-2020 behavior, even with 100% vaccination rates.

3/
Read 8 tweets
13 Aug
Recently, we published the concluding part III of the #SPIRAL model, which we were working on since 2016.

Pathological T Helper Polarization Requires Pre-existing Cross-Reactive Memory T Cells

I'm going to explain the significance of this model.

preprints.org/manuscript/202…
In part I published in 2018, we introduced the SPIRAL model. It proposes that cross-reactivity is the basic unit that drives the evolution of adaptive immune system and it is thymus-derived regulatory T cells, Tregs, that rely on cross-reactive epitopes to control other T cells
We also proposed that thymus-derived #Foxp3 Tregs rely on #CrossReactive epitope derived from the friendly gut microbiota to survive and function in the periphery. So one of the main roles of gut microflora is to supply #Tregs with epitopes.

onlinelibrary.wiley.com/doi/10.1111/sj…
Read 16 tweets
28 Jul
These two graphs tells the story about 3rd wave with #DeltaVariant.

daily cases vs. daily death. Based on data from 2nd wave,we should have expected already ~ 500-2000 death daily but so far the UK only reported ~ 100 daily death. Does it mean vaccine worked? No. why not?

1/
Why cannot I say with certainty that 10-20 fold lower daily deaths in the 3rd wave indicate that the vaccine is effective?

Simply because the authority consistently say that >90% of those who are diagnosed with #COVID19 are non-vaccinated.

2/
So, >90% with #COVID19 are non-vaccinated and still there is 10-20 fold fewer daily death?

This makes no sense unless #COVID19 positive population in 3rd wave is completely different from those in the 1st and 2nd waves.

3/
Read 5 tweets
28 Jan
We are entering a new, endemic stage of #COVID19 spread. Drop in efficacy (50% or less) against new SA variants is a classical example of vaccine efficacy against #influenza virus.
It is clear from all available data that both @BioNTech_Group and @moderna_tx mRNA vaccines will be less effective against SA variant and there will be many more like this.
@BioNTech_Group @moderna_tx but we will have a bigger problem than SA variant of #SARS_CoV_2. And it has to do with the little-understood phenomenon of "original antigenic sin" [OAS]. The idea that @moderna_tx or @BioNTech_Group will simply design new #mRNA #vaccines against SA variant, will not work here.
Read 6 tweets
19 Jan
In this opinion paper @RMedzhitov went back to drawing board to update his views on #allergy and how it could develop.

#immunology

I read this paper and here is my take on it

1/
@RMedzhitov Why focus on allergy? b/c allergy is a paradox. The allergy we recognize is a completely maladaptive response and has no protective role whatsoever. It is not clear why do we even need IgE

2/
@RMedzhitov So, some 10 years ago or so, @RMedzhitov started to suggest that #allergy is an intrinsic property of a certain type of #antigens, many of them with enzymatic function (enzymes). 3/
Read 24 tweets
19 Apr 20
let's talk about #CytokineStorm in #COVID19.

1st, there is no standard threshold above which something is called #CytokineStorm.

Mechanistically, the simplest form of #CytokineStorm we can understand is when anti-CD19 #CART cells are infused in tumor-bearing recipients.
in this scenario, we have large numbers of antigen-specific T cells (anti-CD19) and large numbers of antigen-bearing cells (CD19+ tumor cells). When too many T cells engage with too many antigens simultaneously in a short period of time we get #CytokineStorm
Why is that? This is because naturally developing an adaptive immune system (T cells) ordinarily doesn't work that way. 1st, for a given antigen we have very few antigen-specific T cells (~ 50 cells/antigen, unlike anti-CD19 CAR-T cells that are in millions).
Read 16 tweets

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